Retinal Dystrophy Associated With RLBP1 Retinitis Pigmentosa: A Five-Year Prospective Natural History Study.

Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation. Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments. Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period. Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.

Avoiding the Deep Plantar Arterial Arch in Transmetatarsal Amputations: A Cadaver Study.

BACKGROUND: The deep plantar arterial arch (DPAA) is formed by an anastomosis between the deep plantar artery and the lateral plantar artery. The potential risk of injury to the DPAA is concerning when performing transmetatarsal amputations, and care must be taken to preserve the anatomy. We sought to determine the positional anatomy of the DPAA based on anatomical landmarks that could be easily identified and palpated during transmetatarsal amputation. METHODS: In an effort to improve our understanding of the positional relationship of the DPAA to the distal metatarsal parabola, dissections were performed on 45 cadaveric feet to measure the location of the DPAA with respect to the distal metatarsal epiphyses. Images of the dissected specimens were digitally acquired and saved for measurement using in-house-written software. The mean, SD, SEM, and 95% confidence interval were calculated for all of the measurement parameters and are reported on pooled data and by sex. An independent-samples t test was used to assess for sex differences. Interrater reliability of the measurements was estimated using the intraclass correlation coefficient. RESULTS: The origin of the DPAA was located a mean ± SD of 35.6 ± 3.9 mm (95% confidence interval, 34.5-36.8 mm) proximal to the perpendicular line connecting the first and fifth metatarsal heads. The average interrater reliability across all of the measurements was 0.921. CONCLUSIONS: This study provides the positional relationship of the DPAA with respect to the distal metatarsal parabola. This method is easily reproducible and may assist the foot and ankle surgeon with surgical planning and approach when performing partial pedal amputation.

Imaging Biomarkers and Their Impact on Therapeutic Decision-Making in the Management of Neovascular Age-Related Macular Degeneration.

These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

Arthroscopic Evaluation of the Subtalar Joint: A Review and Survey of Pathology.

BACKGROUND: A survey of pathology present in the subtalar joint by means of subtalar arthroscopy with anterolateral and middle portals has not been extensively explored in the literature. The focus of this study was to identify pathology in the subtalar joint with subtalar joint arthroscopy using this approach. We also compared these arthroscopic findings with those reported in the literature. METHODS: We performed a retrospective review of 49 consecutive patients who had undergone 53 subtalar arthroscopic procedures. Data were obtained from intraoperative arthroscopic findings that were documented in the operative note or with arthroscopic photography. Additional procedures, including ankle arthroscopy, lateral ankle stabilization, and peroneal tendon repair, were recorded. Descriptive statistics were calculated and reported. RESULTS: Subtalar arthroscopic examination revealed that all of the patients had intra-articular synovitis or adhesions present. Twenty-two procedures (42%) demonstrated subtalar joint instability, seven (13%) revealed chondromalacia, and one (2%) had an exostosis present. These observations are consistent with other reported findings in the literature. CONCLUSIONS: This study found that the subtalar joint was most often affected by synovitis, adhesions, and instability in patients with symptomatic pathologies requiring subtalar arthroscopy. There was a relatively low incidence of chondromalacia or exostosis formation in the survey.

A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features.

Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients' hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.

Location of the Deep Plantar Artery: A Cadaveric Study.

BACKGROUND: The deep plantar (D-PL) artery originates from the dorsalis pedis artery in the proximal first intermetatarsal space, an area where many procedures are performed to address deformity, traumatic injury, and infection. The potential risk of injury to the D-PL artery is concerning. The D-PL artery provides vascular contribution to the base of the first metatarsal and forms the D-PL arterial arch with the lateral plantar artery. METHODS: In an effort to improve our understanding of the positional relationship of the D-PL artery to the first metatarsal, dissections were performed on 43 embalmed cadaver feet to measure the location of the D-PL artery with respect to the base of the first metatarsal. Digital images of the dissected specimens were acquired and saved for measurement using in-house software. Means, standard deviations, and 95% confidence intervals (CIs) were calculated for all of the measurement parameters. RESULTS: We found that the origin of the D-PL artery was located at a mean ± SD of 11.5 ± 3.9 mm (95% CI, 4.5-24.7 mm) distal to the first metatarsal base and 18.6% ± 6.5% (95% CI, 8.1%-43.4%) of length in reference to the proximal base. The average interrater reliability across all of the measurements was 0.945. CONCLUSIONS: This study helps clarify the anatomical location of the D-PL artery by providing parameters to aid the surgeon when performing procedures in the proximal first intermetatarsal space. Care must be taken when performing procedures in the region to avoid unintended vascular injury to the D-PL artery.