Bundle Defects Research Articles

Prevalence and characteristics of patent foramen ovale in a sample of Egyptian population: a computed tomography study

BackgroundThe reported prevalence of patent foramen ovale (PFO) in the general population is variable. It ranges between 8.6 and 42% according to the population studied and the imaging technique used. We aim to prospectively assess the prevalence and characteristics of PFO and interatrial septum (IAS) abnormalities as well as the related clinical manifestations in a sample of Egyptian population.ResultsThis study comprised 1000 patients who were referred for CT coronary angiography (CTCA). Mean age was 52.5 ± 10.9 years. The prevalence of PFO among the studied population was 16.3%; closed PFO (grade I) 44.2%, open PFO (grade II) 50.9%, and open PFO with jet (grade III) 4.9%. Anatomical high-risk PFO features—defined as the presence of at least 2 or more of the following (diameter ≥ 2 mm, length ≥ 10 mm, septal aneurysm “ASA”, or redundant septum)—were found in 51.5% of PFOs’ population. Other IAS abnormalities as redundant septum (8.6%), ASA (5.3%), Bachmann’s bundle (4.5%), microaneurysm (2.6%), and atrial septal defect (ASD) (0.4%) were detected. There was a lower rate of coexistence of ASA with PFO (p = 0.031). Syncope was significantly higher in patients with PFO compared to those without PFO (6.7% vs. 1.6%, p = 0.001). Stroke, transient ischaemic attacks (TIA), and dizziness were similar in both groups. TIA, dizziness, and syncope were significantly higher in patients with IAS abnormalities including PFO compared to those without IAS abnormalities. Syncope was also significantly higher in PFO with high-risk anatomical features compared to those with non-high-risk PFO population (p = 0.02).ConclusionThe prevalence of PFO in our study was approximately 16.3%, almost half of them showed anatomical high-risk features for stroke. Dizziness, syncope and TIA were significantly higher in patients with IAS abnormalities including PFO.

Retinal Nerve Fiber Layer Optical Texture Analysis and 10-2 Visual Field Assessment in Glaucoma

PurposeTo apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to 1) investigate the association between papillomacular and papillofoveal bundle defects with 10-2 visual field (VF) sensitivity abnormalities, and 2) integrate the information from RNFL bundle defect and 24-2 VF central test locations to determine the likelihood of 10-2 VF sensitivity abnormalities. DesignCross-sectional MethodsA total of 841 eyes (144 healthy, 317 glaucoma suspect, and 380 glaucoma) of 442 participants were included. Eyes underwent 24-2, and 10-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular, and papillofoveal bundles was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure–function association. ResultsPapillomacular (92.1%) and papillofoveal (37.9%) RNFL bundle defects were prevalent in eyes with glaucoma. A 10-2 VF location that was projected onto a papillomacular or a papillofoveal RNFL bundle defect had a significantly increased likelihood of reduced sensitivity (ORs of 18.61 at PDP < 5%, and 20.17 at TDP < 5%, respectively, P < 0.001 for both). When predicting the likelihood of VF abnormality in a 10-2 test location, noticeably higher odds ratios were observed when overlapping with an RNFL bundle defect, compared to when an abnormal corresponding 24-2 central point was present. ConclusionsPapillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with glaucoma. When detected, they significantly increase the likelihood of abnormality in the corresponding central VF test locations assessed by the 10-2 test.

Post-fever Retinitis With a Positive Weil-Felix Test: A Study From a Tertiary Center in South India.

Background Post-fever retinitis (PFR) is reported two to six weeks after fever and affects one or both eyes. Rickettsial fever is one of the most common causes of PFR. This study aimed to report the clinical features and treatment outcomes of PFR cases with a positive Weil-Felix test. Methodology In this study, we collected demographic data, fever details, eye symptoms, ocular examination findings, optical coherence tomography (OCT) and fundus fluorescein angiography findings, laboratory findings, and length of follow-up of consecutive PFR cases with a positive Weil-Felix test. All cases were treated with oral doxycycline and prednisolone. Final best-corrected visual acuity (BCVA) and ocular examination findings were recorded. Visual field examination and follow-up OCT results were noted if available. Results A total of nine patients (eight males) with a mean age of 39.1 years with fever before ocular symptoms and positive Weil-Felix test were included.Six patients had bilateral disease. The mean initial and final BCVA in the affected eyes was 1.16 and 0.35 logMAR units, respectively (p < 0001). All 15 eyes had typical white retinitis patches and retinal hemorrhages which resolved after treatment. OCT showed hyperreflectivity and inner retinal disorganization over retinitis patches. White subretinal lines were noted in three patients and retinal nerve fiber bundle defect with corresponding visual field defect was seen in one eye. Conclusions In this study, PFR due to rickettsia infections has been reported from our region for the first time. Hence, eye specialists in the region should be aware of this entity.

Papillomacular bundle defect (PMBD) in glaucoma patients with high myopia: frequency and risk factors

Little is known about the papillomacular bundle defect (PMBD) in glaucoma. As such, we investigated the frequency of PMBD in glaucoma patients with high myopia, and its risk factors. In this retrospective, cross-sectional study, retinal nerve fiber layer (RNFL) defect was analyzed in 92 glaucomatous eyes with high myopia (axial length of 26.0 mm or more or an average spherical value of − 6.0 diopters or less). After dividing them into two groups with and without PMBD, the clinical characteristics of the groups were compared and analyzed. The mean age of the patients was 52.1 ± 10.5 years, and there were 53 males and 39 females. PMBD were observed in 55 eyes (59.8%). There was no significant intergroup difference in baseline or follow-up intraocular pressure (IOP). Parapapillary atrophy (PPA)-to-disc-area ratio (OR 3.83, CI: 1.58–10.27, p = 0.010), lamina cribrosa defect (LCD; OR 2.92, CI: 1.14–8.13, p = 0.031) and central visual field defect (CVFD; OR 3.56, CI: 1.38–9.58, p = 0.010) were significantly associated with the PMBD..

Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension

To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results. Cross-sectional study. Six hundred eyes of 306 patients with OHT. All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis. Prevalence of RNFL defects. The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 μm and 568.8 ± 31.2 μm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects. A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Low-temperature radiation damage studies in single-walled carbon nanotube bundles by hopping conductance

The paper shows the results of studying radiation defects in single-walled carbon nanotube bundles at low temperatures. The data were obtained in a unique experiment that inseparably combines 1 MeV electron irradiation at a temperature of ∼10 K and electrical conductivity measurements over a wide temperature range of 5–300 K. The experiment allowed us to reveal and separate the influence of stable and unstable radiation defects on the electrical properties of SWCNTs. It is shown that the 2D Mott variable range hopping conduction regime exhibits resistance to electron irradiation. The hopping conductivity is the dominant charge transfer mechanism in the temperature range of 5–50 K in both the pristine and irradiated SWCNT samples. It was found that the parameters of hopping transport demonstrate high sensitivity to the introduction and annealing of radiation defects. The low-temperature electron irradiation revealed the possibility of the emergence of an additional conduction channel in the irradiated SWCNTs. This channel demonstrates thermally activated behavior with a low activation energy of ∼0.5 meV at temperatures of 5–50 K. The obtained data indicate that unstable radiation defects create conditions for the possibility of impurity band conduction in SWCNT bundles.

Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles.

Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of Kiaa1024L/Minar2, a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of kiaa1024L/minar2 causes hearing loss in the zebrafish. Defects in mechanotransduction, longer and thinner hair bundles, and enlarged apical lysosomes in hair cells are observed in the kiaa1024L/minar2 mutant. In cultured cells, Kiaa1024L/Minar2 is mainly localized to lysosomes, and its overexpression recruits cholesterol and increases cholesterol labeling. Strikingly, cholesterol is highly enriched in the hair bundle membrane, and loss of kiaa1024L/minar2 reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the kiaa1024L/minar2 mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing.

Clinical application of multicolor imaging in Leber hereditary optic neuropathy.

To characterize features of retinal never fiber in Leber Hereditary Optic Neuropathy (LHON) using multicolor (MC) imaging and color fundus photography (CFP). Ninety-two eyes of patients with LHON underwent MC imaging, optic disc spectral domain optical coherence tomography (SD-OCT), and CFP. Two independent observers graded RNFL visibility scores and two other experts determined never fiber bundle defects from four-quadrant readings. CFP, standard MC, infrared reflectance (IR), green reflectance (GR), blue reflectance (BR), and green-blue-enhanced (BG) imaging were compared. Agreement on never fiber bundle defects was substantial for CFP, standard MC, GR, BR, and BG images relative to IR. It was shown that BR (2.71 ± 0.55) had the best mean RNFL visibility score, BG (2.69 ± 0.52), GR (2.69 ± 0.56), standard MC (2.04 ± 0.79), CFP (1.80 ± 0.82), and IR (0.45 ± 0.59) followed. Agreement on temporal area defects was relatively improved. Youden's indices for CFP (78.21%), standard MC (84.48%), GR (90.92%), BR (89.64%), and BG (90.99%) indicated good detection of defects in the papillomacular bundle (PMB)/ high suspicion of patients with LHON, particularly for BG and GR. According to the proportion of never fiber bundle defects, standard MC, GR, BR, and BG can roughly determine the LHON clinical stage, especially in subacute and chronic stages, and standard MC is superior for patients with LHON of all stages. The stage judged by MC was consistent with the course inferred by pRNFL thickness. As an adjunct to SD-OCT, the MC image, particularly the GR and BG can delineate RNFL more effectively than CFP. The MC image may be a useful adjunct to OCT for detecting or monitoring never fiber bundle defects, providing inexpensive and rapid methods that can quickly identify patients with high suspicion of LHON.

Ancillary PanoMap OCT shows the progression of glaucomatous papillomacular bundle defect with disc haemorrhage on the fovea–disc axis

Background/aimsTo identify the spatial relationship between disc haemorrhage (DH) on the fovea–disc axis and retinal nerve fibre layer (RNFL) defect in the papillomacular bundle (PMB) using ancillary PanoMap optical coherence...

Concordance of Objectively Detected Retinal Nerve Fiber Bundle Defects in En Face OCT Images with Conventional Structural and Functional Changes in Glaucoma

To assess how objectively detected defects in retinal nerve fiber bundle (RNFB) reflectance on en face OCT images relate to circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and visual field defects. Cross-sectional study. Sixteen participants with early glaucoma and 29 age-matched healthy controls, of whom 22 had usable en face images for the establishment of normative levels of RNFB reflectance. All the participants underwent cpRNFLT scans, visual field examination, and wide-field OCT. En face reflectivity was assessed objectively using the Summary of Multiple Anatomically Adjusted Slabs method. En face defects were deemed concordant with cpRNFLT when they had at least 1 cpRNFLT point with P < 0.01, within ± 15° of the predicted insertion on the optic disc. Visual fields were examined using custom suprathreshold perimetry and SITA Standard 24-2. For each visual field location, the corresponding reflectance was deemed abnormal if any en face superpixel within ± 1° was abnormal. The overall, positive, and negative agreements were measured in each participant. Proportion of concordant defects between en face reflectance analysis and cpRNFLT (%) as well as overall, positive, and negative agreements between en face reflectance analysis and visual field results. Most en face abnormalities had concordant cpRNFLT defects in the mapped sector (median proportion concordant, 0.85; interquartile range, 0.74-0.95). In eyes with glaucoma, a median of 8.1% (range, 2.4%-23.7%) and 14.9% (range, 3.5%-29.1%) locations showed corresponding en face and visual field defects using 24-2 and custom perimetry, respectively. Both the perimetric strategies had moderate-to-good raw agreement with en face analysis (0.66-0.68), with stronger agreement on normal findings than on defects (0.77-0.78 and 0.4-0.44). Objectively extracted reflectance defects showed strong concordance with conventional cpRNFLT damage and good agreement with perimetry, which could be enhanced by further minimization of image artifacts.

Visual Field Defect Patterns Associated With Lesions of the Retrochiasmal Visual Pathway.

Perimetry is widely used in the localization of retrochiasmal visual pathway lesions. Although macular sparing, homonymous paracentral scotomas, and quadrantanopias are regarded as features of posterior retrochiasmal visual pathway lesions, incongruous hemianopia is regarded as a hallmark of anterior lesions. Recent studies have questioned the specificity of these defect patterns. Retrospective record review conducted in a single, academic, medical center using an electronic search engine with the terms ""homonymous hemianopia," "optic tract," "temporal lobectomy," "visual field defect," and "MRI." Patients were included if they had reliable, automated, static visual fields, high-quality reviewable MRI scans, and pertinent lesions. MRI lesions were assigned to 1 of 6 retrochiasmal visual pathway segments by the study neuroradiologist. Two study authors independently reviewed the visual fields and designated 10 different defect patterns. From an original cohort of 256 cases, only 83 had MRI-defined lesions that were limited to particular retrochiasmal segments and had visual field defect patterns that allegedly permitted localization to those particular segments. The 5 contralateral nerve fiber bundle defects were exclusive to optic tract tumors with rostral extension. Pie-in-the-sky defects were exclusive to Meyer loop lesions. Among 22 fields with macular sparing, 86% arose from the visual cortex or posterior optic radiations. Among 31 fields with homonymous quadrantanopias, 77% arose from Meyer loop, visual cortex, or posterior optic radiations. Among 13 fields with homonymous paracentral scotomas, 69% arose from visual cortex or posterior optic radiations. Optic tract lesions accounted for 70% of incongruous hemianopias but that pattern occurred uncommonly. In correlating discrete MRI-defined retrochiasmal lesions with visual field defect patterns identified on static perimetry, this study showed that macular sparing, homonymous paracentral scotomas, and quadrantanopias localized to the visual cortex and posterior optic radiations segments but not exclusively. It has differed from an earlier study in showing that incongruous hemianopias occur predominantly from optic tract lesions.

Case of Legal Blindness Secondary to Optic Nerve Head Drusen

Optic nerve head drusen are relatively infrequent abnormalities of the optic disc that are usually discovered as incidental findings during a routine eye examination. While typically considered to be benign, visual field loss due to the drusen is not uncommon. Visual field defects are more prevalent in superficial drusen than buried drusen, and can present as nerve fiber bundle defects, generalized concentric constriction, or enlargement of the blind spot. The extent of damage is variable, but it is rare that the degree of field loss leads to substantial functional impairment. This case presents a patient with significant bilateral concentric field loss secondary to optic nerve drusen that caused severe visual impairment and disability.

Retinal Nerve Fiber Layer Optical Texture Analysis: Involvement of the Papillomacular Bundle and Papillofoveal Bundle in Early Glaucoma

To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) in eyes with early glaucoma to investigate (1) the pattern of RNFL defects, (2) how often the papillomacular bundle and papillofoveal bundles are involved, and (3) the association between papillomacular and papillofoveal bundle defects and visual field (VF) sensitivity abnormalities. Cross-sectional study. Two hundred four eyes with early glaucoma (VF mean deviation, ≥ -6 dB) with RNFL defects from 171 consecutively enrolled patients with glaucoma. All eyes underwent 24-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate bundle, papillomacular bundle (i.e., bundles from the macula, excluding the fovea), and papillofoveal bundle (i.e., bundles from the fovea) was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association. Proportions of eyes with papillomacular or papillofoveal bundle defects. Of the 204 eyes, 71.6% and 17.2% demonstrated RNFL defects involving the papillomacular and papillofoveal bundles, respectively; 25.0% showed arcuate bundle defects without involvement of papillomacular or papillofoveal bundles. The pattern of RNFL defects was diverse; the most common was concomitant involvement of the inferior arcuate bundle and the inferior papillomacular bundle (20.6%). Papillomacular or papillofoveal bundle defects were not associated with VF defects (i.e., with ≥ 3 contiguous locations with abnormal VF sensitivity in the pattern deviation probability plot) in the corresponding hemifield, although VF sensitivity of any 1 of the central 4 VF locations of the 24-2 test, which were within the macula, was more likely to be abnormal (P < 0.05 in the pattern deviation probability plot; odds ratio, 12.5; 95% confidence interval, 7.0-22.5) when the VF stimulus was projected onto a papillomacular or papillofoveal bundle defect than that projected onto an intact papillomacular or papillofoveal bundle. Contrary to the conventional notion that the fovea and macula are not affected until the late stages of glaucoma, papillofoveal and papillomacular bundle defects were common in early glaucoma, and they were associated with central VF sensitivity loss at the corresponding VF test locations.

Normal Tension Glaucoma

Normal tension glaucoma (NTG) is a subvariant of primary open angle glaucoma (POAG) or a separate entity. NTG is defined as chronic open angle glaucoma without elevated intraocular pressure or normal intraocular pressure. Normal intraocular pressure is between 10 and 21 mmHg and is defined as two times the standard deviation of the mean intraocular pressure in the normal population. In addition to the absence of elevated intraocular pressure, all the classic symptoms of glaucoma are otherwise present. These include a conspicuous glaucomatous optic disc excavation, nerve fibre bundle defects, and corresponding visual field defects. Papillary rim haemorrhages are frequently found. The visual field defects in NDG are usually more central compared to POAG and are therefore described as more disturbing by the patient. The anterior chamber angle is open and there are no other changes suggestive of secondary glaucoma (pigment dispersion, pseudo-exfoliation). The exact pathophysiology of NDG is not well understood. Pathophysiologically, circulatory disturbances in the sense of arterial hypo- as well as hypertension may play an essential role or at least increase the susceptibility of the optic nerve to intraocular pressure fluctuations as well as blood pressure dips. Therefore, this requires not only a purely ophthalmologic but also interdisciplinary treatment of the patient with confirmed NDG. The primary goal of treatment is the reduction of intraocular pressure, which can stop the disease. This article gives an overview of epidemiology, aetiology, clinical findings and therapies.

Yield of investigations in patients with questionable nonglaucomatous optic neuropathy

ObjectifLa neuropathie optique non glaucomateuse (NONG) peut souvent être diagnostiquée à tort comme un glaucome à pression normale (GPN). Il est important de faire la distinction entre ces deux affections pour ce qui est de choisir le traitement, d’établir le pronostic et de déterminer le besoin d'examens plus approfondis. Nous présentons ici les caractéristiques d'une cohorte de patients qui nous avaient été adressés en vue d'une consultation neuro-ophtalmologique afin de faire la distinction entre la neuropathie optique glaucomateuse (NOG) et la NONG. MéthodesAnalyse rétrospective des dossiers de patients qui ont été examinés en raison d'une NOG par opposition à une NONG entre 2018 et 2020 dans une clinique de soins tertiaires de neuro-ophtalmologie. Les patients ont reçu un diagnostic de NOG ou de NONG en fonction du degré de pâleur du disque optique, du degré d'excavation papillaire et de l'acuité visuelle centrale, et/ou lorsque les examens ont mis au jour une cause de NONG. RésultatsSur les 83 patients admis à l’étude, on a jugé que 71 patients (86 %) présentaient une NONG possible après l'examen initial et la neuro-imagerie. De ce nombre, on a conclu que 14 patients (19,7 %) présentaient effectivement une NONG et que 7 patients (9,9 %) présentaient à la fois une NOG et une NONG. Voici les causes les plus fréquentes de NONG : causes indéterminées (8), antécédents de névrite optique (4) et conflit neurovasculaire (2). La neuro-imagerie n'a pas donné beaucoup de résultats : des anomalies ont été observées chez seulement 4 des 71 patients (5,6 %). Aucun cas d'excavation bilatérale en l'absence de déficit pupillaire afférent relatif (DPAR) ne s'accompagnait d'anomalies à l'imagerie; de même, aucun des patients chez lesquels on a noté des anomalies à l'imagerie n'a eu besoin d'une intervention. La pression intraoculaire et le rapport cupule/disque des patients qui présentaient une NONG étaient plus faibles, et chez la plupart de ceux-ci (86 %), on notait une pâleur du disque optique. Les anomalies des faisceaux de fibres nerveuses étaient plus fréquentes tant dans la NOG que la NONG, les anomalies nasales étant plus fréquentes en présence de NOG. ConclusionsLorsque la NONG imite la NOG, la cause sous-jacente est souvent inconnue, et les résultats obtenus à la neuro-imagerie sont peu probants. L'intérêt d'examiner les patients qui présentent une excavation bilatérale sans DPAR afin de mettre au jour une NONG est particulièrement faible.

Flow-Through Arterialized Posterior Interosseous Nerve Grafts for Digital Neurovascular Bundle Defects: Anatomical Study

Digital neurovascular bundle defects are often encountered during crush or avulsion injuries and require complex reconstruction. Use of an arterialized nerve graft (neurovascular graft) serving both as an interpositional arterial conduit and as a nerve graft could be a reconstructive option in these cases. In this anatomical study, the authors aimed to describe a neurovascular graft of the posterior interosseous nerve and a branch of the anterior interosseous artery for neurovascular bundle reconstruction of the fingers. Eighteen forearms were injected with red latex in order to collect the anatomical characteristics of the posterior interosseous nerve and the artery running near it. In all cases, the posterior interosseous nerve was followed by a branch of the anterior interosseous artery: the distal dorsal branch of the anterior interosseous nerve. The origin of this artery was proximal to the radiocarpal joint, at an average of 56.5 ± 11.1 mm. The proximal and distal diameters of the branch of the anterior interosseous artery were 1.6 ± 0.2 and 1.1 ± 0.2 mm, respectively. The proximal and distal diameters of the posterior interosseous nerve were 1.2 ± 0.3 mm and 1.1 ± 0.3 mm, respectively. These results show that a potential free neurovascular graft using the posterior interosseous nerve as nerve graft and the anterior interosseous artery as an arterial bypass to reconstruct both the nerve and arterial tree of the finger could be a useful approach. The authors speculate that this graft could be used to reconstruct the neurovascular bundle of amputated or devascularized digits.

Enhanced Objective Detection of Retinal Nerve Fiber Bundle Defects in Glaucoma With a Novel Method for En Face OCT Slab Image Construction and Analysis.

PurposeTo introduce and evaluate the performance in detecting glaucomatous abnormalities of a novel method for extracting en face slab images (SMAS), which considers varying individual anatomy and configuration of retinal nerve fiber bundles.MethodsDense central retinal spectral domain optical coherence tomography scans were acquired in 16 participants with glaucoma and 19 age-similar controls. Slab images were generated by averaging reflectivity over different depths below the inner limiting membrane according to several methods. SMAS considered multiple 16 µm thick slabs from 8 to 116 µm below the inner limiting membrane, whereas 5 alternative methods considered single summary slabs of various thicknesses and depths. Superpixels in eyes with glaucoma were considered abnormal if below the first percentile of distributions fitted to control data for each method. The ability to detect glaucoma defects was measured by the proportion of abnormal superpixels. Proportion of superpixels below the fitted first percentile in controls was used as a surrogate false-positive rate. The effects of slab methods on performance measures were evaluated with linear mixed models.ResultsThe ability to detect glaucoma defects varied between slab methods, χ2(5) = 120.9, P < 0.0001, with SMAS showing proportion of abnormal superpixels 0.05 to 0.09 greater than alternatives (all P < 0.0001). No slab method found abnormal superpixels in controls.ConclusionsSMAS outperformed alternatives in detecting abnormalities in eyes with glaucoma. SMAS evaluates all depths with potential retinal nerve fiber bundle presence by combining multiple slabs, resulting in greater detection of reflectance abnormalities with no increase in surrogate false positives.Translational RelevanceSMAS may be used to objectively detect glaucoma defects in en face optical coherence tomography images.

Phenotypic differences in the inner ears of CBA/CaJ and C57BL/6J mice carrying missense and single base pair deletion mutations in the Cdh23 gene.

Different mutations in the cadherin 23 (CDH23) gene in different genetic backgrounds have been linked to either syndromic or nonsyndromic forms of deafness in humans. We previously reported a progressive hearing loss (HL) mouse model, the Cdh23erl/erl mouse, which carries a 208T > C mutation causing an amino acid substitution at S70P in C57BL/6J mice. To investigate the differences in Cdh23 mutation-related HL in different genetic backgrounds, we used the CRISPR/Cas9 system to generate homozygous mice in the CBA/CaJ background that have the same base pair missense mutation (208T > C) (Cdh23erl2/erl2 ) as Cdh23erl/erl mice in the C57BL/6J background or a single base pair deletion (235G) (Cdh23V2J2/V2J2 ) in the Cdh23 gene at exon 5. The two mutant mice exhibit hearing impairment across a broad range of frequencies. The progression of HL in Cdh23erl2/erl2 mice is slower than that in Cdh23erl/erl mice. We also found structural abnormalities in the stereocilia of cochlear hair cells in Cdh23erl2/erl2 and Cdh23V2J2/V2J2 mice. Cdh23V2J2/V2J2 mice show signs of vestibular dysfunction in open field behavior and swimming tests. In addition, we observed hair bundle defects in vestibular hair cells in Cdh23V2J2/V2J2 mice. Our results suggest an interaction between the erl locus and the C57BL/6J background that exacerbates HL in Cdh23erl/erl mice. Moreover, our study confirms that the Cdh23 gene is essential for normal hearing and balance. These two novel mutant mouse strains provide excellent models for studying CDH23 mutation-related deafness in humans.

A Novel Stimulus to Improve Perimetric Sampling within the Macula in Patients with Glaucoma.

SIGNIFICANCEIdentifying glaucomatous damage to the macula has become important for diagnosing and managing patients with glaucoma. In this study, we presented an approach that provides better perimetric sampling for the macular region, by testing four locations, with a good structure-function agreement.PURPOSEWe previously presented a basis for customizing perimetric locations within the macula. In this study, we aimed to improve perimetric sampling within the macula by presenting a stimulus at four locations, with maintaining a good structure-function agreement.METHODSWe tested one eye each of 30 patients (aged 50 to 88 years). Patients were selected based on observed structural damage to the macula, whereas perimetric defect (using 24-2) did not reflect the locations and extent of this damage. We used en face images to visualize retinal nerve fiber bundle defects. To measure perimetric sensitivities, we used a blob stimulus (standard deviation of 0.25°) at the 10-2 locations. A perimetric defect for a location was defined as any value equal to or deeper than −4, −5, and −6 dB below the mean sensitivity for 37 age-similar controls (aged 47 to 78 years). We also presented an elongated sinusoidal stimulus for 20 patients at four locations within the macula, in which we defined a perimetric defect as any value below the 2.5th percentile from controls.RESULTSThe −4, −5, and −6 dB criteria identified perimetric defects in 14, 13, and 11 patients, respectively. When testing with the elongated stimulus, 18 patients were identified with perimetric defect. The perimetric defects were consistent with the structural damage.CONCLUSIONSThe elongated stimulus showed a good structure-function agreement with only four testing locations as compared with 68 locations used with the blob stimulus. This demonstrates a clinical potential for this new stimulus in the next generation of perimetry.

Long noncoding RNA regulation of spermatogenesis via the spectrin cytoskeleton in Drosophila.

The spectrin cytoskeleton has been shown to be critical in diverse processes such as axon development and degeneration, myoblast fusion, and spermatogenesis. Spectrin can be modulated in a tissue specific manner through junctional protein complexes, however, it has not been shown that long noncoding RNAs (lncRNAs) interact with and modulate spectrin. Here, we provide evidence of a lncRNA CR45362 that interacts with α-Spectrin, is required for spermatid nuclear bundling during Drosophila spermatogenesis. We observed that CR45362 showed high expression in the cyst cells at the basal testis, and CRISPR-mediated knockout of CR45362 led to sterile male, unbundled spermatid nuclei, and disrupted actin cones. Through chromatin isolation by RNA precipitation—mass spectrometry (ChIRP-MS), we identified actin-spectrin cytoskeletal components physically interact with the lncRNA CR45362. Genetic screening on identified cytoskeletal factors revealed that cyst cell-specific knockdown of α-Spectrin phenocopied CR45362 mutants and resulted in spermatid nuclear bundle defects. Consistently, CR45362 knockout disrupted the co-localization of α-Spectrin and spermatid nuclear bundles in the head cyst cells at the basal testis. Thus, we uncovered a novel lncRNA CR45362 that interacts with α-Spectrin to stabilize spermatid nuclear bundles during spermatid maturation.