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American Journal of Ophthalmology Jun 2024Exfoliation syndrome (XFS) is a systemic connective tissue disorder with elusive pathophysiology. We hypothesize that a mouse model with elastic fiber defects caused by...
PURPOSE
Exfoliation syndrome (XFS) is a systemic connective tissue disorder with elusive pathophysiology. We hypothesize that a mouse model with elastic fiber defects caused by lack of lysyl oxidase like 1 (LOXL1 encoded by Loxl1), combined with microfibril deficiency due to Fbn1 mutation (encoding fibrillin-1, Fbn1) will display ocular and systemic phenotypes of XFS.
METHODS
Loxl1 was crossed with Fbn1 to create double mutant (dbm) mice. Intraocular pressure (IOP), visual acuity (VA), electroretinogram (ERG) and biometry were characterized in 4 genotypes (wt, Fbn1, Loxl1, dbm) at 16 weeks old. Optic nerve area was measured by ImageJ and axon counting was achieved by AxonJ. Deep whole-body phenotyping was performed in wt and dbm mice. Two-tailed Student's t-test was used for statistical analysis.
RESULTS
There was no difference in IOP between the 4 genotypes. VA was significantly reduced only in dbm mice. The majority of biometric parameters showed significant differences in all 3 mutant genotypes compared to wt, and dbm had exacerbated anomalies compared to single mutants. Dbm mice showed reduced retinal function and significantly enlarged ON area when compared with wt. Dbm mice exhibited severe systemic phenotypes related to abnormal elastic fibers, such as pelvic organ prolapse, cardiovascular and pulmonary abnormalities.
CONCLUSIONS
Ocular and systemic findings in dbm mice support functional overlap between fibrillin-1 and LOXL1, two prominent components of exfoliation material. Although no elevated IOP or reduction of axon numbers was detected in dbm mice at 16-week-old, their reduced retinal function and enlarged ON area indicate early retinal ganglion cell dysfunction. Dbm mice also provide insight on the link between XFS and systemic diseases in humans.
PubMed: 38909741
DOI: 10.1016/j.ajo.2024.06.015 -
Experimental Eye Research Jun 2024The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's... (Review)
Review
The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma.
PubMed: 38906240
DOI: 10.1016/j.exer.2024.109975 -
Frontiers in Nutrition 2024Although numerous studies have substantiated the neuroprotective effects of vitamin B on the optic nerve and its enhancement of visual function, comprehensive data...
OBJECTIVE
Although numerous studies have substantiated the neuroprotective effects of vitamin B on the optic nerve and its enhancement of visual function, comprehensive data delineating the correlation between vitamin B and glaucoma at a national demographic scale remain insufficient. This study is designed to explore the link between the dietary consumption of vitamin B and glaucoma.
METHODS
This study included 3,850 individuals aged 40 and older from the National Health and Nutrition Examination Survey (NHANES), spanning 2005-2008. Dietary consumption of vitamin B was calculated from the average of two 24-h dietary recall interviews. Glaucoma was diagnosed in accordance with the established Rotterdam criteria. To evaluate the relationship between vitamin B dietary consumption and the risk of glaucoma, we employed Restricted Cubic Splines and weighted multivariable logistic regression analysis. We employed stratified and three other sensitivity analyses to confirm the robustness of our results, and conducted a preliminary exploration of the potential association between vitamin B supplement consumption and glaucoma risk.
RESULTS
After adjusting for covariates, we found a significant inverse correlation between dietary consumption of vitamin B and glaucoma risk ( = 0.18; for trend = 0.02). Stratified analysis and three other sensitivity analyses revealed stability in the outcomes (all p for interaction>0.05). Compared to the lowest quartile of consumption (≤1.23 mg/day), individuals in the highest quartile of vitamin B consumption (>2.34 mg/day) experienced a 75% reduction in glaucoma risk (OR = 0.25, 95% CI 0.07-0.92). However, the effect of vitamin B supplements on glaucoma was inconclusive.
CONCLUSION
A diet high in vitamin B inversely correlates with glaucoma risk, suggesting that increasing dietary intake of vitamin B could be a viable preventative strategy against glaucoma among adults in the United States.
PubMed: 38903614
DOI: 10.3389/fnut.2024.1363539 -
Indian Journal of Anaesthesia Jun 2024
PubMed: 38903256
DOI: 10.4103/ija.ija_205_24 -
American Journal of Ophthalmology Jun 2024To evaluate ophthalmological, neurological, radiological, and laboratory data in patients with multiple sclerosis (MS) and to identify new ophthalmological factors that...
PURPOSE
To evaluate ophthalmological, neurological, radiological, and laboratory data in patients with multiple sclerosis (MS) and to identify new ophthalmological factors that could be helpful as biomarkers of the disease, potentially leading to an earlier prediction of disease course and disability progression.
DESIGN
Retrospective, cross-sectional-study.
METHODS
Best-corrected visual acuity (BCVA), ophthalmological biomicroscopy of the anterior segment and fundus, structural optical coherence tomography (OCT) with retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), and OCT Angiography (OCTA) with vascular density (VD) were performed. The following clinical and neuro-radiological features were assessed: MS phenotype, disease duration, clinical severity, type of treatment, and T2-weighted lesion load plus T1-weighted Gd+-enhancing lesion number on the last brain and spinal cord MRI.
RESULTS
One hundred and six patients (212 eyes) were analyzed. Sixty-six of them (62.2 %) had MS and 40 (37.8%) were matched healthy controls (HCs). patients with MS showed lower RNFL, GCC, and VD in the radial peripapillary capillary plexus than controls in both eyes (p<0.05). By Performing a logistic regression with a distinct MS outcome for both eyes, we were able to demonstrate that the value that was most predictive of MS was the average GCC thickness (p=0.009). Regression analysis demonstrated that patients with a higher T2-weighted lesions showed a lower RNFL thickness value and reduced GCC and VD values than those with a low lesion load (p<0.01 and p<0.05, respectively). Similarly, relapsing MS patients showed lower RNFL values (p<0.05).
CONCLUSIONS
Several OCT- and OCTA-optic nerve parameters could be useful prognostic biomarkers for the MS disease course in clinical practice. However, it is necessary to do additional research with larger sample sizes in order to validate these findings.
PubMed: 38901720
DOI: 10.1016/j.ajo.2024.06.011 -
Radiotherapy and Oncology : Journal of... Jun 2024In intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon...
OBJECTIVE
In intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon therapy. High-energy pristine transmission ('shoot through') pencil beams have no Bragg peak in the patient, but show a sharp lateral penumbra at the target level. We investigated whether combining Bragg peaks with Transmission pencil beams('IMPT&TPB') could improve head-and-neck plans by exploiting the steep lateral dose fall-off of transmission pencil beams.
APPROACH
Our system for automated multi-criteria IMPT plan optimisation was extended for combined optimisation of BPs and TPBs. The system generates for each patient a Pareto-optimal plan using a generic 'wish-list' with prioritised planning objectives and hard constraints. For eight nasopharynx cancer patients (NPC) and eight oropharynx cancer (OPC) patients, the IMPT&TPB plan was compared to the competing conventional IMPT plan with only Bragg peaks, which was generated with the same optimiser, but without transmission pencil beams.
MAIN RESULTS
Clinical OAR and target constraints were met in all plans. By allowing transmission pencil beams in the optimisation, on average 14 of the 25 investigated OAR plan parameters significantly improved for NPC, and 9 of the 17 for OPC, while only one OPC parameter showed small but significant deterioration. Non-significant differences were found in the remaining parameters. In NPC, cochlea Dmean reduced by up to 17.5 Gy and optic nerve D by up to 11.1 Gy.
CONCLUSION
Compared to IMPT, IMPT&TPB resulted in comparable target coverage with overall superior OAR sparing, the latter originating from steeper dose fall-offs close to OARs.
PubMed: 38897315
DOI: 10.1016/j.radonc.2024.110388 -
International Journal of Ophthalmology 2024To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD).
AIM
To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD).
METHODS
A total of 33 patients with NMOSD treated with inebilizumab (Group INB, =15) or rituximab (Group RTX, =18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.
RESULTS
Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (<0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio (<0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy (<0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy (>0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections.
CONCLUSION
The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.
PubMed: 38895668
DOI: 10.18240/ijo.2024.06.12 -
BioRxiv : the Preprint Server For... Jun 2024Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in , increases axon regeneration in injured neurons that show spontaneous...
Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in , increases axon regeneration in injured neurons that show spontaneous regeneration. Inhibition of G3BP1 by expression of its acidic or 'B-domain' accelerates axon regeneration after nerve injury bringing a potential therapeutic intervention to promote neural repair in the peripheral nervous system. Here, we asked if G3BP1 inhibition is a viable strategy to promote regeneration in the injured mammalian central nervous system where axons do not regenerate spontaneously. G3BP1 B-domain expression was found to promote axon regeneration in both the mammalian spinal cord and optic nerve. Moreover, a cell permeable peptide to a subregion of G3BP1's B-domain (rodent G3BP1 amino acids 190-208) accelerated axon regeneration after peripheral nerve injury and promoted the regrowth of reticulospinal axons into the distal transected spinal cord through a bridging peripheral nerve graft. The rodent and human G3BP1 peptides promoted axon growth from rodent and human neurons cultured on permissive substrates, and this function required alternating Glu/Asp-Pro repeats that impart a unique predicted tertiary structure. These studies point to G3BP1 granules as a critical impediment to CNS axon regeneration and indicate that G3BP1 granule disassembly represents a novel therapeutic strategy for promoting neural repair after CNS injury.
PubMed: 38895344
DOI: 10.1101/2024.06.07.597743 -
Diagnostics (Basel, Switzerland) May 2024In order to generate a machine learning algorithm (MLA) that can support ophthalmologists with the diagnosis of glaucoma, a carefully selected dataset that is based on...
In order to generate a machine learning algorithm (MLA) that can support ophthalmologists with the diagnosis of glaucoma, a carefully selected dataset that is based on clinically confirmed glaucoma patients as well as borderline cases (e.g., patients with suspected glaucoma) is required. The clinical annotation of datasets is usually performed at the expense of the data volume, which results in poorer algorithm performance. This study aimed to evaluate the application of an MLA for the automated classification of physiological optic discs (PODs), glaucomatous optic discs (GODs), and glaucoma-suspected optic discs (GSODs). Annotation of the data to the three groups was based on the diagnosis made in clinical practice by a glaucoma specialist. Color fundus photographs and 14 types of metadata (including visual field testing, retinal nerve fiber layer thickness, and cup-disc ratio) of 1168 eyes from 584 patients (POD = 321, GOD = 336, GSOD = 310) were used for the study. Machine learning (ML) was performed in the first step with the color fundus photographs only and in the second step with the images and metadata. Sensitivity, specificity, and accuracy of the classification of GSOD vs. GOD and POD vs. GOD were evaluated. Classification of GOD vs. GSOD and GOD vs. POD performed in the first step had AUCs of 0.84 and 0.88, respectively. By combining the images and metadata, the AUCs increased to 0.92 and 0.99, respectively. By combining images and metadata, excellent performance of the MLA can be achieved despite having only a small amount of data, thus supporting ophthalmologists with glaucoma diagnosis.
PubMed: 38893600
DOI: 10.3390/diagnostics14111073 -
Cancers Jun 2024Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical...
Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical strategies through a review of medical records from 80 patients who underwent surgical resection at the University of Naples Federico II. Different surgical approaches were employed based on the tumor's location relative to the optic nerve's long axis, categorized into lateral (type I), medial (type II), and diffuse (type III). We examined clinical, neuroradiological, surgical, pathological, and outcome factors. Proptosis emerged as the most frequent symptom (97%), followed by visual impairment (59%) and ocular motility issues (35%). Type I represented 20%, type II 43%, and type III 17%. Growth primarily affected the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%). The resection outcomes varied, with Simpson grades I and II achieved in all type I cases, 67.5% of type II, and 18% of type III. Recurrence rates were highest in type II (41.8%) and type III (59%). Improvement was notable in proptosis (68%) and visual function (51%, predominantly type I). Surgery for spheno-orbital meningiomas should be tailored to each patient, considering individual characteristics and tumor features to improve quality of life by addressing primary symptoms like proptosis and visual deficits.
PubMed: 38893267
DOI: 10.3390/cancers16112148