Clinical Outcomes in Scleral Fixation Secondary Intraocular Lens with Yamane versus Suture Techniques: A Systematic Review and Meta-Analysis.

Background: The purpose of the study is to compare the visual outcomes and complications of sutured scleral fixation (SSF), a traditional and conservative surgical approach, and the newer and faster Yamane technique for secondary intraocular lens placement. Methods: A literature search was performed on PubMed, Embase, and Scopus on studies published between 1 July 2017 to 29 September 2023. Outcomes analyzed included the final best corrected visual acuity (BCVA) between 3 and 12 months to assess the effectiveness of the procedure, post-operative month (POM) 1 BCVA to assess the speed of visual recovery, endothelial cell count (ECC), absolute refractive error, surgical duration, and complication rates. Additional subgroup analyses were performed based on surgeon experience with the technique. Single-surgeon studies had an average of 26 procedures performed, whereas multiple-surgeon studies averaged only 9 procedures performed; these were then used to delineate surgeon experience. A sample-size weighted mean difference (MD) meta-analysis was performed across all variables using RevMan 5.4.1; p < 0.05 was considered statistically significant. Results: Thirteen studies with 737 eyes were included: 406 eyes were included in the SSF group, and 331 eyes were included in the Yamane group. There was no significant difference in the final BCVA between groups in both the single-surgeon versus multiple-surgeon studies (MD = -0.01, 95% CI: [-0.06, 0.04], p = 0.73). In the single-surgeon studies, the BCVA at POM1 was significantly improved in the Yamane group compared to SSF (MD = -0.10, 95% CI: [-0.16, -0.04], p = 0.002). In the multiple-surgeon studies, there was no significant difference in BCVA at POM1 (MD = -0.06, 95% CI: [-0.16, 0.04], p = 0.23). The Yamane group had a shorter surgical duration than SSF in both single-surgeon and multiple-surgeon studies (MD = -24.68, 95% CI: [-35.90, -13.46], p < 0.0001). The ECC, refractive error, and complication rates did not significantly differ amongst all groups. Conclusions: The Yamane technique demonstrated similar long-term visual outcomes and complication rates to the traditional SSF. Visual recovery was significantly faster in the Yamane group in the single-surgeon studies. The operative times were shorter across all Yamane groups. Based on these findings, it is advisable to consider the Yamane technique as a viable, and perhaps preferable, option for patients requiring secondary IOL placement, alongside traditional SSF methods.

180° versus 360° Selective Laser Trabeculoplasty in Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis.

PRECIS: This systematic review and meta-analysis found that 360° selective laser trabeculoplasty (SLT) is significantly more effective than 180° SLT at reducing intraocular pressure at one month and one year follow-ups, without increased serious adverse event risk. PURPOSE: To determine the efficacy of 180° versus 360° selective laser trabeculoplasty (SLT) in adults with open angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: A systematic review was performed using PubMed, Embase, and Scopus databases, from 1995 to December 30, 2023, for studies comparing 180° and 360° SLT in adults with OAG and OHT (PROSPERO ID: CRD42024497832). Meta-analyses were performed to calculate nominal percent and raw reductions in IOP between treatment groups at one-month, one-year, and two-year follow-ups, as well as success rates, defined as a 20% or greater IOP reduction. RESULTS: Nine studies with 1044 eyes were included; 491 received 180°SLT and 553 received 360° SLT. At the one-month follow-up, 360° SLT reduced IOP by 3.45% more (WMD=3.45; 95% CI: 2.02-4.88; P<0.00001) and 0.87 mmHg more (WMD=0.87; 95% CI: 0.35-1.38; P=0.0010). At the one-year follow-up, 360° SLT reduced IOP by 4.33% more (WMD=4.33; 95% CI: 2.35-6.32; P<0.0001) and 1.15 mmHg more (WMD=1.15; 95% CI: 0.25-2.04; P=0.01). At two years of follow up, 360° SLT reduced IOP by 4.86% more (WMD=4.86; 95% CI: -0.32, 10.0; P=0.07) and 1.25 mmHg more (WMD=1.25; 95% CI: -0.29, 2.79; P=0.11), however the difference was not statistically significant. Compared to 360° SLT, 180° SLT had a significantly lower success rate (OR=0.50; 95% CI: 0.35-0.72; P=0.0002). There was no difference in serious complications between interventions. CONCLUSION: 360° SLT is more effective than 180° SLT at lowering IOP at one-month and one-year follow-ups as well as achieving successful IOP control without increased risk of serious complications.

Outcomes of Chandelier-Assisted Scleral Buckling in Rhegmatogenous Retinal Detachments: Systematic Review and Meta-analysis.

Purpose: To examine the outcomes of chandelier endoillumination-assisted scleral buckling (chandelier scleral buckling) for rhegmatogenous retinal detachments (RRDs) and compare them with those of standard scleral buckling using indirect ophthalmoscopy. Methods: A literature search was performed on April 15, 2023. Outcomes analyzed included the primary anatomic success rates, surgical duration, and complication rates. A meta-analysis of proportions estimated the pooled success rate of chandelier scleral buckling. In addition, meta-analyses compared the success rates between pseudophakic eyes and phakic eyes having chandelier scleral buckling and compared success rates and surgical duration between standard scleral buckling and chandelier scleral buckling. Results: Thirty studies with 1133 eyes were included. The pooled primary anatomic success rate of chandelier scleral buckling was 91.7% (95% CI, 89.6%-93.6%). In studies comparing success rates between the 2 techniques, there was no significant difference (risk ratio, 1.01; 95% CI, 0.94-1.08; P = .80). The surgical times were significantly shorter with chandelier scleral buckling than with standard scleral buckling (mean difference, -18.83; 95% CI, -30.88 to -6.79; P = .002). There was no significant difference in the success rate between pseudophakic eyes and phakic eyes (risk ratio, 0.99; 95% CI, 0.91-1.08; P = .89). No cases of endophthalmitis were reported. Conclusions: Chandelier endoillumination-assisted scleral buckling may be a promising technique given its high rate of primary anatomic success for RRDs and success rates similar to those of standard scleral buckling. There was no significant difference in the efficacy of chandelier scleral buckling between pseudophakic eyes and phakic eyes.

Correlations between Steady-State Pattern Electroretinogram and Humphrey Visual Field Analyzer Global Indices and Their Associations with Retinal Ganglion Cell Layer-Inner Plexiform Layer Thickness in Glaucoma Suspects.

Purpose: The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). Materials and Methods: This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Results: Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. Conclusions: ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression.

Stimulant Patterns, Alone or with Other Psychotropic Classes, in Medicaid-Insured Youth Continuously Enrolled for 3-8 Years.

Objective: Little U.S. pharmacoepidemiologic study is based on treatment during continuous enrollment for periods more than a year. This study aims to show pediatric patterns of stimulant use (alone or with other psychotropic classes) from Medicaid administrative claims data for stimulant patterns of 3- to 8-year continuous enrollees. Methods: A retrospective cohort study was derived from Medicaid enrollment, pharmacy, and diagnosis claims data (2007-2014) in a mid-Atlantic state. Youth aged 2-17 years with 3-8 years of continuous enrollment treated with stimulants were compared with a date-matched comparison group treated without stimulants. Major outcomes include prevalence and duration of stimulant use and patterns of stimulant polypharmacy across relatively long enrollments (3-8 years). Results: Among 264,518 unique 2- to 17-year olds with 3-8 years of continuous enrollment, 16.5% had stimulant prescription dispensings, doubling the annual national prevalence of 8.1%. Subgroup analysis showed that the highest prevalence of stimulant use was for 6- to 11-year olds (20.4%), foster care eligible youth (42.3%), and those with 7-8 years of continuous enrollment (20.1%). Externalizing psychiatric disorders were far more common in those treated with stimulants than in those treated without stimulants. The duration of stimulant exposure overall was a median of 487 days, half that of foster care stimulant users. Stimulant polypharmacy with two or more psychotropic classes concomitantly characterized 29.8% of stimulant users. Among those with three or four or more class polypharmacy, 85% and 88%, respectively, had concomitant stimulant and antipsychotic use. The adjusted odds ratio (AOR) of three or more class polypharmacy significantly increased in 12- to 17-year-old age group (AOR = 1.8), foster care eligibility (AOR = 4.5), and among those with the longest enrollment (AOR = 1.7). Conclusions and Relevance: Stimulant prevalence in Medicaid-insured youth with continuous enrollment of 3-8 years was twice as common as in annual data sets. Future research should investigate three to five interclass stimulant polypharmacy effectiveness in reliably diagnosed community populations.

AutoTransOP: translating omics signatures without orthologue requirements using deep learning.

The development of therapeutics and vaccines for human diseases requires a systematic understanding of human biology. Although animal and in vitro culture models can elucidate some disease mechanisms, they typically fail to adequately recapitulate human biology as evidenced by the predominant likelihood of clinical trial failure. To address this problem, we developed AutoTransOP, a neural network autoencoder framework, to map omics profiles from designated species or cellular contexts into a global latent space, from which germane information for different contexts can be identified without the typically imposed requirement of matched orthologues. This approach was found in general to perform at least as well as current alternative methods in identifying animal/culture-specific molecular features predictive of other contexts-most importantly without requiring homology matching. For an especially challenging test case, we successfully applied our framework to a set of inter-species vaccine serology studies, where 1-to-1 mapping between human and non-human primate features does not exist.

Disruption of CFAP418 interaction with lipids causes widespread abnormal membrane-associated cellular processes in retinal degenerations.

Syndromic ciliopathies and retinal degenerations are large heterogeneous groups of genetic diseases. Pathogenic variants in the CFAP418 gene may cause both disorders, and its protein sequence is evolutionarily conserved. However, the disease mechanism underlying CFAP418 mutations has not been explored. Here, we apply quantitative lipidomic, proteomic, and phosphoproteomic profiling and affinity purification coupled with mass spectrometry to address the molecular function of CFAP418 in the retina. We show that CFAP418 protein binds to the lipid metabolism precursor phosphatidic acid (PA) and mitochondrion-specific lipid cardiolipin but does not form a tight and static complex with proteins. Loss of Cfap418 in mice disturbs membrane lipid homeostasis and membrane-protein associations, which subsequently causes mitochondrial defects and membrane-remodeling abnormalities across multiple vesicular trafficking pathways in photoreceptors, especially the endosomal sorting complexes required for transport (ESCRT) pathway. Ablation of Cfap418 also increases the activity of PA-binding protein kinase Cα in the retina. Overall, our results indicate that membrane lipid imbalance is a pathological mechanism underlying syndromic ciliopathies and retinal degenerations which is associated with other known causative genes of these diseases.

Family-wide analysis of integrin structures predicted by AlphaFold2.

Recent advances in protein structure prediction using AlphaFold2, known for its high efficiency and accuracy, have opened new avenues for comprehensive analysis of all structures within a single protein family. In this study, we evaluated the capabilities of AphaFold2 in analyzing integrin structures. Integrins are heterodimeric cell surface receptors composed of a combination of 18 α and 8 ß subunits, resulting in a family of 24 different members. Both α and ß subunits consist of a large extracellular domain, a short transmembrane domain, and typically, a short cytoplasmic tail. Integrins play a pivotal role in a wide range of cellular functions by recognizing diverse ligands. Despite significant advances in integrin structural studies in recent decades, high-resolution structures have only been determined for a limited subsets of integrin members, thus limiting our understanding of the entire integrin family. Here, we first analyzed the single-chain structures of 18 α and 8 ß integrins in the AlphaFold2 protein structure database. We then employed the newly developed AlphaFold2-multimer program to predict the α/ß heterodimer structures of all 24 human integrins. The predicted structures show a high level of accuracy for the subdomains of both α and ß subunits, offering high-resolution structure insights for all integrin heterodimers. Our comprehensive structural analysis of the entire integrin family unveils a potentially diverse range of conformations among the 24 members, providing a valuable structure database for studies related to integrin structure and function. We further discussed the potential applications and limitations of the AlphaFold2-derived integrin structures.

56 Fe ion exposure increases the incidence of lung and brain tumors at a similar rate in male and female mice.

The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly four-fold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development post-HZE radiation exposure, we irradiated Rb fl/fl ; Trp53 fl/+ male and female mice infected with Adeno-Cre with various doses of 320 kVp X-rays or 600 MeV/n 56 Fe ions and monitored them for any radiation-induced malignancies. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in X-ray and 56 Fe ion-exposed mice, respectively. In addition, 1 Gy 56 Fe ion exposure compared to X-rays led to a significantly higher incidence of lung adenomas/carcinomas (p=0.02) and ENBs (p<0.0001). However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in X-ray and 56 Fe ion-induced ENBs. Thus, our data revealed that 56 Fe ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X-rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality.

Adenylyl cyclase 6 plays a minor role in the mouse inner ear and retina.

Adenylyl cyclase 6 (AC6) synthesizes second messenger cAMP in G protein-coupled receptor (GPCR) signaling. In cochlear hair cells, AC6 distribution relies on an adhesion GPCR, ADGRV1, which is associated with Usher syndrome (USH), a condition of combined hearing and vision loss. ADGRV1 is a component of the USH type 2 (USH2) protein complex in hair cells and photoreceptors. However, the role of AC6 in the inner ear and retina has not been explored. Here, we found that AC6 distribution in hair cells depends on the USH2 protein complex integrity. Several known AC6 regulators and effectors, which were previously reported to participate in ADGRV1 signaling in vitro, are localized to the stereociliary compartments that overlap with AC6 distribution in hair cells. In young AC6 knockout (Adcy6-/-) mice, the activity of cAMP-dependent protein kinase, but not Akt kinase, is altered in cochleas, while both kinases are normal in vestibular organs. Adult Adcy6-/- mice however exhibit normal hearing function. AC6 is expressed in mouse retinas but rarely in photoreceptors. Adcy6-/- mice have slightly enhanced photopic but normal scotopic vision. Therefore, AC6 may participate in the ADGRV1 signaling in hair cells but AC6 is not essential for cochlear and retinal development and maintenance.

Family-wide analysis of integrin structures predicted by AlphaFold2.

Recent advances in protein structure prediction using AlphaFold2, known for its high efficiency and accuracy, have opened new avenues for comprehensive analysis of all structures within a single protein family. In this study, we evaluated the capabilities of AphaFold2 in analyzing integrin structures. Integrins are heterodimeric cell surface receptors composed of a combination of 18 α and 8 ß subunits, resulting in a family of 24 different members. Both α and ß subunits consist of a large extracellular domain, a short transmembrane domain, and typically, a short cytoplasmic tail. Integrins play a pivotal role in a wide range of cellular functions by recognizing diverse ligands. Despite significant advances in integrin structural studies in recent decades, high-resolution structures have only been determined for a limited subsets of integrin members, thus limiting our understanding of the entire integrin family. Here, we first analyzed the single-chain structures of 18 α and 8 ß integrins in the AlphaFold2 protein structure database. We then employed the newly developed AlphaFold2-multimer program to predict the α/ß heterodimer structures of all 24 human integrins. The predicted structures show a high level of accuracy for the subdomains of both α and ß subunits, offering high-resolution structure insights for all integrin heterodimers. Our comprehensive structural analysis of the entire integrin family unveils a potentially diverse range of conformations among the 24 members, providing a valuable structure database for studies related to integrin structure and function. We further discussed the potential applications and limitations of the AlphaFold2-derived integrin structures.

Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus.

ATRX is one of the most frequently altered genes in solid tumors, and mutation is especially frequent in soft tissue sarcomas. However, the role of ATRX in tumor development and response to cancer therapies remains poorly understood. Here, we developed a primary mouse model of soft tissue sarcoma and showed that Atrx-deleted tumors were more sensitive to radiation therapy and to oncolytic herpesvirus. In the absence of Atrx, irradiated sarcomas had increased persistent DNA damage, telomere dysfunction, and mitotic catastrophe. Our work also showed that Atrx deletion resulted in downregulation of the CGAS/STING signaling pathway at multiple points in the pathway and was not driven by mutations or transcriptional downregulation of the CGAS/STING pathway components. We found that both human and mouse models of Atrx-deleted sarcoma had a reduced adaptive immune response, markedly impaired CGAS/STING signaling, and increased sensitivity to TVEC, an oncolytic herpesvirus that is currently FDA approved for the treatment of aggressive melanomas. Translation of these results to patients with ATRX-mutant cancers could enable genomically guided cancer therapy approaches to improve patient outcomes.

Amniotic Membrane Patching to Assist Closure of Recalcitrant Macular Holes.

BACKGROUND AND OBJECTIVE: This study reports a case series of patients with persistent macular holes (MHs) who underwent human amniotic membrane subretinal placement to achieve successful anatomic MH closure. PATIENTS AND METHODS: This was a retrospective case series of patients with persistently open full-thickness MHs who underwent human amniotic membrane placement. Patients were observed up to 6 months postoperatively. RESULTS: Ten patients were included. The mean preoperative best-corrected visual acuity was 1.6 logMAR (20/800). Postoperatively, mean best-corrected visual acuity improved to 1.3 logMAR (20/400) at 1 month and 1.1 logMAR (20/250) by the 3- and 6-month visits. In all cases, the MH appeared closed at the 1-week visit and remained closed at their last follow-up. Optical coherence tomography showed closure in all cases. No adverse events were reported. CONCLUSIONS: Human amniotic membrane sub-retinal placement may serve as a useful surgical technique to assist in the closure of recalcitrant macular holes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:218-222.].

Randomized Prospective Evaluation of Microblepharoexfoliation BlephEx as Adjunctive Therapy in the Treatment of Chalazia.

PURPOSE: Chalazia are benign eyelid lesions caused by the obstruction and inflammatory reaction of the meibomian glands. Demodex mites are one potential cause of chalazia leading to mechanical obstruction of the meibomian gland. In this prospective randomized study, we examine a novel approach to treating chalazia with the use of microblepharoexfoliation (MBE), an in-office lid hygiene technique that exfoliates the eyelid margins. METHODS: Fifty patients with clinical evidence of acute chalazion were enrolled in this study. Subjects were randomly assigned to a MBE plus lid hygiene group (23 patients, mean age 66.6 ± 16.6 years) or a lid hygiene alone group (27 patients, mean age 62.1 ± 14.4). The MBE plus lid hygiene group received MBE treatment and were evaluated 1 month after the baseline visit. The main outcome measured was the resolution of the chalazion at the 1-month follow-up visit. RESULTS: The lid hygiene plus MBE treatment group demonstrated a statistically significant resolution of the chalazion compared with the lid hygiene group alone ( P = 0.007; chi-square test). Among the MBE plus hygiene group, 87% of the patients had resolution of their chalazion as opposed to the lid hygiene alone group, which had 44% resolution. CONCLUSIONS: This is the first prospective, randomized clinical trial that demonstrated efficacy of MBE as a noninvasive adjunctive treatment method for chalazion resolution.

Exogenous cryptococcal endophthalmitis in an immunocompetent patient.

We describe a case of exogenous cryptococcal endophthalmitis without central nervous system (CNS) involvement or systemic infection in an immunocompetent patient. An 82-year-old male with hypertension, hyperlipidemia, type 2 diabetes mellitus, and primary open-angle glaucoma with a history of left eye trabeculectomy presented with 3 months of worsening left eye pain and redness. Vitreous cultures resulted as Cryptococcus, prompting treatment with intravitreal amphotericin and further investigation. Systemic workup was unrevealing for an endogenous source, CNS involvement, or immunocompromising conditions. He was treated with an aggressive regimen of systemic antifungals, leading to subjective improvements in clinical exam and in vision.

Topical Dexamethasone as an Adjuvant to Mineralocorticoid Receptor Antagonists for the Treatment of Recalcitrant Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: A previous report demonstrated efficacy of mineralocorticoid antagonist with adjuvant topical dexamethasone (MRA+DEX) in resolving subretinal fluid (SRF) in a chronic central serous chorioretinopathy (CSCR) patient. This pilot study investigates the use of MRA+DEX to treat recalcitrant, chronic CSCR patients. STUDY DESIGN: Retrospective review of chronic, recalcitrant CSCR patients unresponsive to MRA alone who were treated with MRA+DEX and followed for up to 3 months. Apical SRF thickness and visual acuity were measured. RESULTS: Ten eyes of eight chronic, recalcitrant patients were included with an average follow-up of 109 days. Mean percent reduction in apical fluid thickness at one month and at last follow-up after adding dexamethasone (DEX) was 33% and 52%, respectively. Five eyes (50%) achieved complete resolution of SRF. Three eyes (30%) showed partial response and two (20%) eyes had no response. There was no significant change in visual acuity. CONCLUSIONS: MRA+DEX decreased SRF in some recalcitrant, chronic CSCR patients. Large prospective studies are needed to evaluate the utility of MRA+DEX in these chronic CSCR patients. [Ophthalmic Surg Lasers Imaging Retina 2022;53:659-665.].

Toll-like receptor agonists, poly(I:C) and flagellin, lead to IL-36γ induction with divergent release kinetics and differentially alter autophagy in primary human keratinocytes

IL-36γ, a pro-inflammatory member of the IL-1 cytokine superfamily, can be induced and secreted by normal human foreskin keratinocytes (HFKs) in response to pathogenic stimuli, however, the mechanisms underlying the secretion are unknown. In this study, we demonstrate that stimulation with the TLR3 agonist, poly (I:C), led to a delayed secretion of IL-36γ compared to stimulation with the TLR5 agonist, flagellin, despite equal levels of the cytokine (p = 0.006). IL-36γ was shown to be released from HFKs in its inactive, uncleaved form, based on western blotting. Moreover, recombinant IL-36γ in its activated, cleaved form induced endogenous IL-36γ 10-fold (p = 0.004) and CXCL8 five-fold (p = 0.003) over baseline levels compared to unactivated full-length recombinant IL-36γ. The ratio of LC3b-II/LC3b-I was significantly higher in poly(I:C)-treated cells compared to flagellin-treated and unstimulated controls without a change in SQSTM1/p62 after 24 hours of stimulation (p = 0.043). Under fluorescence microscopy, poly(I:C) led to a two-fold increase at eight hours and four-fold increase at 24 hours in accumulated autophagosomes post-stimulation (p = 0.032). In contrast, autophagosomes were unchanged relative to baseline in response to flagellin. Bafilomycin A1 treatment enhanced poly(I:C)-mediated IL-36γ secretion (p = 0.044) while rapamycin led to a noticeable, but non-significant, increase in flagellin-mediated IL-36γ secretion, indicating that interrupting autophagic flux can alter IL-3γ grelease from HFKs. Finally, we show that, compared to clinically normal laryngeal tissue, there were significantly higher levels of LC3b-II in HPV-infected respiratory papilloma tissue, indicating a higher number of autophagosomes; a signature of disrupted autophagic flux.

Neuro-ophthalmology malpractice: A review of the Westlaw Database.

BACKGROUND: Neuro-ophthalmologic conditions are at a higher risk of misdiagnosis compared to other ophthalmic conditions. Increased awareness of the most common diagnostic errors in neuro-ophthalmology that lead to malpractice claims can allow ophthalmologists to further improve their diagnostic workup to reduce delays in diagnosis and management, while also mitigating the risk of litigation. METHODS: Malpractice trials in the Westlaw Legal Database that involved cases of neuro-ophthalmologic diagnostic errors or failures by ophthalmologists were included in this study. RESULTS: A total of 43 cases were included, all citing failure to diagnose as the main reason for litigation. The most common diagnoses missed were cerebrovascular pathologies (30.2%), intracranial tumours (27.9%) and giant cell arteritis (25.6%). The majority of verdicts were in favour of the defendants (48.8%). After adjusting for inflation, the average amount awarded was $1,952,154. CONCLUSION: Nearly half of the cases resulted in a defendant verdict. Settlement and plaintiff verdicts were costly, with average awards of approximately two million inflation-adjusted dollars. Failure to diagnose cerebrovascular pathologies was the most common diagnostic error followed by failure to diagnose intracranial tumours and giant cell arteritis. It is crucial for ophthalmologists to be aware of the most common pitfalls that lead to misdiagnosis or delays in diagnosis of neuro-ophthalmologic conditions.

Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects.

Aim: To investigate whether steady state pattern electroretinogram (ssPERG) could identify retinal ganglion cell (RGC) dysfunction, and to assess the relationship between ssPERG with optical coherence tomography (OCT) measurements in glaucoma suspects (GS). Materials and methods: This was a prospective cohort study of GS, identified based on suspicious optic disk appearance and glaucoma risk factors. Complete eye exam, Standard automated perimetry, OCT, and ssPERG were performed. Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio were subsequently used in the correlation and linear regression analyses between ssPERG parameters and the RNFL, GCL/IPL, and macular thicknesses measurements. Results: Forty-nine eyes of 26 patients were included. Mag and MagD were significantly correlated with the superior, inferior, and average RNFL thicknesses (avRNFLT). All ssPERG parameters were significantly correlated with the average and minimum GCL/IPL thicknesses and the inner macular sector thicknesses. Mag and MagD significantly predicted the superior, inferior, and avRNFLT in the regression analysis. All ssPERG parameters were predictive of GCL/IPL thickness in all sectors as well as the average and minimum GCL/IPL thicknesses. All ssPERG parameters were predictive of all inner macular sector thicknesses and MagD was also predictive of some outer macular sector thicknesses as well. Conclusion: ssPERG has significant correlations with and is predictive of RNFL, GCL/IPL, and macular thicknesses in glaucoma suspects. Clinical significance: ssPERG may serve as a useful objective functional tool for identifying and following the progression of disease in glaucoma suspects. How to cite this article: Tirsi A, Wong A, Zhu D, et al. Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects. J Curr Glaucoma Pract 2022;16(2):96-104.

Defining the determinants of protection against SARS-CoV-2 infection and viral control in a dose-down Ad26.CoV2.S vaccine study in nonhuman primates.

Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.