Nuclear speckle rejuvenation alleviates proteinopathies at the expense of YAP1.

Current treatments targeting individual protein quality control have limited efficacy in alleviating proteinopathies, highlighting the prerequisite for a common upstream druggable target capable of global proteostasis modulation. Building on our prior research establishing nuclear speckles as pivotal organelles responsible for global proteostasis transcriptional control, we aim to alleviate proteinopathies through nuclear speckle rejuvenation. We identified pyrvinium pamoate as a small-molecule nuclear speckle rejuvenator that enhances protein quality control while suppressing YAP1 signaling via decreasing the surface tension of nuclear speckle condensates through interaction with the intrinsically disordered region of nuclear speckle scaffold protein SON. In pre-clinical models, pyrvinium pamoate reduced tauopathy and alleviated retina degeneration by promoting autophagy and ubiquitin-proteasome system. Aberrant nuclear speckle morphology, reduced protein quality control and increased YAP1 activity were also observed in human tauopathies. Our study uncovers novel therapeutic targets for tackling protein misfolding disorders within an expanded proteostasis framework encompassing nuclear speckles and YAP1.

Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery: A Pilot Study.

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intrastromal Corneal Ring Segment Implantation Followed by Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Cross-Linking for Contact Lens-Intolerant Keratoconus.

PURPOSE: This study aimed to evaluate the efficacy and safety of Keraring implantation followed by simultaneous topography-guided photorefractive keratectomy (TGPRK) and corneal cross-linking (CXL) in the management of keratoconus. METHODS: This is a single-center, private practice, retrospective review. Patients with keratoconus who were intolerant to contact lens wear underwent implantation of the Keraring, followed by TGPRK with CXL from 2 to 36 months after implantation. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction (cylinder and spherical equivalent), keratometry (steep, maximum, and central), and central corneal thickness (CCT). Patients were followed up for 3 to 60 months postoperatively. RESULTS: Fifty-seven eyes from 45 patients were included. The mean time between Keraring and TGPRK/CXL was 6.0 ± 6.0 months. Patients were followed up for a mean of 28.6 ± 20.1 months after Keraring insertion. At 12-month follow-up, there was a statistically significant improvement in mean UDVA (0.94 ± 0.49-0.35 ± 0.23, P < 0.01), CDVA (0.39 ± 0.26-0.17 ± 0.15, P < 0.01), cylinder (-4.97 ± 2.68 to -1.74 ± 1.25, P < 0.01), steep keratometry (51.25 ± 3.37-45.03 ± 2.27, P < 0.01), central keratometry (52.59 ± 4.98-46.99 ± 3.53, P < 0.01), and maximum keratometry (58.78 ± 4.22-50.76 ± 3.42, P < 0.01). These results were sustained at 48-month follow-up. CCT decreased at 12 months after TGPRK (461.84 ± 27.46-418.94 ± 45.62, P < 0.01) and remained stable at 60 months. Postoperatively, 2 eyes (3.51%) had corneal haze, resulting in decrease in CDVA; 1 was treated successfully with repeat PRK; and 1 patient (1.75%) had wound melt due to partial Keraring extrusion, which settled with repositioning. CONCLUSIONS: Keraring implantation followed by simultaneous TGPRK and CXL appears to be effective in the long term in improving UDVA, CDVA, cylinder, CCT, and keratometry in patients with keratoconus who are intolerant to contact lenses.

Impact of Type 2 diabetes mellitus and insulin use on progression to glaucoma surgery in primary open angle glaucoma.

PURPOSE: To investigate outcomes of primary open-angle glaucoma (POAG) patients with and without type 2 diabetes mellitus (T2DM). METHODS: Retrospective observational study using U.S. nationwide healthcare insurance claims database. Patients ≥40 years old with at least one HbA1c within one year of POAG diagnosis were included. Diabetic factors associated with POAG progression requiring glaucoma surgery were evaluated using multivariable Cox proportional hazards regression models adjusted for demographic, diabetic and glaucoma factors. T2DM diagnosis and use of either oral hypoglycaemic agents or insulin therapy were assessed in association with POAG progression requiring glaucoma surgery. RESULTS: 104,515 POAG patients were included, of which 70,315 (67%) had T2DM. The mean age was 68.9 years (Standard deviation 9.2) and 55% were female. Of those with T2DM, 93% were taking medication (65,468); 95% (62,412) taking oral hypoglycaemic agents, and 34% (22,028) were on insulin. In multivariable analyses, patients with T2DM had a higher hazard of requiring glaucoma surgery (Hazard ratio, HR 1.15, 95% CI 1.09-1.21, p < 0.001). Higher mean HbA1c was also a significant predictor of progression requiring glaucoma surgery (HR 1.02, 95% CI 1.01-1.03, p < 0.001). When evaluating only patients who were taking antidiabetic medication, after adjusting for confounders, insulin use was associated with a 1.20 higher hazard of requiring glaucoma surgery compared to oral hypoglycaemic agents (95% CI 1.14-1.27, p < 0.001), but when stratified by HbA1c, this effect was only significant for those with HbA1c > 7.5%. CONCLUSIONS: Higher baseline HbA1c, particularly in patients taking insulin may be associated with higher rates of glaucoma surgery in POAG.

A case study in applying artificial intelligence-based named entity recognition to develop an automated ophthalmic disease registry.

PURPOSE: Advances in artificial intelligence (AI)-based named entity extraction (NER) have improved the ability to extract diagnostic entities from unstructured, narrative, free-text data in electronic health records. However, there is a lack of ready-to-use tools and workflows to encourage the use among clinicians who often lack experience and training in AI. We sought to demonstrate a case study for developing an automated registry of ophthalmic diseases accompanied by a ready-to-use low-code tool for clinicians. METHODS: We extracted deidentified electronic clinical records from a single centre's adult outpatient ophthalmology clinic from November 2019 to May 2022. We used a low-code annotation software tool (Prodigy) to annotate diagnoses and train a bespoke spaCy NER model to extract diagnoses and create an ophthalmic disease registry. RESULTS: A total of 123,194 diagnostic entities were extracted from 33,455 clinical records. After decapitalisation and removal of non-alphanumeric characters, there were 5070 distinct extracted diagnostic entities. The NER model achieved a precision of 0.8157, recall of 0.8099, and F score of 0.8128. CONCLUSION: We presented a case study using low-code artificial intelligence-based NLP tools to produce an automated ophthalmic disease registry. The workflow created a NER model with a moderate overall ability to extract diagnoses from free-text electronic clinical records. We have produced a ready-to-use tool for clinicians to implement this low-code workflow in their institutions and encourage the uptake of artificial intelligence methods for case finding in electronic health records.

Detection of systemic cardiovascular illnesses and cardiometabolic risk factors with machine learning and optical coherence tomography angiography: a pilot study.

BACKGROUND/OBJECTIVES: Optical coherence tomography angiography (OCTA) has been found to identify changes in the retinal microvasculature of people with various cardiometabolic factors. Machine learning has previously been applied within ophthalmic imaging but has not yet been applied to these risk factors. The study aims to assess the feasibility of predicting the presence or absence of cardiovascular conditions and their associated risk factors using machine learning and OCTA. METHODS: Cross-sectional study. Demographic and co-morbidity data was collected for each participant undergoing 3 × 3 mm, 6 × 6 mm and 8 × 8 mm OCTA scanning using the Carl Zeiss CIRRUS HD-OCT model 5000. The data was then pre-processed and randomly split into training and testing datasets (75%/25% split) before being applied to two models (Convolutional Neural Network and MoblieNetV2). Once developed on the training dataset, their performance was assessed on the unseen test dataset. RESULTS: Two hundred forty-seven participants were included. Both models performed best in predicting the presence of hyperlipidaemia in 3 × 3 mm scans with an AUC of 0.74 and 0.81, and accuracy of 0.79 for CNN and MobileNetV2 respectively. Modest performance was achieved in the identification of diabetes mellitus, hypertension and congestive heart failure in 3 × 3 mm scans (all with AUC and accuracy >0.5). There was no significant recognition for 6 × 6 and 8 × 8 mm for any cardiometabolic risk factor. CONCLUSION: This study demonstrates the strength of ML to identify the presence cardiometabolic factors, in particular hyperlipidaemia, in high-resolution 3 × 3 mm OCTA scans. Early detection of risk factors prior to a clinically significant event, will assist in preventing adverse outcomes for people.

Evidence for conservation of primordial ~12-hour ultradian gene programs in humans under free-living conditions.

While circadian rhythms are entrained to the once daily light-dark cycle of the sun, many marine organisms exhibit ~12h ultradian rhythms corresponding to the twice daily movement of the tides. Although human ancestors emerged from circatidal environment millions of years ago, direct evidence of ~12h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells and identified robust ~12h transcriptional rhythms from three healthy participants. Pathway analysis implicated ~12h rhythms in RNA and protein metabolism, with strong homology to the circatidal gene programs previously identified in Cnidarian marine species. We further observed ~12h rhythms of intron retention events of genes involved in MHC class I antigen presentation, synchronized to expression of mRNA splicing genes in all three participants. Gene regulatory network inference revealed XBP1, and GABP and KLF transcription factor family members as potential transcriptional regulators of human ~12h rhythms. These results suggest that human ~12h biological rhythms have a primordial evolutionary origin with important implications for human health and disease.

Glaucoma and Myopia: Diagnostic Challenges.

The rising global prevalence of myopia is a growing concern for clinicians, as it predisposes patients to severe ocular pathologies including glaucoma. High myopia can be associated with clinical features that resemble glaucomatous damage, which make an accurate glaucoma diagnosis challenging, particularly among patients with normal intraocular pressures. These patients may also present with established visual field defects which can mimic glaucoma, and standard imaging technology is less useful in disease detection and monitoring due to the lack of normative data for these anatomically unique eyes. Progression over time remains the most critical factor in facilitating the detection of early glaucomatous changes, and thus careful longitudinal follow-up of high-risk myopic patients is the most important aspect of management. Here, we review our current understanding of the complex relationship between myopia and glaucoma, and the diagnostic challenges and limitations of current testing protocols including visual field, intraocular pressure, and imaging. Furthermore, we discuss the clinical findings of two highly myopic patients with suspected glaucoma.

Establishing human lacrimal gland cultures from biopsy-sized tissue specimens.

OBJECTIVES: To establish cultures of human lacrimal gland from patient-derived, biopsy-sized, tissue specimens. METHODS: Tissue was obtained after surgical removal from patients without dry eye disease undergoing routine procedures. Samples were subjected to mechanical and enzymatic digestion and resulting cell suspensions were plated onto collagen-coated glass coverslips and grown for up to 21 days. Cultures were analysed by immunocytochemistry and light microscopy, and resultant cellular distributions were compared to those in sections of fixed human lacrimal gland tissue. RESULTS: Dissociation of biopsy-sized pieces of human lacrimal gland and seeding onto coated surfaces allowed development of a mixed population of cells in vitro. Within 7-14 days, cellular aggregation was observed and by 21 days many cells had organised themselves into distinct three-dimensional complexes. Immunohistochemistry revealed a heterogeneous population of cells, including epithelial, myoepithelial, mesenchymal and progenitor cells. Some of the epithelia labelled positively for lysozyme and lactoferrin. CONCLUSIONS: Collection and dissociation of biopsy-sized pieces of human lacrimal gland leads to a cellular preparation that can proliferate in vitro and organise into three-dimensional structures. This is the first report detailing that biopsy-collected specimens of human lacrimal gland can be used to establish cell cultures.

Changes in glaucoma management following visual field testing and optical coherence tomography.

BACKGROUND: Optimal utilisation of investigations in glaucoma management remains unclear. We aimed to assess whether a temporal association exists between such testing and management changes. METHODS: Retrospective observational study using nationwide healthcare insurance claims database. Glaucoma outpatient encounters from patients aged ≥40 years with/without Humphrey visual field (HVF) and/or optical coherence tomography (OCT) were identified. An encounter was considered associated with an intervention if surgery occurred within 90 days, or if medication change or laser trabeculoplasty (LT) occurred within 30 days. RESULTS: 12 669 324 outpatient encounters of 1 863 748 individuals from 2003 to 2020 were included. HVF and OCT was performed during 32.8% and 22.2% of encounters respectively. Of the 36 763 (0.3%) encounters preceding surgery, 28.1% included HVF, 11.9% had OCT and 8.5% both. 79 181 (0.6%) visits preceded LT, of which 28.2% had HVF, 13.2% OCT and 9.3% both. Of the 515 899 (4.5%) encounters preceding medication changes, 29.1% had HVF, 16.7% OCT and 12.2% both. Compared with encounters with no investigations, those with HVF and/or OCT were associated with a 49% increased odds of a management change (p<0.001). In multivariate analyses, compared with encounters without investigations, visits with HVF alone had higher odds of subsequent surgery and LT, while HVF and/or OCT were associated with higher odds of medication change (p<0.001 for all). CONCLUSION: Glaucoma therapeutic changes occurred following approximately 5% of outpatient encounters. Surgery and LT were more likely to occur following a visit with a HVF rather than an OCT, while either investigation was associated with a higher odds of medication change.

Nationwide Trends in Vitreoretinal Procedures within Australia.

PURPOSE: To investigate Australian age stratified nationwide trends in vitreoretinal procedures. METHODS: Nationwide retrospective analysis of vitreoretinal procedures in Australia over 2001-2019 using Australian National Hospital Morbidity Database for public and private hospitals. Age and gender-specific trends in selected procedures including pars plana vitrectomy for retinal detachment (PPV for RD), scleral buckle, intravitreal injections, and PPV unrelated to RD were analysed using negative binomial regression. RESULTS: Total included procedures increased from 8102 in 2001 to 136430 in 2019. Between 2001 and 2019, the incidence per 100,000 persons of PPV for RD increased from 7.5 to 20.7, whilst scleral buckling decreased from 10.5 to 4.0. Similarly, the incidence per 100,000 persons of PPV unrelated to RD increased from 18.4 to 67.1, and intravitreal injections increased from 5.6 to 446.0. The rate of scleral buckling decreased by 6% annually (p < .001), most pronounced in those 40 years and above. In contrast, PPV for RD increased by 5% annually (p < .001), also most pronounced in those aged 40 and above. PPV unrelated to RD increased by 7% annually (p < .001), and intravitreal injections increased by 21.0% annually (p < .001). CONCLUSION: Between 2001 and 2019, the rate of scleral buckling declined compared to an increase in PPV for RD. Our analysis suggests an increasing trend to PPV over scleral buckling for RD repair in Australia over the last two decades. Additionally, rates of PPV unrelated to RD and intravitreal injections increased across all age groups. Overall, these trends mirror those seen internationally and reflect changing practice patterns over time.

Blood Pressure Measures and Incident Primary Open-Angle Glaucoma.

Purpose: To investigate the association of systemic blood pressure and incident primary open-angle glaucoma (POAG) using a large open-access database. Methods: Prospective cohort study included 484,268 participants from the UK Biobank without glaucoma at enrollment. Incident POAG events were recorded through assessment visits, hospital inpatient admissions, and primary care data. Blood pressure measures included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). Repeated measurements throughout the study period were analyzed as time-varying covariables. The parameters were modeled as both categorical and continuous nonlinear variables. The primary outcome measure was the relative hazard of incident POAG. Results: There were 2390 incident POAG events over 5,715,480 person-years of follow-up. Median follow-up was 12.08 years. In multivariable analyses, compared to SBP and PP in the normal range (SBP, 120-130 mmHg; PP, 40-50 mmHg), higher SBP and PP were associated with an increased risk of incident POAG (linear trend P = 0.038 for SBP, P < 0.001 for PP). Specifically, SBP of 130 to 140 mmHg or 140 to 150 mmHg was associated with a 1.16 higher hazard of incident POAG (95% CI, 1.01-1.32 and 1.01-1.33, respectively), whereas a PP of greater than 70 mmHg was associated with a 1.13 higher hazard of incident glaucoma (95% CI, 1.00-1.29). In multivariable models, no statistically significant associations were found for DBP or MAP with incident glaucoma. These findings were similar when blood pressure measures were modeled as continuous variables. Conclusions: Higher SBP and PP were associated with an increased risk of incident POAG. Further studies are required to characterize these relationships better.

Histochemical Comparison of Human and Rat Lacrimal Glands: Implications for Bio-Engineering Studies.

Purpose: The purpose of this study was to determine whether rodent lacrimal glands (LGs) represent a suitable surrogate for human tissue in bio-engineering research, we undertook a meticulous histological and histochemical comparison of these two tissues. Methods: Histological techniques and immunohistochemistry were used to compare the structure of adult human and rat LG tissues and the expression of key functional tissue elements. Results: Compared with humans, the rat LG is comprised of much more densely packed acini which are devoid of an obvious central lumen. Myoepithelial, fibroblasts, dendritic cells, T cells, and putative progenitor cells are present in both tissues. However, human LG is replete with epithelium expressing cytokeratins 8 and 18, whereas rat LG epithelium does not express cytokeratin 8. Furthermore, human LG expresses aquaporins (AQPs) 1, 3, and 5, whereas rat LG expresses AQPs 1, 4, and 5. Additionally, mast cells were identified in the rat but not the human LGs and large numbers of plasma cells were detected in the human LGs but only limited numbers were present in the rat LGs. Conclusions: The cellular composition of the human and rat LGs is similar, although there is a marked difference in the actual histo-architectural arrangement of the tissue. Further variances in the epithelial cytokeratin profile, in tissue expression of AQPs and in mast cell and plasma cell infiltration, may prove significant. Translational Relevance: The rat LG can serve as a useful surrogate for the human equivalent, but there exist specific tissue differences meaning that caution must be observed when translating results to patients.

Real-World Outcomes of Glaucoma Filtration Surgery Using Electronic Health Records: An Informatics Study.

PRCIS: Utilizing an automated pipeline for data extraction from electronic health records provides real-world information on the success of various glaucoma procedures, with tube shunt implantation associated with increased failure rates compared with trabeculectomy. BACKGROUND: We aimed to evaluate the long-term survival of glaucoma surgeries using an automated pipeline for extraction of outcomes from electronic health records. METHODS: A retrospective observational study from a single academic center. Patients undergoing trabeculectomy, Ex-PRESS shunt, Baerveldt, and Ahmed tube shunt insertion from 2009 to 2018 were identified from electronic health record procedure codes. Patient characteristics were identified from structured and unstructured fields using a previously validated natural language processing pipeline. RESULTS: Five hundred twelve patients underwent 711 glaucoma surgeries: 287 trabeculectomies, 47 Ex-PRESS shunts, 274 Baerveldt and 103 Ahmed tube implantations. The Median follow-up was 359 days. The mean baseline IOP was 24.4 mm Hg (SD 10.9), and 73.1% were on ≥3 medications. Compared with trabeculectomy, tube shunt surgery had a higher risk of failure (Baerveldt: Hazard Ratio (HR) 1.44, 95% CI 1.02 to 2.02; Ahmed: HR 2.01, 95% CI 1.28 to 3.17). Previous glaucoma surgery was associated with increased failure (≥2 previous surgeries: HR 2.74, 95% CI 1.62 to 4.64), as were fewer baseline medications (<3 medications: HR 2.96, 95% CI 2.12 to 4.13) and male sex (HR 1.40, 95% CI 1.03 to 1.90). At 1 year, tube shunt patients had a 2.53 mm Hg ( P =0.002) higher IOP compared with trabeculectomy patients. CONCLUSIONS: Baerveldt and Ahmed tube shunt implantation was associated with increased failure compared with trabeculectomy. Fewer baseline medications, previous glaucoma surgeries, and male sex were also risk factors for failure. These results demonstrate the utility of applying an informatics pipeline to electronic health records to investigate key clinical questions using real-world evidence.

Automated Identification of Clinical Procedures in Free-Text Electronic Clinical Records with a Low-Code Named Entity Recognition Workflow.

BACKGROUND: Clinical procedures are often performed in outpatient clinics without prior scheduling at the administrative level, and documentation of the procedure often occurs solely in free-text clinical electronic notes. Natural language processing (NLP), particularly named entity recognition (NER), may provide a solution to extracting procedure data from free-text electronic notes. METHODS: Free-text notes from outpatient ophthalmology visits were collected from the electronic clinical records at a single institution over 3 months. The Prodigy low-code annotation tool was used to create an annotation dataset and train a custom NER model for clinical procedures. Clinical procedures were extracted from the entire set of clinical notes. RESULTS: There were a total of 5,098 clinic notes extracted for the study period; 1,923 clinic notes were used to build the NER model, which included a total of 231 manual annotations. The NER model achieved an F-score of 0.767, a precision of 0.810, and a recall of 0.729. The most common procedures performed included intravitreal injections of therapeutic substances, removal of corneal foreign bodies, and epithelial debridement of corneal ulcers. CONCLUSION: The use of a low-code annotation software tool allows the rapid creation of a custom annotation dataset to train a NER model to identify clinical procedures stored in free-text electronic clinical notes. This enables clinicians to rapidly gather previously unidentified procedural data for quality improvement and auditing purposes. Low-code annotation tools may reduce time and coding barriers to clinician participation in NLP research.

Overcoming the impact of physiologic tremors in ophthalmology.

PURPOSE: Ophthalmic surgery involves the manipulation of micron-level sized structures such as the internal limiting membrane where tactile sensation is practically absent. All humans have physiologic tremors that are of low amplitude and not discernible to the naked eye; they do not adversely affect the majority of the population's daily functioning. However, during microsurgery, such tremors can be problematic. In this review, we focus on the impact of physiological tremors on ophthalmic microsurgery and offer a comparative discussion on the impact of such tremors on other surgical specialties. METHODS: A single investigator used the MEDLINE database (via PubMed) to search for and identify articles for inclusion in this systematic review. Ten key factors were identified as potentially having an impact on tremor amplitude: beta-blockers, muscle fatigue, robotic systems, handheld tools/micromanipulators, armrests/wrist supports, caffeine, diet, sleep deprivation, consuming alcohol, and workouts (exercise). These key terms were then searched using the advanced Boolean search tool and operators (i.e., AND, OR) available on PubMed: (*keyword*) AND (surgeon tremor OR microsurgery tremor OR hand steadiness OR simulator score). RESULTS: Ten studies attempted to quantify the baseline severity of operator physiologic tremor. Approximately 89% of studies accessing the impact of tremors on performance in regards to surgical metrics reported an improvement in performance compared to 57% of studies concluding that tremor elimination was of benefit when considering procedural outcomes. CONCLUSIONS: Robotic technology, new instruments, exoskeletons, technique modifications, and lifestyle factors have all demonstrated the potential to assist in overcoming tremors in ophthalmology.

An elusive case of malignant optic nerve glioma with a suprasellar mass.

A 67-year-old man with multiple comorbidities presented with 3 weeks of orbital pain, proptosis, and no light perception vision in the left eye. Examination was notable for a left orbital apex syndrome with CN III, VI palsies, an optic neuropathy, and central retinal vein occlusion. Magnetic resonance imaging of the orbits was notable for extensive enhancement, enlargement, and T2 hyperintensity of the optic nerve, with perineural sheath enhancement, and chiasmal hyperintensity. Inflammatory workup and lumbar puncture were unremarkable. No improvement was seen after a 3-day course of intravenous solumedrol. Initial optic nerve biopsy revealed necrotic nerve tissue, macrophage infiltration, increased vascularization, and peripheral gliosis. The volume of tissue was inadequate for genomic analysis. The patient was lost to follow-up but returned 5 months later with right-sided vision loss. Repeat neuroimaging showed a new suprasellar mass and progressive expansion and enhancement of both optic nerves. Biopsies of the suprasellar mass and left nerve at this time were consistent with a high-grade glial neoplasm, WHO grade IV. This is a rare case of glioblastoma involving the optic nerves and suprasellar region. In such cases, molecular profiling can improve diagnosis and may provide for targeted treatments in the future.

Structural and Metabolic Imaging After Short-term Use of the Balance Goggles System in Glaucoma Patients: A Pilot Study.

PRCIS: Short-term use of the Balance Goggles System (BGS) in glaucoma patients was not associated with the observable changes in conventional ocular coherence tomography (OCT) imaging, but metabolic imaging using peripapillary flavoprotein fluorescence (FPF) may represent a useful adjuctive investigation. OBJECTIVE: To determine whether the intraocular pressure (IOP)-lowering effects of the BGS are accompanied by changes in retinal thickness measured by OCT, retinal vascular density measured by ocular coherence tomography-angiography (OCTA), or novel peripapillary metabolic profiling using FPF measured by a fundus camera. DESIGN: Prospective comparative case-series. SUBJECTS: Eight eyes from 8 patients with open angle glaucoma ranging from mild to severe. METHODS: In this prospective, single-center, open-label, nonrandomized, and single-arm study patients received a baseline evaluation including retinal imaging, then 1 hour of negative pressure application through the BGS, followed by repeat retinal imaging. Participants then used the BGS at home for 1 month and underwent a repeat evaluation at the conclusion of the trial. MAIN OUTCOME MEASURES: Changes in nerve fiber layer thickness, OCTA vascular parameters, and FPF scores. RESULTS: Mean baseline IOP was 18.0±3.1 mmHg and there was no significant change in IOP at follow-up. At 1 month compared with baseline, there was a statistically significant improvement in FPF optic nerve head rim scores (12.7±11.6 to 10.5±7.5; P =0.04). In addition, there was a trend toward an increase in retinal nerve fiber layer thickness after 1 month (69.5±14.2 to 72.0±13.7; P =0.1), but there were no statistically significant differences observable with any of the OCTA vascular parameters either at 1 hour or after 1 month. CONCLUSIONS: There were no significant changes observable using conventional OCT imaging after short-term use of the BGS, although metabolic imaging using FPF may be a useful potential biomarker to complement existing investigations. Additional studies are warranted to further investigate these changes.

RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome.

Purpose: Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research. Methods: Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets. Results: Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated. Conclusions: This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.