Characteristics of ocular hypertension and uveitic glaucoma among patients with noninfectious uveitis.

OBJECTIVE: Ocular hypertension and uveitic glaucoma are important downstream sequela of noninfectious uveitis (NIU). Herein, we describe the clinical outcomes of NIU cases with ocular hypertension and uveitic glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: All adults (≥18 years) with NIU under the care of uveitis subspecialty tertiary care clinics between 2010 and 2021 were included. METHODS: The primary outcomes were baseline and final visual acuity. RESULTS: A total of 216 patients out of 914 (23.6%) cases with NIU had ocular hypertension or uveitic glaucoma over the study period. Of all patients with ocular hypertension or uveitic glaucoma, 46% were corticosteroid responders. Baseline and last median visual acuities were better for the ocular hypertension patients compared with patients with uveitic glaucoma (p < 0.001). A higher proportion of patients with uveitic glaucoma than patients with ocular hypertension required glaucoma surgery (p < 0.001). The regression analyses suggested that baseline visual acuity and anatomical classification are significant predictors of last visual acuity, whereas diagnosis of ocular hypertension versus uveitic glaucoma were significant predictors of requirement for glaucoma surgery (p < 0.001). CONCLUSION: A quarter of patients with NIU in this study developed ocular hypertension or uveitic glaucoma. Approximately half of the patients with ocular hypertension or uveitic glaucoma were deemed to be corticosteroid responders. Baseline and last visual acuity outcomes are better amongst ocular hypertension patients compared with those with uveitic glaucoma. Poor baseline visual acuity and panuveitis are predictors of worse vision at last follow-up. Additionally, diagnosis of uveitic glaucoma was a significant predictor of requirement for glaucoma surgery.

Effectiveness of simulation models and digital alternatives in training ophthalmoscopy: A systematic review.

PURPOSE: Traditional direct ophthalmoscopy (TDO) is the oldest method of fundus examination; however, it has fallen out of use due to its technical difficulty and limitations to clinical utility, amidst the advent of potentially better options. A spectrum of new technologies may help in addressing the shortcomings of TDO: simulation mannequins with non-tracked TDO, simulation models with tracked TDO, and smartphone ophthalmoscopy (SFO). METHODOLOGY: A systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating usage of simulation mannequins/models and SFO in ophthalmology education was performed, from inception till April 2023 with no language restriction. We ensured that we included all possible relevant articles by performing backward reference searching of included articles and published review articles. RESULTS: We reviewed studies on non-tracked TDO (n = 5), tracked TDO (n = 3) and SFO (n = 12). Non-tracked TDO and SFO were superior in training competency relative to control (TDO on real eyes). Intriguingly, tracked TDO was non superior to controls. SFO appears to enhance the learning effectiveness of ophthalmoscopy, due to real-time projection of the retina view, permitting instantaneous and targeted feedback. Learners reported improved ergonomics, including a wider field of view and more comfortable viewing distance. Retention of images and recordings permitted the audit of learning and paves the way for storage of such images in patients' electronic medical record and rapid dissemination for specialist referral. CONCLUSIONS: Smartphone ophthalmoscopy (SFO) permits integration of both the practice and learning of ophthalmoscopy, and the auditing of both. These advantages over traditional methods (with simulation or otherwise) may lead to a paradigm shift in undergraduate ophthalmology education. However, the nascency of SFO necessitates preservation of traditional techniques to tide through this period of transition.

Clinical characteristics of non-infectious uveitis treated with and without systemic immunomodulatory therapy.

OBJECTIVE: To compare the patient characteristics and long-term outcomes for those treated with and without systemic immunomodulatory therapy (IMT) for non-infectious uveitis (NIU). DESIGN: Retrospective cohort study. PARTICIPANTS: All consecutive adults with NIU receiving care at 5 uveitis subspecialty tertiary care clinics between 2010 and 2021. METHODS: Clinical outcomes were evaluated on initial presentation and at the last available follow-up. The main outcome measures were baseline characteristics and final visual acuity. RESULTS: A total of 914 NIU patients (418 IMT, 496 non-IMT) with a median age of 51.0 years and 57.4% female were identified. Over half the patients had bilateral disease, with a significantly higher proportion of bilateral cases in the IMT group compared with the non-IMT group (p < 0.001). The IMT group was more likely to have chronic uveitis (p < 0.001), with a higher proportion of patients experiencing cataracts and cystoid macular edema (p < 0.001 for both). A significantly higher proportion of non-IMT patients had anterior uveitis and an idiopathic etiology (p < 0.001). Overall, visual acuity improved significantly from baseline to last follow-up in the entire cohort (p < 0.001), with a slightly better improvement in the IMT group. Multivariable linear regression analysis suggested that baseline visual acuity and panuveitis were significant predictors of final visual acuity (p < 0.001 for both). CONCLUSIONS: NIU patients on IMT are often younger, suffer from bilateral and chronic uveitis, and are more likely to have ocular complications. Those in the non-IMT group are more likely to have anterior idiopathic NIU. Baseline visual acuity and panuveitis are the main predictors of final vision outcomes among patients with NIU.

OPTICAL COHERENCE TOMOGRAPHY FEATURES IN IDIOPATHIC NONINFECTIOUS INTERMEDIATE, POSTERIOR, OR PANUVEITIS.

PURPOSE: To characterize optical coherence tomography features in patients with idiopathic intermediate, posterior, or panuveitis. METHODS: This is a retrospective case series of all consecutive cases of idiopathic intermediate, posterior, or panuveitis at four tertiary care centres between 2010 and 2021. RESULTS: A total of 94 eyes (55 patients) were followed for an average duration of 29.8 (SD 21) months. The median central macular thickness was 284 µ m at baseline and 267 µ m at last follow-up. At baseline and last follow-up, respectively, 24% and 20% of uveitic eyes had intraretinal fluid, 12% and 1% subretinal fluid, and 43% and 54% epiretinal membrane. In addition, ellipsoid zone abnormalities on en-face were noted in 34% and 19% of cases at baseline and last follow-up, respectively. The baseline median visual acuity was significantly lower among cases with ellipsoid zone en-face slab abnormalities compared with those without (0.2 logarithm of minimum angle of resolution [interquartile range: 0-0.6] vs. 0.1 logarithm of minimum angle of resolution [interquartile range: 0-0.3], P = 0.0051). CONCLUSION: With initiation of treatment, the central macular thickness, intraretinal fluid, subretinal fluid, and ellipsoid zone en-face abnormalities improved over time, whereas the number of cases with epiretinal membrane increased among eyes with idiopathic intermediate, posterior, and panuveitis. Presence of ellipsoid zone en-face abnormalities at presentation may be associated with worse visual acuity.

Publication Rate of Presentations at a National Physical Medicine and Rehabilitation Scientific Conference From 2009 to 2018.

ABSTRACT: Conferences are important platforms for sharing research, but full-text publication is necessary for broader dissemination and impact. Few studies have examined the abstract-to-publication rate for physical medicine and rehabilitation. This study aimed to determine the abstract-to-publication rate of research abstracts presented from 2009-2018 at the Canadian Association of Physical Medicine and Rehabilitation annual scientific meetings. Using the official book of abstracts from 2009 to 2018, year of conference, abstract title, author names, and the affiliation/level of training of the first author were extracted. Systematic searches of abstract key words, authors' names, and the abstract title were performed using PubMed and Google Scholar to determine whether an abstract proceeded to full-text publication; if so, the date and journal of publication were extracted. Of the 524 total abstracts presented at the Canadian Association of Physical Medicine and Rehabilitation from 2009 to 2018, 187 went on to full-text publication for an abstract-to-publication rate of 35.8%. The mean time to full-text publication was 23.4 ± 8.63 mos. The abstract-to-publication rate was 18.6% for medical students, 28.7% for residents, 41.1% for physical medicine and rehabilitation consultants, and 49.4% for nonphysician presenters. This study highlights that low abstract-to-publication rates for novel research presented at the Canadian Association of Physical Medicine and Rehabilitation disproportionately affects trainees. Further research is needed to identify and remedy barriers to publication.

A Systematic Review on the Association Between Tear Film Metrics and Higher Order Aberrations in Dry Eye Disease and Treatment.

We systematically reviewed published research on dry eye disease and its association with higher order aberrations (HOAs). The purpose of this review was to first determine if an association between tear film metrics and HOAs exists and second to determine if the treatment of dry eyes can improve tear film metrics and HOAs together. A search was conducted in Entrez PubMed on 25 April 2021 using the keywords "higher order aberrations" and "dry eye". The initial search yielded 61 articles. After publications were restricted to only original articles measuring HOA outcomes in patients with dry eye, the final yield was 27 relevant articles. Of these 27 papers, 12 directly looked at associations and correlations between dry eyes and HOA parameters. The remaining 15 studies looked at dry eye interventions and HOA outcomes and parameters. There is clear evidence demonstrating that dry eyes and HOAs have an association, and that the tear film is one of the most important factors in this relationship. There is also a direct correlation between tear film metrics and HOAs. Improvements in HOAs with dry eye interventions provide further evidence to support the intricate relationship between the two. Despite the clear association between HOAs and dry eye disease, further research is still required in the realm of clinical application as dry eye interventions vary depending on many factors, including patient severity and eye drop viscosity.

Use of Gene Therapy in Retinal Ganglion Cell Neuroprotection: Current Concepts and Future Directions.

We systematically reviewed published translational research on gene-based therapy for retinal ganglion cell (RGC) neuroprotection. A search was conducted on Entrez PubMed on 23 December 2020 using the keywords "gene therapy", "retinal ganglion cell" and "neuroprotection". The initial search yielded 82 relevant articles. After restricting publications to those with full text available and in the English language, and then curating for only original articles on gene-based therapy, the final yield was 18 relevant articles. From the 18 papers, 17 of the papers utilized an adeno-associated viral (AAV) vector for gene therapy encoding specific genes of interest. Specifically, six of the studies utilized an AAV vector encoding brain-derived neurotrophic factor (BDNF), two of the studies utilized an AAV vector encoding erythropoietin (EPO), the remaining 10 papers utilized AAV vectors encoding different genes and one microRNA study. Although the literature shows promising results in both in vivo and in vitro models, there is still a significant way to go before gene-based therapy for RGC neuroprotection can proceed to clinical trials. Namely, the models of injury in many of the studies were more acute in nature, unlike the more progressive and neurodegenerative pathophysiology of diseases, such as glaucoma. The regulation of gene expression is also highly unexplored despite the use of AAV vectors in the majority of the studies reviewed. It is also expected that with the successful launch of messenger ribonucleic acid (mRNA)-based vaccinations in 2020, we will see a shift towards this technology for gene-based therapy in glaucoma neuroprotection.

A role for ATP Citrate Lyase in cell cycle regulation during myeloid differentiation.

Differentiation of myeloid progenitor cells into macrophages is accompanied by increased PU.1 concentration and increasing cell cycle length, culminating in cell cycle arrest. Induction of PU.1 expression in a cultured myeloid cell line expressing low PU.1 concentration results in decreased levels of mRNA encoding ATP-Citrate Lyase (ACL) and cell cycle arrest. ACL is an essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis and for histone acetylation. We hypothesized that ACL may play a role in cell cycle regulation in the myeloid lineage. In this study, we found that acetyl-CoA or acetate supplementation was sufficient to rescue cell cycle progression in cultured BN cells treated with an ACL inhibitor or induced for PU.1 expression. Acetyl-CoA supplementation was also sufficient to rescue cell cycle progression in BN cells treated with a fatty acid synthase (FASN) inhibitor. We demonstrated that acetyl-CoA was utilized in both fatty acid synthesis and histone acetylation pathways to promote proliferation. Finally, we found that Acly mRNA transcript levels decrease during normal macrophage differentiation from bone marrow precursors. Our results suggest that regulation of ACL activity is a potentially important point of control for cell cycle regulation in the myeloid lineage.

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism.