Publications

2020

Tripathy K, Ying H, Maldonado Cerda A, Filipowicz A, Kaya M, Seymen Z, Anesi S, Chang P, Foster CS. Widefield Fundus Fluorescein Angiography Features of Uveitis Associated with Juvenile Idiopathic Arthritis. Ocul Immunol Inflamm. 2020;:1–10.
PURPOSE: To evaluate the wide-field fundus fluorescein angiography (WFA) characteristics of uveitis associated with juvenile idiopathic arthritis (JIA-uveitis). METHODS: Retrospective review of records. WFA with Spectralis (Heidelberg) of JIA-uveitis patients were analyzed using the scoring system by Angiography Scoring for Uveitis Nomenclature. RESULTS: Thirty-seven eyes of 20 patients were studied. A total score of at least 1 was noted in 27 eyes (72.97%). WFA features included optic disc hyperfluorescence (51.35%), macular leakage (27.03%), retinal vascular staining/leakage at posterior pole (27.03%) and peripheral retina (64.86%), capillary leakage at the posterior pole (37.84%), and peripheral retina (59.46%). A decision to change the management plan was made in 8 of 9 patients with bilateral quiet anterior chambers after WFA results. CONCLUSION: More than 70% of JIA-uveitis eyes showed some WFA-evidence of posterior segment inflammation, which changed the course of therapy for a major proportion of patients with no clinically active anterior chamber inflammation.
Chen X, Amorim J, Moustafa G, Lee JJ, Yu Z, Ishihara K, Iesato Y, Barbisan P, Ueta T, Togka K, Lu L, Sinclair D, Vavvas D. Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment. Aging (Albany NY). 2020;12.
Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL photoreceptors, CD11b macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.
Moharrer M, Tang X, Luo G. With Motion Perception, Good Visual Acuity May Not Be Necessary for Driving Hazard Detection. Transl Vis Sci Technol. 2020;9(13):18.
Purpose: To investigate the roles of motion perception and visual acuity in driving hazard detection. Methods: Detection of driving hazard was tested based on video and still-frames of real-world road scenes. In the experiment using videos, 20 normally sighted participants were tested under four conditions: with or without motion interruption by interframe mask, and with or without simulated low visual acuity (20/120 on average) by using a diffusing filter. Videos were down-sampled to 2.5 Hz, to allow the addition of motion interrupting masks between the frames to maintain video durations. In addition, single still frames extracted from the videos were shown in random order to eight normally sighted participants, who judged whether the frames were during ongoing hazards, with or without the diffuser. Sensitivity index d-prime (d') was compared between unmasked motion ( = 20) and still frame conditions ( = 8). Results: In the experiment using videos, there was a significant reduction in a combined performance score (taking account of reaction time and detection rate) when the motion was disrupted ( = 0.016). The diffuser did not affect the scores ( = 0.419). The score reduction was mostly due to a decrease in the detection rate ( = 0.002), not the response time ( = 0.148). The d' of participants significantly decreased ( < 0.001) from 2.24 with unmasked videos to 0.68 with still frames. Low visual acuity also had a significant effect on the d' ( = 0.004), but the change was relatively small, from 2.03 without to 1.56 with the diffuser. Conclusions: Motion perception plays a more important role than visual acuity for detecting driving hazards. Translational Relevance: Motion perception may be a relevant criterion for fitness to drive.
Naidoo K, Kempen J, Gichuhi S, Braithwaite T, Casson R, Cicinelli MV, Das A, Flaxman S, Jonas J, Keeffe JE, Leasher J, Limburg H, Pesudovs K, Resnikoff S, Silvester A, Tahhan N, Taylor H, Wong T, Bourne R, Study VLEGGBD. Prevalence and causes of vision loss in sub-Saharan Africa in 2015: magnitude, temporal trends and projections. Br J Ophthalmol. 2020;104(12):1658–1668.
BACKGROUND: This study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020. METHODS: A systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity <3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting distance visual acuity <6/18 but ≥3/60) and mild vision impairment (MVI; presenting distance visual acuity <6/12 and ≥6/18), and also near vision impairment (
Webb L, Chen J, Aksamit A, Bhattacharyya S, Chwalisz B, Balaban D, Manzano G, Ali A, Lord J, Clardy S, Samudralwar R, Mao-Draayer Y, Garrity J, Bhatti T, Turner L, Flanagan E. A multi-center case series of sarcoid optic neuropathy. J Neurol Sci. 2020;:117282.
OBJECTIVE: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes. METHODS: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis. RESULTS: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/μL; range: 1-643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up. CONCLUSIONS: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.
Tsubota K, Pflugfelder S, Liu Z, Baudouin C, Kim HM, Messmer E, Kruse F, Liang L, Carreno-Galeano JT, Rolando M, Yokoi N, Kinoshita S, Dana R. Defining Dry Eye from a Clinical Perspective. Int J Mol Sci. 2020;21(23).
Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: "Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities." The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.
Many of the risk factors for developing severe coronavirus disease 2019 (COVID-19) are also risk factors for eye diseases such as age-related macular degeneration (AMD). During the past decades, macrophages and the complement pathway (as a part of the innate immune system) have been identified as important contributors to the development of AMD, and we suggest that these mechanisms are of similar importance for the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Based on the experience with AMD, we discuss how behavioral factors such as diet, smoking and higher body mass index, as well as genetic determinants such as the complement and immune pathway genes may lead to the overactive inflammatory phenotypes seen in some patients with COVID-19, and may in part explain the heterogeneity of disease manifestations and outcomes. Based on this experience, we discuss potential genetic research projects and elaborate on preventive and treatment approaches related to COVID-19.
Gilmore M, Salamzade R, Selleck E, Bryan N, Mello S, Manson A, Earl A. Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of Enterococcus faecalis. mBio. 2020;11(6).
The enterococci, which are among the leading causes of multidrug-resistant (MDR) hospital infection, are notable for their environmental ruggedness, which extends to intrinsic antibiotic resistance. To identify genes that confer this unique property, we used Tn-seq to comprehensively explore the genome of MDR strain MMH594 for genes important for growth in nutrient-containing medium and with low-level antibiotic challenge. As expected, a large core of genes for DNA replication, expression, and central metabolism, shared with other bacteria, are intolerant to transposon disruption. However, genes were identified that are important to that are either absent from or unimportant for and fitness when similarly tested. Further, 217 genes were identified that when challenged by sub-MIC antibiotic levels exhibited reduced tolerance to transposon disruption, including those previously shown to contribute to intrinsic resistance, and others not previously ascribed this role. is one of the few Gram-positive bacteria experimentally shown to possess a functional Entner-Doudoroff pathway for carbon metabolism, a pathway that contributes to stress tolerance in other microbes. Through functional genomics and network analysis we defined the unusual structure of this pathway in and assessed its importance. These approaches also identified toxin-antitoxin and related systems that are unique and active in Finally, we identified genes that are absent in the closest nonenterococcal relatives, the vagococci, and that contribute importantly to fitness with and without antibiotic selection, advancing an understanding of the unique biology of enterococci. Enterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of general importance for enterococcal survival and growth that distinguish them from closely related pathogens as well as ancestrally related species. We further identified unique traits that enable them to survive antibiotic challenge, revealing a large set of genes that contribute to intrinsic antibiotic resistance and a smaller set of uniquely important genes that are rare outside enterococci.
Sobrin L, Yu Y, Susarla G, Chan W, Xia T, Kempen J, Hubbard R, VanderBeek B. Risk of Noninfectious Uveitis with Female Hormonal Therapy in a Large Healthcare Claims Database. Ophthalmology. 2020;127(11):1558–1566.
PURPOSE: To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan. METHODS: Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed. MAIN OUTCOME MEASURES: Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code. RESULTS: There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95% confidence interval [CI], 0.83-1.17; P = 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95% CI, 1.04-1.41; P = 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95% CI, 1.05-1.45; P = 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged ≥45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95% CI, 1.03-1.47; P = 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged ≤44 years at the time of prescription, but this association did not meet statistical significance (P = 0.20). CONCLUSIONS: Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.