2022

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Xie J, Gao Q, Del Prado ZN, Venkateswaran N, Mousa HM, Salero E, Ye J, De Juan-Pardo EM, Sabater AL, Perez VL. Establishment of a bi-layered tissue engineered conjunctiva using a 3D-printed melt electrowritten poly-(ε-caprolactone) scaffold. Int Ophthalmol 2022;
Xie L, Cen L-P, Li Y, Gilbert H-Y, Strelko O, Berlinicke C, Stavarache MA, Ma M, Wang Y, Cui Q, Kaplitt MG, Zack DJ, Benowitz LI, Yin Y. Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells' response to Pten deletion. Proc Natl Acad Sci U S A 2022;119(15):e2113751119.Abstract
SignificanceThe optic nerve conveys information from retinal ganglion cells (RGCs) to visual processing areas of the brain. Although this pathway normally cannot regenerate when injured nor in degenerative diseases such as glaucoma, this failure can be partially reversed by eliciting a controlled immune reaction in the eye. We show here that the chemokine SDF1 (stromal cell-derived factor 1) is an important contributor to this phenomenon. SDF1 is produced by infiltrative monocytes and acts through its cognate receptor to enhance RGC survival, promote optic nerve regeneration, and sensitize subtypes of RGCs that normally fail to respond to a complementary treatment to exhibit robust, long-distance regeneration. These findings establish SDF1 as an important therapeutic candidate for repairing the injured optic nerve.
Xiong X, Tian S, Yang P, Lebreton F, Bao H, Sheng K, Yin L, Chen P, Zhang J, Qi W, Ruan J, Wu H, Chen H, Breault DT, Wu H, Earl AM, Gilmore MS, Abraham J, Dong M. Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors. Cell 2022;Abstract
Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of β-barrel pore-forming toxins with a β-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E. faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.
Xu J, Emmermann B, Bowers AR. Auditory Reminder Cues to Promote Proactive Scanning on Approach to Intersections in Drivers With Homonymous Hemianopia: Driving With Hemianopia, IX. JAMA Ophthalmol 2022;140(1):75-78.Abstract
Importance: Individuals with homonymous hemianopia (HH) are permitted to drive in some jurisdictions. They could compensate for their hemifield vision loss by scanning toward the blind side. However, some drivers with HH do not scan adequately well to the blind side when approaching an intersection, resulting in delayed responses to hazards. Objective: To evaluate whether auditory reminder cues promoted proactive scanning on approach to intersections. Design, Setting, and Participants: This cross-sectional, single-visit driving simulator study was conducted from October 2018 to May 2019 at a vision rehabilitation research laboratory. A volunteer sample of individuals with HH without visual neglect are included in this analysis. This post hoc analysis was completed in July and August 2020. Main Outcomes and Measures: Participants completed drives with and without scanning reminder cues (a single tone from a speaker on the blind side). Scanning was quantified by the percentage of intersections at which an early large scan was made (a scan with a head movement of at least 20° made before 30 m from the intersection). Responses to motorcycle hazards at intersections were quantified by the time to the first fixation and the time to the horn-press response. Results: Sixteen individuals were recruited and completed the study. Two were subsequently excluded from analyses. Thus, data from 14 participants (median [IQR] age, 54 [36-66] years; 13 men [93%]) were included. Stroke was the primary cause of the HH (10 participants [71%]). Six (43%) had right-sided HH. Participants were more likely to make an early large scan to the blind side in drives with vs without cues (65% vs 45%; difference, 20% [95% CI, 5%-37%]; P < .001). When participants made an early large scan to the blind side, they were faster to make their first fixation on blind-side motorcycles (mean [SD], 1.77 [1.34] vs 3.88 [1.17] seconds; difference, -2.11 [95% CI, -2.46 to -1.75] seconds; P < .001) and faster to press the horn (mean [SD], 2.54 [1.19] vs 4.54 [1.37] seconds; difference, -2.00 [95% CI, -2.38 to -1.62] seconds; P < .001) than when they did not make an early scan. Conclusions and Relevance: This post hoc analysis suggests that auditory reminder cues may promote proactive scanning, which may be associated with faster responses to hazards. This hypothesis should be considered in future prospective studies.
Xu J, Baliutaviciute V, Swan G, Bowers AR. Driving With Hemianopia X: Effects of Cross Traffic on Gaze Behaviors and Pedestrian Responses at Intersections. Front Hum Neurosci 2022;16:938140.Abstract
Purpose: We conducted a driving simulator study to investigate the effects of monitoring intersection cross traffic on gaze behaviors and responses to pedestrians by drivers with hemianopic field loss (HFL). Methods: Sixteen HFL and sixteen normal vision (NV) participants completed two drives in an urban environment. At 30 intersections, a pedestrian ran across the road when the participant entered the intersection, requiring a braking response to avoid a collision. Intersections with these pedestrian events had either (1) no cross traffic, (2) one approaching car from the side opposite the pedestrian location, or (3) two approaching cars, one from each side at the same time. Results: Overall, HFL drivers made more (p < 0.001) and larger (p = 0.016) blind- than seeing-side scans and looked at the majority (>80%) of cross-traffic on both the blind and seeing sides. They made more numerous and larger gaze scans (p < 0.001) when they fixated cars on both sides (compared to one or no cars) and had lower rates of unsafe responses to blind- but not seeing-side pedestrians (interaction, p = 0.037). They were more likely to demonstrate compensatory blind-side fixation behaviors (faster time to fixate and longer fixation durations) when there was no car on the seeing side. Fixation behaviors and unsafe response rates were most similar to those of NV drivers when cars were fixated on both sides. Conclusion: For HFL participants, making more scans, larger scans and safer responses to pedestrians crossing from the blind side were associated with looking at cross traffic from both directions. Thus, cross traffic might serve as a reminder to scan and provide a reference point to guide blind-side scanning of drivers with HFL. Proactively checking for cross-traffic cars from both sides could be an important safety practice for drivers with HFL.
Xu BY, Friedman DS, Foster PJ, Jiang Y, Porporato N, Pardeshi AA, Jiang Y, Munoz B, Aung T, He M. Ocular Biometric Risk Factors for Progression of Primary Angle Closure Disease: The Zhongshan Angle Closure Prevention Trial. Ophthalmology 2022;129(3):267-275.Abstract
PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective, observational study. PARTICIPANTS: Six hundred forty-three mainland Chinese with untreated PACS. METHODS: Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Six-year progression from PACS to PAC or AAC. RESULTS: Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 μm from the scleral spur (AOD500; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72). CONCLUSIONS: Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.
Xu C, Prager AJ, Alonso CD, Pawar AS. Insights From the Eye for Patients With Kidney Transplant. Transplant Proc 2022;Abstract
The eye and the kidney share structural and developmental similarities on a cellular and clinical level, and they are often affected by the same disease processes. Performing an eye exam to look for signs of conditions such as hypertension and diabetes can provide a helpful window into the health of the kidney. Patients with kidney transplants (KT) are a unique population that require close monitoring. These patients are maintained on a number of immunosuppressive medications and may face complications such as medication side effects, infections, and graft rejection. Patients with KT are at higher risk of both infectious and noninfectious eye conditions related to underlying systemic disease or use of immunosuppressive medications. Screening for eye conditions is important because preserving visual function is integral to quality of life, and also because the eye exam can help with early detection and treatment of systemic conditions. Here we describe some of the common eye findings and conditions in patients with KT. We recommend that patients with KT receive annual eye exams, and we hope that the information provided here can help nephrologists become more familiar with eye findings and identify situations where a referral to ophthalmology is warranted.
Xu C, Chen TC, Chodosh J, Eliott D, Mukai S, Shen LQ, Vavvas DG, Young LH, Lin MM. Endoscopic Cyclophotocoagulation in Boston Keratoprosthesis Type II. Ophthalmol Glaucoma 2022;5(1):120-123.
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Yang L, Xiao A, Li Q-Y, Zhong H-F, Su T, Shi W-Q, Ying P, Liang R-B, Xu S-H, Shao Y, Zhou Q. Hyperintensities of middle frontal gyrus in patients with diabetic optic neuropathy: a dynamic amplitude of low-frequency fluctuation study. Aging (Albany NY) 2022;14(3):1336-1350.Abstract
Diabetic optic neuropathy (DON) is a diverse complication of diabetes and its pathogenesis has not been fully elucidated. The purpose of this study was to explore dynamic cerebral activity changes in DON patients using dynamic amplitude of low-frequency fluctuation (dALFF). In total, 22 DON patients and 22 healthy controls were enrolled. The dALFF approach was used in all participants to investigate dynamic intrinsic brain activity differences between the two groups. Compared with HCs, DON patients exhibited significantly increased dALFF variability in the right middle frontal gyrus (P < 0.01). Conversely, DON patients exhibited obviously decreased dALFF variability in the right precuneus (P < 0.01). We also found that there were significant negative correlations between HADS scores and dALFF values of the right middle frontal gyrus in the DON patients (r = -0.6404, P <0.01 for anxiety and r = -0.6346, P <0.01 for depression; HADS, Hospital Anxiety and Depression Scale). Abnormal variability of dALFF was observed in specific areas of the cerebrum in DON patients, which may contribute to distinguishing patients with DON from HCs and a better understanding of DON, hyperintensities of right middle frontal gyrus may be potential diagnostic marker for DON.
Yang S-A, Mitchell WG, Hall N, Elze T, Miller JW, Lorch AC, Zebardast N. Usage Patterns of Minimally Invasive Glaucoma Surgery (MIGS) Differ by Glaucoma Type: IRIS Registry Analysis 2013-2018. Ophthalmic Epidemiol 2021;:1-9.Abstract
Purpose: To examine patterns of standard (trabeculectomy or glaucoma drainage devices, GDDs) vs novel (minimally invasive glaucoma surgery, MIGS) surgical techniques in the US.Methods: We used the American Academy of Ophthalmology (AAO) IRIS® Registry (Intelligent Research in Sight) queried between 2013 and 2018 (inclusive) to calculate the cumulative proportion of stand-alone, concurrent (same day) or sequential (subsequent day) glaucoma surgical techniques performed in each glaucoma diagnosis type. Secondary analyses of adjusted proportions of concurrent and sequential surgeries stratified by glaucoma diagnosis were also performed.Results: Of 203,146 eyes receiving glaucoma surgeries, open angle glaucoma (OAG) was most likely to undergo all types of intervention. The iStent was the most commonly performed MIGS, primarily for those with normal tension glaucoma (NTG) or OAG (p < .001). Conversely, GDD was the most commonly performed procedure in secondary glaucoma or other (specified) glaucoma (p < .001). ECP and iStent were the most common concurrent procedures performed; most often for OAG and NTG (p < .001). After an initial standard surgery, most eyes underwent recurrent standard interventions (90.3%). ECP was the most common MIGS performed after an initial standard surgery; particularly in primary angle-closure (PACG) and secondary glaucoma eyes (p < .001).Conclusion: Glaucoma type may influence the choice of glaucoma procedures and the decision to perform concurrent as well sequential surgical procedures. Given the poorly understood long term safety and effectiveness of MIGS, and with substantially increasing use of MIGS procedures in recent years, future studies comparing their safety and effectiveness vs standard interventions, for a variety of glaucoma types, is needed.
Yang M, Lennikov A, Chang K, Ashok A, Lee C, Cho K-S, Utheim TP, Dartt DA, Chen DF. Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface. BMC Ophthalmol 2022;22(1):490.Abstract
PURPOSE: Transcorneal electrical stimulation (TcES) is increasingly applied as a therapy for preserving and improving vision in retinal neurodegenerative and ischemic disorders. However, a common complaint about TcES is its induction of eye pain and dryness in the clinic, while the mechanisms remain unknown. METHOD: TcES or transpalpebral ES (TpES) was conducted in C57BL6j mice for 14 days. The contralateral eyes were used as non-stimulated controls. Levels of intracellular [Ca2+] ([Ca2+]i) were assessed by Fura-2AM. The conductance resistances of the eye under various ES conditions were measured in vivo by an oscilloscope. RESULTS: Although TcES did not affect tear production, it significantly induced damage to the ocular surface, as revealed by corneal fluorescein staining that was accompanied by significantly decreased mucin (MUC) 4 expression compared to the control. Similar effects of ES were detected in cultured primary corneal epithelium cells, showing decreased MUC4 and ZO-1 levels after the ES in vitro. In addition, TcES decreased secretion of MUC5AC from the conjunctiva in vivo, which was also corroborated in goblet cell cultures, where ES significantly attenuated carbachol-induced [Ca2+]i increase. In contrast to TcES, transpalpebral ES (TpES) did not induce corneal fluorescein staining while significantly increasing tear production. Importantly, the conductive resistance from orbital skin to the TpES was significantly smaller than that from the cornea to the retina in TcES. CONCLUSION: TcES, but not TpES, induces corneal epithelial damage in mice by disrupting mucin homeostasis. TpES thus may represent a safer and more effective ES approach for treating retinal neurodegeneration clinically.
Yang M, Fjærvoll HK, Fjærvoll KA, Wang NH, Utheim TP, Serhan CN, Dartt DA. Sex-based differences in conjunctival goblet cell responses to pro-inflammatory and pro-resolving mediators. Sci Rep 2022;12(1):16305.Abstract
Many conjunctival inflammatory diseases differ between the sexes and altered conjunctival goblet cells (CGCs) response is often involved. Inflammation is initiated by the release of pro-inflammatory mediators and terminated by the biosynthesis of specialized pro-resolution mediators (SPMs). Herein, we determined the sex-based difference in the responses of CGCs to inflammatory stimuli or pro-resolving lipid SPMs and their interaction with sex hormones. GCs were cultured from pieces of human conjunctiva in RPMI media. CGCs were transferred 24 h before the start of experiments to phenol red-free and FBS-free media to minimize exogenous hormones. RT-PCR, immunofluorescence microscopy (IF), and Western Blot (WB) were performed to determine the presence of sex hormone receptors. Cellular response to pro-inflammatory stimuli or SPMs was studied by measuring the increase in intracellular [Ca2+] ([Ca2+]i) using fura 2/AM microscopy. Use of RT-PCR demonstrated estrogen receptor (ER) α in 4/5 males and 3/3 females; ERβ in 2/4 males and 2/3 females; and androgen receptors (AR) in 3/3 male and 3/3 female CGCs. Positive immunoreactivity by IF and protein expression by WB was detected using antibodies for the ERα and ERβ in 3/3 males and 3/3 females, while AR were only present in males. Significantly different Ca2+ responses between sexes were found with carbachol only at 10-3 M, but not with histamine or leukotriene (LT) B4 at any concentration used. Incubation with dihydrotestosterone (DHT), estrone (E1), or estradiol (E2) at 10-7 M for 30 min significantly inhibited the LTB4-stimulated [Ca2+]i increase in male and female CGCs. Incubation with DHT, E1, and E2 overnight significantly inhibited the LTB4 response in females, while DHT and E2 significantly inhibited the LTB4 response in males. The SPM lipoxin A4 (LXA4) (10-9-10-8 M), but not the resolvins D1 or D2, induced an [Ca2+]i increase that was significantly higher in males compared to females. We conclude that male and female CGCs showed differences in the expression of sex hormone receptors. Treatment with sex hormones altered pro-inflammatory mediator LTB4-induced response. Males compared to females have a higher response to the ω-6-fatty acid derived SPM LXA4, indicating males may terminate inflammation in conjunctival goblet cells faster than females.
Yannuzzi NA, Watane A, Patel NA, Townsend JH. Haptic and optic-haptic junction structural integrity of two 3-piece intraocular lenses. J Cataract Refract Surg 2022;48(6):743-744.
Yeung V, Zhang TC, Yuan L, Parekh M, Cortinas JA, Delavogia E, Hutcheon AEK, Guo X, Ciolino JB. Extracellular Vesicles Secreted by Corneal Myofibroblasts Promote Corneal Epithelial Cell Migration. Int J Mol Sci 2022;23(6)Abstract
Corneal epithelial wound healing is a multifaceted process that encompasses cell proliferation, migration, and communication from the corneal stroma. Upon corneal injury, bidirectional crosstalk between the epithelium and stroma via extracellular vesicles (EVs) has been reported. However, the mechanisms by which the EVs from human corneal keratocytes (HCKs), fibroblasts (HCFs), and/or myofibroblasts (HCMs) exert their effects on the corneal epithelium remain unclear. In this study, HCK-, HCF-, and HCM-EVs were isolated and characterized, and human corneal epithelial (HCE) cell migration was assessed in a scratch assay following PKH26-labeled HCK-, HCF-, or HCM-EV treatment. HCE cells proliferative and apoptotic activity following EV treatment was assessed. HCF-/HCM-EVs were enriched for CD63, CD81, ITGAV, and THBS1 compared to HCK-EV. All EVs were negative for GM130 and showed minimal differences in biophysical properties. At the proteomic level, we showed HCM-EV with a log &gt;two-fold change in CXCL6, CXCL12, MMP1, and MMP2 expression compared to HCK-/HCF-EVs; these proteins are associated with cellular movement pathways. Upon HCM-EV treatment, HCE cell migration, velocity, and proliferation were significantly increased compared to HCK-/HCF-EVs. This study concludes that the HCM-EV protein cargo influences HCE cell migration and proliferation, and understanding these elements may provide a novel therapeutic avenue for corneal wound healing.
Yonamine S, Ton L, Rose-Nussbaumer J, Ying G-S, Ahmed IIK, Chen TC, Weiner A, Gedde SJ, Han Y. Survey of the American Glaucoma Society Membership on Current Glaucoma Drainage Device Placement and Postoperative Corticosteroid Use. Clin Ophthalmol 2022;16:2305-2310.Abstract
Purpose: To assess practice patterns and opinions of glaucoma specialists regarding glaucoma drainage device tube shunt placement and post-operative anti-inflammatory medication use. We also assess the perceived need for a randomized control trial to compare them. Patients and Methods: An online survey was distributed to a group of glaucoma specialists from the American Glaucoma Society via the American Glaucoma Society forum from April to August 2021. Results: One hundred and twenty-eight responses were included. Ninety percent placed tubes in the anterior chamber. Sixty-one percent reported that evidence suggested the superiority of sulcus tube placement over the anterior chamber, whereas 34% reported there was not enough evidence to suggest superiority of either in preventing endothelial cell loss. Comparing these techniques for intraocular pressure control, 49% reported evidence suggested sulcus tube placement superiority whereas 46% reported there was not enough evidence. Over 40% of respondents reported that they were either unfamiliar with literature or that there was not enough evidence to support the superiority of difluprednate 0.05% over prednisolone 1% for post-operative use in preventing endothelial cell loss and for intraocular pressure control. Ninety percent and 81% of respondents respectively would benefit from randomized control trials comparing outcomes of anterior chamber vs sulcus tube placement and post-operative corticosteroid usage. Conclusion: Most glaucoma specialists surveyed place glaucoma drainage device tube in the anterior chamber over the sulcus. A randomized control trial to determine optimal tube placement and post-operative anti-inflammatory medication use for preventing endothelial cell loss would change current glaucoma drainage device practice patterns.
Young AK, VanderVeen DK. Controversies in Pediatric Angle Surgery and Secondary Surgical Treatment. Semin Ophthalmol 2022;:1-7.Abstract
Pediatric glaucoma is a constellation of challenging ophthalmic conditions that, left untreated, can result in irreversible vision loss. The mainstay of treatment for primary congenital glaucoma and select secondary glaucoma subtypes is angle surgery, either trabeculotomy or goniotomy. More recently, MIGS devices have been utilized to enhance the efficacy of these procedures. Despite the high success rates of these primary surgical options, refractory cases are challenging to manage. There is no consensus on the next step of treatment following primary angle surgery. Glaucoma drainage devices and trabeculectomies have been the traditional options, with laser treatment reserved for more severe cases. The benefits and disadvantages of each of these options are discussed.
Yousefi S, Pasquale LR, Boland MV, Johnson CA. Machine-identified Patterns of Visual Field Loss and An Association with Rapid Progression in the Ocular Hypertension Treatment Study. Ophthalmology 2022;Abstract
PURPOSE: To identify patterns of visual field (VF) loss based on unsupervised machine learning and to identify patterns that are associated with rapid progression. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: A total of 2231 abnormal VFs from 205 eyes of 176 OHTS participants followed over approximately 16 years. METHODS: VFs were assessed by an unsupervised deep archetypal analysis algorithm as well as an OHTS certified VF reader to identify prevalent patterns of VF loss. Machine-identified patterns of glaucoma damage were compared against those patterns previously identified (expert-identified) in the OHTS in 2003. Based on the longitudinal VFs of each eye, VF loss patterns that were strongly associated with rapid glaucoma progression were identified. MAIN OUTCOME MEASURES: Machine-expert correspondence and type of patterns of VF loss associated with rapid progression. RESULTS: The average VF mean deviation (MD) at conversion to glaucoma was -2.7 dB (Standard Deviation (SD) = 2.4 dB) while the average MD of the eyes at the last visit was -5.2 dB (SD = 5.5 dB). Fifty out of 205 eyes had MD rate of -1 dB/year or worse and were considered rapid progressors. Eighteen machine-identified patterns of VF loss were compared with expert-identified patterns in which 13 patterns of VF loss were similar. The most prevalent expert-identified patterns included partial arcuate, paracentral, and nasal step defects, and the most prevalent machine-identified patterns included temporal wedge, partial arcuate, nasal step, and paracentral VF defects. One of the machine-identified patterns of VF loss predicted future rapid VF progression after adjustment for age, sex, and initial MD. CONCLUSIONS: An automated machine learning system can identify patterns of VF loss and could provide objective, and reproducible nomenclature for characterizing early signs of visual defects and rapid progression in patients with glaucoma.
Yu G, Seto BK, Yamada K, Zeng K, Arroyo JG. COMBINED PNEUMATIC AND ENZYMATIC VITREOLYSIS FOR SEVERE CASES OF VITREOMACULAR TRACTION. Retin Cases Brief Rep 2022;16(5):631-636.Abstract
PURPOSE: To evaluate the efficacy of combined pneumatic and enzymatic vitreolysis for treatment of severe cases of vitreomacular traction (VMT). METHODS: We analyzed a retrospective, consecutive series of five patients diagnosed with severe VMT refractory to pneumatic vitreolysis who then received an additional ocriplasmin injection while their gas bubble from pneumatic vitreolysis was still present between February 2015 and February 2019. Vitreomacular traction release was confirmed using spectral-domain optical coherence tomography. RESULTS: Four of the five patients treated with combined pneumatic and enzymatic vitreolysis achieved VMT release by Day 28, and all cases eventually achieved complete VMT release. In addition to having VMT refractory to pneumatic vitreolysis, patient characteristics included broad adhesion diameter (>1,500 µ m, n = 1), presence of epiretinal membrane (n = 2), age >65 years (n = 4), and pseudophakia (n = 1). The visual acuity improved by three or more lines at 6 months in both of the patients with initial vision worse than 20/50 on an Early Treatment Diabetic Retinopathy Study chart but not in those whose vision was already fairly good (i.e., visual acuity >20/60). None of the patients experienced the following complications after receiving this combined treatment: retinal tears or detachments, vitreous floaters, and ellipsoid zone changes. CONCLUSION: Sequential, combined pneumatic and enzymatic vitreolysis resulted in VMT release in all 5 cases (4 cases by 28 days) and may be a potentially useful alternative to surgical intervention for refractory VMT cases.
Yu Z, Correa VSMC, Efstathiou NE, Albertos-Arranz H, Chen XH, Ishihara K, Iesato Y, Narimatsu T, Ntentakis D, Vavvas DG. UVA induces retinal photoreceptor cell death via receptor interacting protein 3 kinase mediated necroptosis. Cell Death Discov 2022;8(1):489.Abstract
Ultraviolet light A (UVA) is the only UV light that reaches the retina and can cause indirect damage to DNA via absorption of photons by non-DNA chromophores. Previous studies demonstrate that UVA generates reactive oxygen species (ROS) and leads to programmed cell death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor interacting protein 1 and 3 (RIPK1 and RIPK3) kinases, key signaling molecules of PCD, in UVA-induced photoreceptor injury using in vitro and ex vivo models. UVA irradiation activated RIPK3 but not RIPK1 and mediated necroptosis through MLKL that lie downstream of RIPK3 and induced apoptosis through increased oxidative stress. Moreover, RIPK3 but not RIPK1 inhibition suppresses UVA-induced cell death along with the downregulation of MLKL and attenuates the levels of oxidative stress and DNA fragmentation. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced necroptosis cell death in photoreceptors and highlight RIPK3 potential as a neuroprotective target.
Yu-Wai-Man P, Newman NJ, Carelli V, La Morgia C, Biousse V, Bandello FM, Clermont CV, Campillo LC, Leruez S, Moster ML, Cestari DM, Foroozan R, Sadun A, Karanjia R, Jurkute N, Blouin L, Taiel M, Sahel J-A, Sahel J-A. Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study. Eye (Lond) 2022;36(4):818-826.Abstract
BACKGROUND/OBJECTIVES: REALITY is an international observational retrospective registry of LHON patients evaluating the visual course and outcome in Leber hereditary optic neuropathy (LHON). SUBJECTS/METHODS: Demographics and visual function data were collected from medical charts of LHON patients with visual loss. The study was conducted in 11 study centres in the United States of America and Europe. The collection period extended from the presymptomatic stage to at least more than one year after onset of vision loss (chronic stage). A Locally Weighted Scatterplot Smoothing (LOWESS) local regression model was used to analyse the evolution of best-corrected visual acuity (BCVA) over time. RESULTS: 44 LHON patients were included; 27 (61%) carried the m.11778G>A ND4 mutation, 8 (18%) carried the m.3460G>A ND1 mutation, and 9 (20%) carried the m.14484T>C ND6 mutation. Fourteen (32%) patients were under 18 years old at onset of vision loss and 5 (11%) were below the age of 12. The average duration of follow-up was 32.5 months after onset of symptoms. At the last observed measure, mean BCVA was 1.46 LogMAR in ND4 patients, 1.52 LogMAR in ND1 patients, and 0.97 LogMAR in ND6 patients. The worst visual outcomes were reported in ND4 patients aged at least 15 years old at onset, with a mean BCVA of 1.55 LogMAR and no tendency for spontaneous recovery. The LOESS modelling curve depicted a severe and permanent deterioration of BCVA. CONCLUSIONS: Amongst LHON patients with the three primary mtDNA mutations, adult patients with the m.11778G>A ND4 mutation had the worst visual outcomes, consistent with prior reports.

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