Adverse developmental impacts in progeny of zebrafish exposed to the agricultural herbicide atrazine during embryogenesis.

Atrazine (ATZ) is an herbicide commonly used on crops in the Midwestern US and other select global regions. The US Environmental Protection Agency ATZ regulatory limit is 3 parts per billion (ppb; µg/L), but this limit is often exceeded. ATZ has a long half-life, is a common contaminant of drinking water sources, and is indicated as an endocrine disrupting chemical in multiple species. The zebrafish was used to test the hypothesis that an embryonic parental ATZ exposure alters protein levels leading to modifications in morphology and behavior in developing progeny. Zebrafish embryos (F1) were collected from adults (F0) exposed to 0, 0.3, 3, or 30 ppb ATZ during embryogenesis. Differential proteomics, morphology, and behavior assays were completed with offspring aged 120 or 144 h with no additional chemical treatment. Proteomic analysis identified differential expression of proteins associated with neurological development and disease; and organ and organismal morphology, development, and injury, specifically the skeletomuscular system. Head length and ratio of head length to total length was significantly increased in the F1 of 0.3 and 30 ppb ATZ groups (p < 0.05). Based on molecular pathway alterations, further craniofacial morphology assessment found decreased distance for cartilaginous structures, decreased surface area and distance between saccular otoliths, and a more posteriorly positioned notochord (p < 0.05), indicating delayed ossification and skeletal growth. The visual motor response assay showed hyperactivity in progeny of the 30 ppb treatment group for distance moved and of the 0.3 and 30 ppb treatment groups for time spent moving (p < 0.05). Due to the changes in saccular otoliths, an acoustic startle assay was completed and showed decreased response in the 0.3 and 30 ppb treatments (p < 0.05). These findings suggest that a single embryonic parental exposure alters cellular pathways in their progeny that lead to perturbations in craniofacial development and behavior.

Tendon-derived matrix crosslinking techniques for electrospun multi-layered scaffolds.

Tendon tears are common and healing often occurs incompletely and by fibrosis. Tissue engineering seeks to improve repair, and one approach under investigation uses cell-seeded scaffolds containing biomimetic factors. Retention of biomimetic factors on the scaffolds is likely critical to maximize their benefit, while minimizing the risk of adverse effects, and without losing the beneficial effects of the biomimetic factors. The aim of the current study was to evaluate cross-linking methods to enhance the retention of tendon-derived matrix (TDM) on electrospun poly(ε-caprolactone) (PCL) scaffolds. We tested the effects of ultraviolet (UV) or carbodiimide (EDC:NHS:COOH) crosslinking methods to better retain TDM to the scaffolds and stimulate tendon-like matrix synthesis. Initially, we tested various crosslinking configurations of carbodiimide (2.5:1:1, 5:2:1, and 10:4:1 EDC:NHS:COOH ratios) and UV (30 s 1 J/cm2 , 60 s 1 J/cm2 , and 60 s 4 J/cm2 ) on PCL films compared to un-crosslinked TDM. We found that no crosslinking tested retained more TDM than coating alone (Kruskal-Wallis: p > .05), but that human adipose stem cells (hASCs) spread most on the 60 s 1 J/cm2 UV- and 2.5:1:1 EDC-crosslinked films (Kruskal-Wallis: p < .05). Next, we compared the effects of 60 s 1 J/cm2 UV- and 2.5:1:1 EDC-crosslinked to TDM-coated and untreated PCL scaffolds on hASC-induced tendon-like differentiation. UV-crosslinked scaffolds had greater modulus and stiffness than PCL or TDM scaffolds, and hASCs spread more on UV-crosslinked scaffolds (ANOVA: p < .05). Fourier transform infrared spectra revealed that UV- or EDC-crosslinking TDM did not affect the peaks at wavenumbers characteristic of tendon. Crosslinking TDM to electrospun scaffolds improves tendon-like matrix synthesis, providing a viable strategy for improving retention of TDM on electrospun PCL scaffolds.

Characterizing Progression to Neovascular AMD in Fellow Eyes of Patients Treated With Intravitreal Anti-VEGF Injections.

BACKGROUND AND OBJECTIVE: The purpose of this study was to assess the real-world incidence of conversion to bilateral neovascular age-related macular degeneration (nAMD) following treatment initiation of nAMD in the initial eye. PATIENTS AND METHODS: This was a retrospective cohort of electronic health records from retinal centers across the United States (Vestrum Database) of all patients with unilateral nAMD treated with anti-vascular endothelial growth factor therapy. RESULTS: A total of 22,553 patients with unilateral nAMD were included. Fellow eyes of 8,522 patients (38%) converted to nAMD. Among these, 2,639 (12%), 2,030 (9%), and 1,802 (8%) patients converted in Years 1, 2, and 3, respectively, after diagnosis in the first eye. Fellow eyes had better vision at conversion and 1 year following conversion. CONCLUSIONS: The fellow eye should be monitored at regular intervals to detect signs of neovascularization. Fellow eyes presented with significantly better vision at diagnosis than the initial eye and maintained better visual acuity with less injections. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:123-128.].

REVERSIBLE RETINAL TOXICITY IN A PATIENT TAKING AXITINIB.

PURPOSE: Axitinib (Inlyta, New York, NY) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one previous systemic therapy. A case of bilateral retinal hemorrhages and cotton wool spots associated with axitinib is reported. METHODS: A 62-year-old woman with a 4-year history of renal cell carcinoma with metastases was treated with axitinib at a maximum oral daily dose of 8 mg. Soon after beginning higher dose therapy, she developed blurred vision, floaters, and photopsias. RESULTS: Funduscopic examination of both eyes revealed cotton wool spots and retinal hemorrhages that improved with cessation of therapy. CONCLUSION: Axitinib may be associated with microangiopathic retinal toxicity.

Sociodemographic Factors Influencing Rhegmatogenous Retinal Detachment Presentation and Outcome.

PURPOSE: The impact of sociodemographic factors on the presentation and outcomes of rhegmatogenous retinal detachment (RRD) in the United States has not been described. We analyzed the impact of these factors on the presenting fovea-on or off status of RRD, single operation anatomic success (SOAS) of repair, and postoperative visual acuity (VA). DESIGN: Retrospective, single-center, cohort study. PARTICIPANTS: Participants included 4061 patients from Wills Eye Hospital/Mid Atlantic Retina from February 2015 to February 2020. METHODS: Sociodemographic factors including age, gender, race, and regional mean household income (MHI) as determined by ZIP code were recorded. The VA at baseline and 12 months post-RRD repair was recorded. Multiple regression analysis was used to evaluate the relationship between sociodemographic factors to fovea-on or off presentation of RRD, SOAS, and 12-month VA. MAIN OUTCOME MEASURES: Foveal attachment at presentation of RRD, SOAS, and 12-month VA. RESULTS: Older age (odds ratio [OR], 1.34 per decade, 95% confidence interval [CI], 1.27-1.41, P < 0.001), male gender (OR, 1.27, 95% CI, 1.11-1.45, P < 0.001), non-White race (OR, 2.41, 95% CI, 1.92-3.03, P < 0.001), and lower MHI (OR, 0.94 per $10 000, 95% CI, 0.91-0.98, P = 0.005) were independent risk factors for fovea-off presentation of RD. The need for reoperation to repair RRD within 90 days was independently associated with fovea-off presentation (OR, 1.47, 95% CI, 1.24-1.74, P < 0.001) and non-White race (OR, 1.72, 95% CI, 1.27-2.39, P < 0.001). Finally, 12-month postoperative VA was worse in patients who were fovea-off (P < 0.001), older (P = 0.041), male (P = 0.038), and non-White (P = 0.007) but was not related to MHI (P = 0.24). CONCLUSIONS: These findings reveal associations between the sociodemographic factors and the presentation and outcomes of RRD. Physicians should be aware that socioeconomic disparities can negatively impact the prognosis of patients with RRD. Further study confirming these findings and efforts to mitigate their effects are warranted and will be of interest to the greater ophthalmology community.

Aqueous Chlorhexidine Compared with Povidone-Iodine as Ocular Antisepsis before Intravitreal Injection: A Randomized Clinical Trial.

PURPOSE: Topical povidone-iodine (PI) is widely used as an ocular surface antiseptic for intravitreal injections (IVIs). Although PI is generally well tolerated, it can be associated with significant ocular irritation. Aqueous chlorhexidine (AqCHX) has been described as a possibly better tolerated antimicrobial for ophthalmic procedures. We compared patient pain scores, ocular surface characteristics, and antimicrobial efficacy between PI 5% and AqCHX 0.1% during IVIs. DESIGN: Prospective single-center, randomized clinical trial. PARTICIPANTS: Patients receiving same-day bilateral intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Each patient had 1 eye randomized to PI or AqCHX, and the second eye received the other agent. Both eyes received topical proparacaine 0.5%. MAIN OUTCOME MEASURES: After IVIs, participants rated their pain (Wong-Baker, scale 0-10) for each eye 1 minute after PI or AqCHX instillation and 1 day after the procedure. Each eye was assessed using a standardized quantitative grading system of corneal epitheliopathy (ocular staining score). Microbial swab cultures of the conjunctiva both before instillation of topical antisepsis and 10 minutes after IVIs were given. RESULTS: A total of 100 eyes of 50 patients were included. The mean patient age was 68 years (range, 39-92), and 30 of 50 (60%) were male. Compared with AqCHX, eyes receiving PI had a greater mean pain score immediately after injection (1.44 vs. 0.44, P < 0.001) but not on postprocedure day 1 (1.04 vs. 0.48, P = 0.06). Eyes that received PI had a higher ocular staining score indicating worse corneal epitheliopathy (4.22 vs. 3.10, P < 0.001). There was no difference in rates of positive microbial cultures between groups. There was no difference in rates of adverse events between groups (P = 0.99), and no cases of endophthalmitis occurred. CONCLUSIONS: Povidone-iodine demonstrated greater ocular surface discomfort and corneal epitheliopathy compared with AqCHX during same-day bilateral IVIs. The 2 agents otherwise demonstrated no difference in positive microbial cultures or adverse events. Aqueous chlorhexidine may be a better tolerated alternative to PI for antimicrobial prophylaxis during IVIs for some patients.

Clinical Outcomes of Eyes With Diabetic Macular Edema Switched From Aflibercept to Ranibizumab Therapy.

BACKGROUND AND OBJECTIVE: In 2018, cases of inflammation were reported after intravitreal aflibercept (IVA), which resulted in switches to intravitreal ranibizumab (IVR). The authors' purpose was to evaluate outcomes after switching from IVA to IVR in diabetic macular edema (DME). PATIENTS AND METHODS: Retrospective cohort study. Eyes switched from IVA to IVR for treating DME were included. Data were gathered from three visits before to three visits post-switch. Outcome measures included central subfoveal thickness (CFT) and Snellen visual acuity (VA). RESULTS: There was a statistically significant increase in CFT at the first visit (325 µm ± 234 µm; P = .006) compared to the switch visit, but no difference later visits (268 µm ± 103 µm; P = .32; 284 µm ± 118 µm; P = .11; n = 54). There was no statistically significant change in mean logarithm of the minimum angle of resolution VA between the switch and later visits (0.43 ± 0.38, P = .95; 0.38 ± 0.30, P = .12; 0.41 ± 0.37, P = .69). CONCLUSIONS: The authors observed transient worsening of macular edema in eyes treated for DME when switched from aflibercept to ranibizumab. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:691-697.].

Ocular trauma during COVID-19 stay-at-home orders: a comparative cohort study.

PURPOSE OF REVIEW: The aim of this study was to report characteristics of patients presenting with serious ocular injuries during the COVID-19 stay-at-home orders. RECENT FINDINGS: Of 1058 patients presenting for emergency evaluation during the stay-at-home order, 62 (5.9%) patients [mean (SD) age, 41.1 (19.2) years; 19 (31%) women; 31 (50%) white] presented with severe ocular trauma. The daily mean (SD) number of patients who presented for emergency evaluation decreased from 49.0 (9) to 36.4 (6) during the quarantine (P < 0.001). Patients presenting during the stay-at-home order were less likely to have health insurance [odds ratio (OR), 0.33; 95% confidence interval (95% CI), 0.13-0.90, P = 0.024], more likely to have a delayed presentation (difference, 22.7 h, 95% CI, 5.8-39.5, P < 0.001, more likely to travel farther to seek emergency care (difference, 10.4 miles, 95% CI, 2.6-18.2, P < 0.001) and more likely to have an injury occur at home (OR, 22.8; 95% CI, 9.6-54.2, P < 0.001). Of injuries occurring at home, there was a significant increase in injuries arising from home improvement projects during the stay-at-home order (28 vs. 0%, P = 0.02). SUMMARY: During the COVID-19 pandemic, patients with ocular trauma were more likely to have injuries sustained at home and have additional barriers to care. These changes underscore a need for targeted interventions to optimize emergent eye care during a pandemic.

Outcomes and Complications of In-Office Laser Demarcation of Peripheral Rhegmatogenous Retinal Detachments.

BACKGROUND AND OBJECTIVE: To evaluate the outcomes of in-office laser demarcation (LD) for peripheral rhegmatogenous retinal detachments (RRDs). PATIENTS AND METHODS: This was a retrospective analysis of peripheral RRDs treated with LD. Patient demographics, visual acuity (VA), and RRD characteristics were recorded. Complications requiring additional procedures were recorded. Multiple logistic regression was used to characterize the association of RRD anatomy to treatment complications. RESULTS: A total of 112 eyes of 107 patients were analyzed with mean follow-up of 20 ± 12 months. VA at baseline and last follow-up was equivalent (0.16 logMAR, Snellen equivalent 20/29). Ninety-five (84.8%) eyes were successfully treated without an additional procedure. In multivariate analysis, the presence of VH (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.1-17; P = .04) and RRDs in the inferior 6 clock hours (OR = 6.2; 95% CI, 1.5-29; P = .01) were associated with complications. CONCLUSIONS: LD is successful in treating peripheral RRDs. RRD characteristics less conducive to laser include presence of VH and inferior RRD. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:428-434.].

Effect of Adjuvant Topical Dorzolamide-Timolol vs Placebo in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: Some eyes with neovascular age-related macular degeneration (AMD) have persistent exudation despite frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. Adjuvant therapies that further reduce edema may improve vision outcomes. Objective: To compare the short-term effect of topical dorzolamide-timolol vs placebo in eyes with neovascular AMD that have persistent exudation following intravitreal anti-VEGF injections. Design, Setting, and Participants: Randomized placebo-controlled clinical trial with enrollment from March 1, 2017, through October 30, 2018. Multicenter trial at 4 clinical sites in the United States. Sixty-three patients with neovascular AMD who had persistent exudation despite intravitreal anti-VEGF injections at 4-week, 5-week, or 6-week intervals. Interventions: Patients were randomized to use dorzolamide-timolol or artificial tears for the study duration. They continued to receive the same anti-VEGF drug at the same interval as the 2 visits before enrollment for 3 additional study visits. Main Outcomes and Measures: The primary outcome measure was change in mean central subfield thickness on optical coherence tomography from baseline to visit 3 (approximately 3 months). Secondary measures included change in mean maximum subretinal fluid height, mean maximum pigment epithelial detachment height, and mean visual acuity (VA). Results: This trial included 52 patients. All 27 patients (100%) assigned to dorzolamide-timolol and 23 of 25 (92%) assigned to placebo were analyzed for the primary outcome. Mean (SD) age was 78.4 (7) years, and 34 of 50 patients (68%) were women. Mean (SD) injections were 20.5 (14) (range, 4-58) before enrollment. Mean (SD) baseline logMAR VA was 0.361 (0.26) (approximate Snellen equivalent, 20/50). Comparing the dorzolamide-timolol with placebo group from baseline to visit 3, mean (SD) change in central subfield thickness (primary outcome) was -36.6 (54) µm vs 1.7 (52.3) µm (difference, 30.8; 95% CI, 0.3-61.3; P = .04); secondary outcomes: maximum PED height was -39.1 (65) µm vs 1.1 (16) µm (difference, 39.6; 95% CI, 9.6-69.6; P = .01) and change in VA from baseline to visit 3 was -2.3 (5) vs 0.3 (1) letters (difference, 2.6 letters; 95% CI, -1.9 to 7.1 letters; P = .78). Conclusions and Relevance: These findings suggest use of dorzolamide-timolol in patients with neovascular AMD with persistent exudation resulted in anatomic but not visual acuity improvements compared with placebo at approximately 3 months. Additional clinical trials with longer follow-up and larger sample sizes presumably would be needed to determine the role, if any, of dorzolamide-timolol in neovascular AMD. Trial Registration: ClinicalTrials.gov Identifier: NCT03034772.

Endogenous Bacterial Endophthalmitis: A Five-Year Retrospective Review at a Tertiary Care Academic Center.

PURPOSE: To better characterize the demographics and outcomes of endogenous bacterial endophthalmitis (EBE). METHODS: Retrospective observational case series of 49 eyes of 41 patients with EBE evaluated at a single academic center. RESULTS: Gram stain (p = .395), symptom duration prior to treatment (p = .483), and number of intravitreal antimicrobial injections (p = .421) did not correlate with mean change in VA. There was no significant difference between mean LogMAR VA at initial evaluation (1.7 ± 0.9) and last available follow up (1.4 ± 1.1, p = .15). Patients with bilateral EBE had 7.25 times greater odds of having cancer (95% CI 1.28, 41.14; p = .025). CONCLUSION: EBE in a North American population showed poor visual recovery despite treatment. It was most commonly due to gram-positive bacteria with the most common infectious source being endocarditis. Malignancy should be considered in patients with bilateral EBE.

Trends in Retina Specialist Imaging Utilization from 2012 to 2016 in the United States Medicare Fee-for-Service Population.

PURPOSE: To characterize temporal trends and regional variance in retinal imaging utilization in the United States Medicare fee-for-service population from 2012-2016. DESIGN: Cross-sectional, retrospective database analysis. METHODS: This study addresses office or operating-room based retinal imaging. Our study population included retina specialists, defined as ophthalmologists performing either intravitreal anti-vascular endothelial growth factor injections or posterior segment laser photocoagulation and no neodymium-doped yttrium aluminum garnet laser capsulotomy. We recorded fundus photography, optical coherence tomography (OCT), intravenous fluorescein angiography (IVFA), indocyanine-green angiography, and ophthalmic ultrasound (B-scan) billed in the Medicare fee-for-service population from 2012-2016. Imaging obtained on any platform or device was eligible for inclusion (eg, posterior pole imaging vs ultrawidefield imaging). The main outcome measure was the relative utilization of retinal imaging modalities. RESULTS: National relative utilization of OCT increased from 61.5% in 2012 to 70.5% in 2016 (P < .001), while IVFA fell from 20.9% to 15.1% over the same interval (P < .001). Fundus photography decreased from 14.6% in 2012 to 11.7% in 2016 (P < .001). By 2016, the Midwest region had the highest relative utilization of OCT (75.2%) and lowest of IVFA (12.0%), while the West region had the lowest OCT (68.4%) and highest IVFA (17.0%). CONCLUSIONS: Among retina specialists, OCT usage increased while the utilization of fundus photography and IVFA has declined. The Midwest region had the highest utilization of OCT and lowest of IVFA.

Dacryoadenitis due to gonococcal conjunctivitis complicated by corneal perforation.

Adnexal and periocular involvement in Neisseria gonorrhoeae (NG) infection is rare. This report describes the case of a patient with a delayed diagnosis of gonococcal dacryoadenitis with contiguous conjunctivitis and corneal involvement. She underwent extensive inpatient laboratory and infectious workup but rapidly progressed to corneal perforation requiring emergent penetrating keratoplasty prior to a positive culture confirming the diagnosis. To date, this is the first reported case of ophthalmologic NG infection with associated conjunctivitis, dacryoadenitis, and corneal perforation.

* Meltblown Polymer Fabrics as Candidate Scaffolds for Rotator Cuff Tendon Tissue Engineering.

Various biomaterial technologies are promising for tissue engineering, including electrospinning, but commercial scale-up of throughput is difficult. The goal of the study was to evaluate meltblown fabrics as candidate scaffolds for rotator cuff tendon tissue engineering. Meltblown poly(lactic acid) fabrics were produced with several polymer crystallinities and airflow velocities [500(low), 900(medium) or 1400(high) m3air/h/m fabric]. Fiber diameter, alignment, and baseline bidirectional tensile mechanical properties were evaluated. Attachment and spreading of human adipose-derived stem cells (hASCs) were evaluated over 3 days immediately following seeding. After initial screening, the fabric with the greatest Young's modulus and yield stress was selected for 28-day in vitro culture and for evaluation of tendon-like extracellular matrix production and development of mechanical properties. As expected, airflow velocity of the polymer during meltblowing demonstrated an inverse relationship with fiber diameter. All fabrics exhibited fiber alignment parallel to the direction of collector rotation. All fabrics demonstrated mechanical anisotropy at baseline. Cells attached, proliferated, and spread on all fabrics over the initial three-day culture period. Consistent with the observed loss of integrity of the unseeded biomaterial, hASC-seeded scaffolds demonstrated a significant decrease in Young's modulus over 28 days of culture. However, dsDNA, sulfated glycosaminoglycan, and collagen content increased significantly over 28 days. Histology and polarized light microscopy demonstrated collagen deposition and alignment throughout the thickness of the scaffolds. While fiber diameters approximated an order of magnitude greater than those previously reported for electrospun scaffolds intended for tendon tissue engineering, they were still within the range of collagen fiber diameters found in healthy tendon. The extent of matrix production and alignment was similar to that previously observed for multilayered electrospun scaffolds. While the Young's modulus of scaffolds after 28 days of culture was lower than native rotator cuff tendon, it approximated that reported previously following culture of electrospun scaffolds and was on the same order of magnitude as of current Food and Drug Administration-approved patches for rotator cuff augmentation. Together, these data suggest that with minor polymer and parameter modifications, meltblown scaffolds could provide an economical, high-throughput production alternative method to electrospinning for use in rotator cuff tendon tissue engineering.

Orbital Compartment Syndrome Following Post-Traumatic Subgaleal Hematoma.

Orbital extension of subgaleal hematoma is rare. This report describes the case of an otherwise healthy 10-year-old girl who developed delayed contralateral proptosis and external ophthalmoplegia after relatively minor right-sided forehead trauma. She was found to have bilateral subgaleal hematomas communicating with a left superior subperiostial orbital hematoma. Over the course of 2 days, she developed an orbital compartment syndrome requiring emergent canthotomy and cantholysis, followed by surgical incision and drainage of her scalp hematoma without orbitotomy. Hematologic work-up revealed heterozygous factor VII deficiency.

Periocular, periorbital, and orbital pathology in liver disease.

Although the connection is not often apparent, hepatic pathology may be associated with ophthalmic disease. We review the literature concerning the periocular, periorbital, and orbital manifestations of various hepatic disorders. This includes periocular or periorbital jaundice, the impact of hepatitis B and C, eyelid changes in cirrhosis, orbital mass lesions in hepatocellular carcinoma, and cutaneous vascular malformations as they are related to liver disease. The motility disorders associated with Wilson disease, the ophthalmic manifestations of Alagille syndrome, and the effects of liver transplantation are also discussed.