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Purpose: To describe an open-source dataset of flat-mounted retinal images and vessel segmentations from mice subject to the oxygen-induced retinopathy (OIR) model., Methods: Flat-mounted retinal images from mice killed at postnatal days 12 (P12), P17, and P25 used in prior OIR studies were compiled. Mice subjected to normoxic conditions were killed at P12, P17, and P25, and their retinas were flat-mounted for imaging. Major blood vessels from the OIR images were manually segmented by four graders (JSC, HKR, KBL, JM), with cross-validation performed to ensure similar grading., Results: Overall, 1170 images were included in this dataset. Of these images, 111 were of normoxic mice retina, and 1048 were mice subject to OIR. The majority of images from OIR mice were obtained at P17. The 50 images obtained from an external dataset, OIRSeg, did not have age labels. All images were manually segmented and used in the training or testing of a previously published deep learning algorithm., Conclusions: This is the first open-source dataset of original and segmented flat-mounted retinal images. The dataset has potential applications for expanding the development of generalizable and larger-scale artificial intelligence and analyses for OIR. This dataset is published online and publicly available at dx.doi.org/10.6084/m9.figshare.23690973., Translational Relevance: This open access dataset serves as a source of raw data for future research involving big data and artificial intelligence research concerning oxygen-induced retinopathy.

Participants: This article includes 7293 infants (14 586 eyes) screened for ROP across 5 centers in the United States (Austin Retina Associates, Austin, TX; Bascom Palmer Eye Institute, Miami, FL; Beaumont Eye Institute, Royal Oak, MI; Massachusetts Eye and Ear, Boston, MA; and Stanford Byers Eye Institute, Stanford, CA)., Purpose: To analyze the incidence and timing of treatment requiring retinopathy of prematurity (ROP) in extremely small premature infants. We hypothesize that the smaller the infant by gestational age and birthweight, the higher their likelihood of requiring treatment for ROP., Design: Premature infants screened for Retinopathy of Prematurity from 2002-2022 were divided into cohorts based on the following criteria based on gestational age (GA) and birth weight (BW). "Micropremature infants" are infants born between 24-26 weeks GA and between 600-799 g BW. "Nanopremature infants" are born ≤ 24 weeks GA and ≤ 600 g BW., Methods: Retrospective chart review., Main Outcome Measures: The incidence and timing of treatment-requiring ROP., Results: We found that infants defined as nanopremature had a ∼63% chance of requiring treatment at an average postmenstrual age (PMA) of 36.6 weeks, whereas those defined as micropremature had a 30% chance of requiring treatment at an average PMA of 36.3 weeks. This significantly contrasts with the risk of all screened babies for ROP where the risk of requiring treatment was 8.5%., Conclusion: Micropremature and nanopremature infants are significantly more likely to require treatment for ROP. With demographic data matched to all 5 major US regions spanning the last decade, these results have the potential to inform neonatologists, pediatricians, and ophthalmologists of an important shift in the landscape of prematurity in the United States., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The murine oxygen-induced retinopathy (OIR) model is one of the most widely used animal models of ischemic retinopathy, mimicking hallmark pathophysiology of initial vaso-obliteration (VO) resulting in ischemia that drives neovascularization (NV). In addition to NV and VO, human ischemic retinopathies, including retinopathy of prematurity (ROP), are characterized by increased vascular tortuosity. Vascular tortuosity is an indicator of disease severity, need to treat, and treatment response in ROP. Current literature investigating novel therapeutics in the OIR model often report their effects on NV and VO, and measurements of vascular tortuosity are less commonly performed. No standardized quantification of vascular tortuosity exists to date despite this metric's relevance to human disease. This proof-of-concept study aimed to apply a previously published semi-automated computer-based image analysis approach (iROP-Assist) to develop a new tool to quantify vascular tortuosity in mouse models., Design: Experimental study., Subjects: C57BL/6J mice subjected to the OIR model., Methods: In a pilot study, vasculature was manually segmented on flat-mount images of OIR and normoxic (NOX) mice retinas and segmentations were analyzed with iROP-Assist to quantify vascular tortuosity metrics. In a large cohort of age-matched (postnatal day 12 [P12], P17, P25) NOX and OIR mice retinas, NV, VO, and vascular tortuosity were quantified and compared. In a third experiment, vascular tortuosity in OIR mice retinas was quantified on P17 following intravitreal injection with anti-VEGF (aflibercept) or Immunoglobulin G isotype control on P12., Main Outcome Measures: Vascular tortuosity., Results: Cumulative tortuosity index was the best metric produced by iROP-Assist for discriminating between OIR mice and NOX controls. Increased vascular tortuosity correlated with disease activity in OIR. Treatment of OIR mice with aflibercept rescued vascular tortuosity., Conclusions: Vascular tortuosity is a quantifiable feature of the OIR model that correlates with disease severity and may be quickly and accurately quantified using the iROP-Assist algorithm., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Purpose: To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis., Study Design: Retrospective, observational case series., Methods: Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed wisth culture-confirmed endophthalmitis due to BCC. Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system., Results: Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1 mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%)., Conclusions: Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics., (© 2023. The Author(s).)

Purpose: To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex ( BCC ) associated endophthalmitis., Study Design: Retrospective, observational case series., Methods: Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed with culture-confirmed endophthalmitis due to BCC . Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system., Results: Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%)., Conclusions: Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics., Competing Interests: Declarations Competing interests The authors declare that they have no competing interest.

Objective: To develop a generative adversarial network (GAN) to segment major blood vessels from retinal flat-mount images from oxygen-induced retinopathy (OIR) and demonstrate the utility of these GAN-generated vessel segmentations in quantifying vascular tortuosity., Design: Development and validation of GAN., Subjects: Three datasets containing 1084, 50, and 20 flat-mount mice retina images with various stains used and ages at sacrifice acquired from previously published manuscripts., Methods: Four graders manually segmented major blood vessels from flat-mount images of retinas from OIR mice. Pix2Pix, a high-resolution GAN, was trained on 984 pairs of raw flat-mount images and manual vessel segmentations and then tested on 100 and 50 image pairs from a held-out and external test set, respectively. GAN-generated and manual vessel segmentations were then used as an input into a previously published algorithm (iROP-Assist) to generate a vascular cumulative tortuosity index (CTI) for 20 image pairs containing mouse eyes treated with aflibercept versus control., Main Outcome Measures: Mean dice coefficients were used to compare segmentation accuracy between the GAN-generated and manually annotated segmentation maps. For the image pairs treated with aflibercept versus control, mean CTIs were also calculated for both GAN-generated and manual vessel maps. Statistical significance was evaluated using Wilcoxon signed-rank tests ( P ≤ 0.05 threshold for significance)., Results: The dice coefficient for the GAN-generated versus manual vessel segmentations was 0.75 ± 0.27 and 0.77 ± 0.17 for the held-out test set and external test set, respectively. The mean CTI generated from the GAN-generated and manual vessel segmentations was 1.12 ± 0.07 versus 1.03 ± 0.02 ( P  = 0.003) and 1.06 ± 0.04 versus 1.01 ± 0.01 ( P < 0.001), respectively, for eyes treated with aflibercept versus control, demonstrating that vascular tortuosity was rescued by aflibercept when quantified by GAN-generated and manual vessel segmentations., Conclusions: GANs can be used to accurately generate vessel map segmentations from flat-mount images. These vessel maps may be used to evaluate novel metrics of vascular tortuosity in OIR, such as CTI, and have the potential to accelerate research in treatments for ischemic retinopathies., Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article., (© 2023 by the American Academy of Ophthalmology.)

Purpose: To describe a case of microcephaly, unilateral retinal fold, and familial exudative vitreoretinopathy (FEVR)-like phenotype in the context of 2 TUBGCP6 variants. Methods: A case and its findings were analyzed. Results: A 4-month-old boy with no family history of eye disease presented by referral for management of presumed persistent fetal vasculature in the left eye. An external examination showed microcephaly. The patient grimaced to light in both eyes, and the anterior segments were unremarkable. On dilated fundus examination, diffuse chorioretinal atrophy was present bilaterally. In the left eye, a retinal fold emanated from the optic nerve head. There was early termination of retinal vasculature, especially in zone 3 in the left eye, resembling a FEVR-like phenotype. Panel-based genetic testing was performed and found 2 mutations in TUBGCP6 . Conclusions: Microcephaly, chorioretinopathy, and retinal folds may be associated with TUBGCP6 mutations and masquerade as PFV., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Purpose of Review: To review and critically appraise the recent literature about new surgical techniques for the management of large or recurrent macular holes., Recent Findings: A variety of surgical approaches have recently been developed ranging from autologous retinal grafts to amniotic membrane transplant with varying levels of anatomical and visual success., Summary: More data is needed to determine if one technique is superior to others. However, with a variety of grafts, adhesives, and tamponades at their disposal, vitreoretinal surgeons have an extensive array of options to approach complex macular holes., Competing Interests: Conflict of Interest Hailey Kay Robles-Holmes, Patrick C. Staropoli, and Nicolas Yannuzzi each declare no potential conflicts of interest. Jayanth Sridhar reports personal fees from Alcon, Regeneron, Oxurioin, and Alimera.