Development of a Semi-automated Computer-based Tool for the Quantification of Vascular Tortuosity in the Murine Retina.

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.

The Incidence and Timing of Treatment-Requiring Retinopathy of Prematurity in Nanopremature and Micropremature Infants in the United States: A National Multicenter Retrospective Cohort Study.

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.

Female Representation in Pediatric Ophthalmology at the American Academy of Ophthalmology Annual Meeting From 2018 to 2022.

PURPOSE: To identify trends in female pediatric ophthalmologist authorship and representation at the American Academy of Ophthalmology (AAO) Annual Meeting from 2018 to 2022. METHODS: Participant data from 2018 to 2022 were collected from the AAO website, organized by conference activity (papers, posters, instruction courses, videos, symposia, subspecialty day, and awards), and analyzed by sex using an online tool. Chi-squared and odds ratio analyses were performed to determine trends in authorship sex and associations between the sex of paper and poster authors in each category. RESULTS: Of 923 pediatric ophthalmology presentations from 2018 to 2022, 46.2% (426 of 923) of presenters and 46.6% (281 of 603) of unique individual participants were women. Overall, 48% (174 of 362) of first and senior authors of papers and posters were women. No significant difference or association between female first and senior authors was observed (52% vs 44%, P = .14; odds ratio 1.59, P = .13). There was no significant change in the proportion of total female presenters from 2018 to 2019 (-3.09%, P = .53), 2019 to 2020 (0.76%, P = .88), 2020 to 2021 (9.09%, P = .09), 2021 to 2022 (-5.68%, P = .30), or 2018 to 2022 (1.08%, P = .84). CONCLUSIONS: Since 2018, female representation at the AAO Annual Meeting has remained consistent and nears 50%. The lack of a significant difference between the proportion of female first and senior authors suggests that junior female pediatric ophthalmologists are climbing the ranks and more broadly engaging in mentorship roles. Considering the increasing proportion of female pediatric ophthalmologists, the absence of corollary, statistically significant increases in female participation may be of concern. [J Pediatr Ophthalmol Strabismus. 2024;61(1):6-13.].

Applications of Deep Learning: Automated Assessment of Vascular Tortuosity in Mouse Models of Oxygen-Induced Retinopathy.

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.

Familial Exudative Vitreoretinopathy-Like Phenotype in a Patient With Microcephaly and TUBGCP6 Mutations.

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.

Endophthalmitis caused by Burkholderia cepacia complex (BCC): clinical characteristics, antibiotic susceptibilities, and treatment outcomes.

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.

Retinal Detachments in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Surgical Outcomes.

BACKGROUND AND OBJECTIVE: Retinal detachments (RDs) are a complication of X-linked retinoschisis (XLRS) with a poor prognosis. This study aims to report outcomes of XLRS-RD repair in pediatric patients. MATERIALS AND METHODS: The study is a retrospective analysis of pediatric patients undergoing vitreoretinal surgery for XLRS-RDs from 2000 to 2022. RESULTS: Nine patients (11 eyes) met inclusion criteria. All patients were boys, with a mean age of 8 years. Most RDs arose inferiorly (64%). Seven (64%) detachments were macula-involving. Seven (64%) detachments were repaired with combined scleral buckling and vitrectomy, two (18%) detachments were repaired with vitrectomy alone, one (9%) detachment underwent a primary scleral buckling procedure, and one (9%) asymptomatic detachment with a pigment demarcation line was observed. Silicone oil was used in eight of nine (89%) eyes undergoing vitrectomy. Final visual acuity was 20/200 or better in eight (73%) eyes. One eye that underwent surgical intervention remained unattached at follow-up. CONCLUSION: Surgical repair in patients with XLRSRDs was associated with successful reattachment, although visual prognosis varied. [Ophthalmic Surg Lasers Imaging Retina 2023;54:574-579.].

Endophthalmitis caused by Burkholderia cepacia complex (BCC): Clinical characteristics, antibiotic susceptibilities, and treatment outcomes.

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.

Perspectives of U.S. Ophthalmology Residents and Medical Students on Ophthalmology Exposure during Medical School.

Introduction In recent decades, ophthalmology exposure in medical school has been increasingly reduced. In turn, medical students have expressed concern over their ophthalmic skills. Research investigating the status of ophthalmology education in U.S. undergraduate medical curricula is limited to institutional data devoid of the student or resident perspective. This study seeks to gain a better understanding of current ophthalmology education for U.S. medical students from the trainee point of view. Methods A cross-sectional survey was distributed to current U.S. medical students interested in ophthalmology and U.S. ophthalmology residents. Demographic data, ophthalmology curriculum information, respondent learning preferences, and personal reflections were recorded. Thematic analysis and chi-square tests were utilized. Results In total, 387/4,482 (8.6%) surveys were completed by respondents from 75 U.S. medical institutions. Most respondents were exposed to formal ophthalmology curriculum (63%), research (89%), mentorship (84%), and clinical experiences (87%) during medical school, and medical school curriculum was ranked the third most helpful resource for students to learn about ophthalmology. Yet, 29% of residents ( n = 55) did not feel confident in their diagnostic ophthalmology skills based on their medical school exposure. Student and resident recommendations for improving ophthalmology education delivery commonly referenced nontraditional ophthalmology resources such as online videos ( n = 83) to supplement traditional learning materials such as lectures ( n = 56). Discussion These findings suggest that primary ophthalmology exposure in medical school has shifted toward extracurricular activities such as research and clinical observation. Considering the increasing time demands placed on the medical education system, utilizing nontraditional educational materials to supplement current undergraduate medical education in ophthalmology may provide educators with a resource to improve learner confidence and resident preparedness.

MANAGEMENT OF LARGE OR RECURRENT MACULAR HOLES.

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.