Occlusive Vasculitis Following Intravitreal Rituximab Injection for Primary Vitreoretinal Lymphoma.

PURPOSE: We report three cases of occlusive vasculitis following intravitreal rituximab therapy for biopsy-proven primary vitreoretinal lymphoma (PVRL), one of which was following an injection of the biosimilar Riabni (rituximab-arrx, AmGen) and two of which were following an injection of Rituxan (rituximab, Genentech). METHODS: Case series. RESULTS: Three cases of occlusive vasculitis confirmed with fluorescein angiography are reported 5 days, 8 days, and 3.5 weeks following intravitreal injection of rituximab. The initial vision was poor (20/500, 20/150, and light perception), but vision recovered to baseline in two cases, and remained poor in the case of combined artery and vein occlusion. CONCLUSION: Occlusive vasculitis is a rarely reported but potential complication of intravitreal rituximab therapy in patients who have been previously treated with the agent and may have delayed onset. A low threshold for fluorescein angiography as a diagnostic test for post-injection vision loss and prompt treatment with topical and/or oral steroids should be considered.

Myopic Traction Maculopathy in Low Myopia.

We describe a case of myopic traction maculopathy (MTM) in a patient with low myopia that resolved with surgical intervention. Our patient demonstrated no other features of myopic degeneration and none of the typical tractional elements that cause MTM, such as vitreomacular traction due to partial posterior vitreous detachment (PVD) with vitreomacular adhesion, epiretinal membrane, or a remnant cortical vitreous layer following PVD. Possible pathogenic mechanisms in our patient include reduced compliance of the aging internal limiting membrane and/or traction from elasticity within the thin cortical vitreous layer that forms the posterior wall of the premacular liquefied pocket. [Ophthalmic Surg Lasers Imaging Retina 2023;54:481-484.].

Efficacy of Smartphone-Based Telescreening for Retinopathy of Prematurity With and Without Artificial Intelligence in India.

Importance: Retinopathy of prematurity (ROP) telemedicine screening programs have been found to be effective, but they rely on widefield digital fundus imaging (WDFI) cameras, which are expensive, making them less accessible in low- to middle-income countries. Cheaper, smartphone-based fundus imaging (SBFI) systems have been described, but these have a narrower field of view (FOV) and have not been tested in a real-world, operational telemedicine setting. Objective: To assess the efficacy of SBFI systems compared with WDFI when used by technicians for ROP screening with both artificial intelligence (AI) and human graders. Design, Setting, and Participants: This prospective cross-sectional comparison study took place as a single-center ROP teleophthalmology program in India from January 2021 to April 2022. Premature infants who met normal ROP screening criteria and enrolled in the teleophthalmology screening program were included. Those who had already been treated for ROP were excluded. Exposures: All participants had WDFI images and from 1 of 2 SBFI devices, the Make-In-India (MII) Retcam or Keeler Monocular Indirect Ophthalmoscope (MIO) devices. Two masked readers evaluated zone, stage, plus, and vascular severity scores (VSS, from 1-9) in all images. Smartphone images were then stratified by patient into training (70%), validation (10%), and test (20%) data sets and used to train a ResNet18 deep learning architecture for binary classification of normal vs preplus or plus disease, which was then used for patient-level predictions of referral warranted (RW)- and treatment requiring (TR)-ROP. Main Outcome and Measures: Sensitivity and specificity of detection of RW-ROP, and TR-ROP by both human graders and an AI system and area under the receiver operating characteristic curve (AUC) of grader-assigned VSS. Sensitivity and specificity were compared between the 2 SBFI systems using Pearson χ2testing. Results: A total of 156 infants (312 eyes; mean [SD] gestational age, 33.0 [3.0] weeks; 75 [48%] female) were included with paired examinations. Sensitivity and specificity were not found to be statistically different between the 2 SBFI systems. Human graders were effective with SBFI at detecting TR-ROP with a sensitivity of 100% and specificity of 83.49%. The AUCs with grader-assigned VSS only were 0.95 (95% CI, 0.91-0.99) and 0.96 (95% CI, 0.93-0.99) for RW-ROP and TR-ROP, respectively. For the AI system, the sensitivity of detecting TR-ROP sensitivity was 100% with specificity of 58.6%, and RW-ROP sensitivity was 80.0% with specificity of 59.3%. Conclusions and Relevance: In this cross-sectional study, 2 different SBFI systems used by technicians in an ROP screening program were highly sensitive for TR-ROP. SBFI systems with AI may be a cost-effective method to improve the global capacity for ROP screening.

A Platform for Tracking Surgeon and Observer Gaze as a Surrogate for Attention in Ophthalmic Surgery.

Purpose: To develop and validate a platform that can extract eye gaze metrics from surgeons observing cataract and vitreoretinal procedures and to enable post hoc data analysis to assess potential discrepancies in eye movement behavior according to surgeon experience. Design: Experimental, prospective, single-center study. Participants: Eleven ophthalmic surgeons observing deidentified vitreoretinal and cataract surgical procedures performed at a single university-based medical center. Methods: An open-source platform was developed to extract gaze coordinates and metrics from ophthalmic surgeons via a computer vision algorithm in conjunction with a neural network to track and segment instruments and tissues, identifying areas of attention in the visual field of study subjects. Eleven surgeons provided validation data by watching videos of 6 heterogeneous vitreoretinal and cataract surgical phases. Main Outcome Measures: Accuracy and distance traveled by the eye gaze of participants and overlap of the participants' eye gaze with instruments and tissues while observing surgical procedures. Results: The platform demonstrated repeatability of > 94% when acquiring the eye gaze behavior of subjects. Attending ophthalmic surgeons and clinical fellows exhibited a lower overall cartesian distance traveled in comparison to resident physicians in ophthalmology (P < 0.02). Ophthalmology residents and clinical fellows exhibited more fixations to the display area where surgical device parameters were superimposed than attending surgeons (P < 0.05). There was a trend toward gaze overlap with the instrument tooltip location among resident physicians in comparison to attending surgeons and fellows (41.42% vs. 34.8%, P > 0.2). The number and duration of fixations did not vary substantially among groups (P > 0.3). Conclusions: The platform proved effective in extracting gaze metrics of ophthalmic surgeons. These preliminary data suggest that surgeon gaze behavior differs according to experience.

Feature Tracking and Segmentation in Real Time via Deep Learning in Vitreoretinal Surgery: A Platform for Artificial Intelligence-Mediated Surgical Guidance.

PURPOSE: This study investigated whether a deep-learning neural network can detect and segment surgical instrumentation and relevant tissue boundaries and landmarks within the retina using imaging acquired from a surgical microscope in real time, with the goal of providing image-guided vitreoretinal (VR) microsurgery. DESIGN: Retrospective analysis via a prospective, single-center study. PARTICIPANTS: One hundred and one patients undergoing VR surgery, inclusive of core vitrectomy, membrane peeling, and endolaser application, in a university-based ophthalmology department between July 1, 2020, and September 1, 2021. METHODS: A dataset composed of 606 surgical image frames was annotated by 3 VR surgeons. Annotation consisted of identifying the location and area of the following features, when present in-frame: vitrector-, forceps-, and endolaser tooltips, optic disc, fovea, retinal tears, retinal detachment, fibrovascular proliferation, endolaser spots, area where endolaser was applied, and macular hole. An instance segmentation fully convolutional neural network (YOLACT++) was adapted and trained, and fivefold cross-validation was employed to generate metrics for accuracy. MAIN OUTCOME MEASURES: Area under the precision-recall curve (AUPR) for the detection of elements tracked and segmented in the final test dataset; the frames per second (FPS) for the assessment of suitability for real-time performance of the model. RESULTS: The platform detected and classified the vitrector tooltip with a mean AUPR of 0.972 ± 0.009. The segmentation of target tissues, such as the optic disc, fovea, and macular hole reached mean AUPR values of 0.928 ± 0.013, 0.844 ± 0.039, and 0.916 ± 0.021, respectively. The postprocessed image was rendered at a full high-definition resolution of 1920 × 1080 pixels at 38.77 ± 1.52 FPS when attached to a surgical visualization system, reaching up to 87.44 ± 3.8 FPS. CONCLUSIONS: Neural Networks can localize, classify, and segment tissues and instruments during VR procedures in real time. We propose a framework for developing surgical guidance and assessment platform that may guide surgical decision-making and help in formulating tools for systematic analyses of VR surgery. Potential applications include collision avoidance to prevent unintended instrument-tissue interactions and the extraction of spatial localization and movement of surgical instruments for surgical data science research. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A Vaccine Targeting Ovine Herpesvirus 2 Glycoprotein B Protects against Sheep-Associated Malignant Catarrhal Fever.

Malignant catarrhal fever (MCF) is a complex and often fatal disease of ungulates. Effective vaccines are needed to avoid MCF outbreaks and mitigate losses. This study aimed to evaluate a sheep-associated MCF (SA-MCF) vaccine candidate targeting ovine herpesvirus 2 (OvHV-2) glycoprotein B (gB). Rabbits were used as a laboratory animal model to test the safety, immunogenicity, and protective efficacy of a chimeric virus consisting of a recombinant, non-pathogenic strain of alcelaphine herpesvirus-1 encoding OvHV-2 ORF8 to express gB (AlHV-1∆ORF73/OvHV-2-ORF8). Viral-vectored immunizations were performed by using the AlHV-1∆ORF73/OvHV-2-ORF8 chimera alone or as a DNA prime (OvHV-2-ORF8)-virus boost regimen. The viral vector was inoculated by intravenous or intramuscular routes and the DNA was delivered by intradermal shots using a gene gun. The vaccine candidates were deemed safe as no clinical signs were observed following any of the immunizations. Anti-OvHV-2 gB antibodies with neutralizing activity were induced by all immunogens. At three weeks post-final immunization, all animals were challenged intranasally with a lethal dose of OvHV-2. MCF protection rates ranging from 66.7% to 71.4% were observed in vaccinated rabbits, while all mock-vaccinated animals developed the disease. The significant protective efficacy obtained with the vaccine platforms tested in this study encourages further trials in relevant livestock species, such as cattle and bison.

Spontaneous lens resorption in a patient with Marshall-Stickler Syndrome and glaucoma.

PURPOSE: The purpose of this case report is to describe the increased fragility of anterior capsule in patients with the rare genetic disease Marshall-Stickler syndrome. OBSERVATIONS: We describe a 3-year old patient with Marshall-Stickler Syndrome and congenital glaucoma treated with glaucoma drainage implant placement who subsequently developed spontaneous lens resorption in one eye, which was noted incidentally during one follow-up appointment. CONCLUSIONS AND IMPORTANCE: It is hypothesized that the lens material left the eye through the glaucoma drainage implant over time. This process was not associated with elevation of intraocular pressures or inflammation and did not require subsequent surgery to remove any residual lens fragments, which has not been reported before to the best of the authors' knowledge.

Evaluation of Artificial Intelligence-Based Intraoperative Guidance Tools for Phacoemulsification Cataract Surgery.

IMPORTANCE: Complications that arise from phacoemulsification procedures can lead to worse visual outcomes. Real-time image processing with artificial intelligence tools can extract data to deliver surgical guidance, potentially enhancing the surgical environment. OBJECTIVE: To evaluate the ability of a deep neural network to track the pupil, identify the surgical phase, and activate specific computer vision tools to aid the surgeon during phacoemulsification cataract surgery by providing visual feedback in real time. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated deidentified surgical videos of phacoemulsification cataract operations performed by faculty and trainee surgeons in a university-based ophthalmology department between July 1, 2020, and January 1, 2021, in a population-based cohort of patients. EXPOSURES: A region-based convolutional neural network was used to receive frames from the video source and, in real time, locate the pupil and in parallel identify the surgical phase being performed. Computer vision-based algorithms were applied according to the phase identified, providing visual feedback to the surgeon. MAIN OUTCOMES AND MEASURES: Outcomes were area under the receiver operator characteristic curve and area under the precision-recall curve for surgical phase classification and Dice score (harmonic mean of the precision and recall [sensitivity]) for detection of the pupil boundary. Network performance was assessed as video output in frames per second. A usability survey was administered to volunteer cataract surgeons previously unfamiliar with the platform. RESULTS: The region-based convolutional neural network model achieved area under the receiver operating characteristic curve values of 0.996 for capsulorhexis, 0.972 for phacoemulsification, 0.997 for cortex removal, and 0.880 for idle phase recognition. The final algorithm reached a Dice score of 90.23% for pupil segmentation and a mean (SD) processing speed of 97 (34) frames per second. Among the 11 cataract surgeons surveyed, 8 (72%) were mostly or extremely likely to use the current platform during surgery for complex cataract. CONCLUSIONS AND RELEVANCE: A computer vision approach using deep neural networks was able to pupil track, identify the surgical phase being executed, and activate surgical guidance tools. These results suggest that an artificial intelligence-based surgical guidance platform has the potential to enhance the surgeon experience in phacoemulsification cataract surgery. This proof-of-concept investigation suggests that a pipeline from a surgical microscope could be integrated with neural networks and computer vision tools to provide surgical guidance in real time.

Digital Education in Ophthalmology.

ABSTRACT: Accessibility to the Internet and computer systems has prompted the gravitation towards digital learning in medicine, including ophthalmology. Using the PubMed database and Google search engine, current initiatives in ophthalmology that serve as alternatives to traditional in-person learning with the purpose of enhancing clinical and surgical training were reviewed. This includes the development of teleeducation modules, construction of libraries of clinical and surgical videos, conduction of didactics via video communication, and the implementation of simulators and intelligent tutoring systems into clinical and surgical training programs. In this age of digital communication, teleophthalmology programs, virtual ophthalmological society meetings, and online examinations have become necessary for conducting clinical work and educational training in ophthalmology, especially in light of recent global events that have prevented large gatherings as well as the rural location of various populations. Looking forward, web-based modules and resources, artificial intelligence-based systems, and telemedicine programs will augment current curricula for ophthalmology trainees.

POSTERIOR TRACTIONAL MEMBRANES FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINOPATHY OF PREMATURITY.

PURPOSE: To report two cases of tractional membrane formation following treatment with anti-vascular endothelial growth factor therapy in infants with Stage-3 retinopathy of prematurity. METHODS: Retrospective review of electronic medical record for historical information, clinical examination documentation, and imaging from fundus photography, retinal ultrasonography, and fluorescein angiography. RESULTS: Two patients with Stage-3 retinopathy of prematurity, previously treated with laser therapy and intravitreal bevacizumab, were referred to our institution for tractional membranes. The first case is of a male infant with Zone-II disease that progressed to Stage 4A with evidence of inferotemporal tractional retinal detachment only in the left eye. The second case is of a male infant with stable Zone-I disease with an epiretinal membrane in the left eye.Pars plicata vitrectomy and membranectomy were required for both cases because of the concern for subsequent tractional retinal detachment. CONCLUSION: Formation of tractional retinal membranes has been associated with anti-vascular endothelial growth factor therapy. These cases describe the formation of posterior tractional membranes after anti-vascular endothelial growth factor therapy. This potential ocular outcome should be considered when determining treatment plans for retinopathy of prematurity.

Assessment and management of retinopathy of prematurity in the era of anti-vascular endothelial growth factor (VEGF).

The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and improve ROP awareness. Advancements in imaging techniques, expansion of telemedicine services, and the potential for artificial intelligence-assisted ROP screening programs have created opportunities to improve ROP care in areas with a shortage of ophthalmologists trained in ROP. To address the gap in provider knowledge regarding ROP, the Global Education Network for Retinopathy of Prematurity (GEN-ROP) created a web-based tele-education training module that can be used to educate all providers involved in ROP, including non-physician ROP screeners. Over the past 50 years, the treatment of severe ROP has evolved from limited treatment modalities to cryotherapy and laser photocoagulation. More recently, there has been growing evidence to support the use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of severe ROP. However, VEGF is known to be important in organogenesis and microvascular maintenance, and given that intravitreal anti-VEGF treatment can result in systemic VEGF suppression over a period of at least 1-12 weeks, there are concerns regarding adverse effects and long-term ocular and systemic developmental consequences of anti-VEGF therapy. Future research in ophthalmology to address the growing burden of ROP should focus on cost-effective fundus imaging devices, implementation of artificial intelligence platforms, updated treatment algorithms with optimal use of anti-VEGF and careful investigation of its long-term effects, and surgical options in advanced ROP. Addressing these unmet needs will aid the global effort against the ROP epidemic and optimize our understanding and treatment of this blinding disease.

Addressing the Third Epidemic of Retinopathy of Prematurity Through Telemedicine and Technology: A Systematic Review.

The rising prevalence of retinopathy of prematurity (ROP) in low- and middle-income countries has increased the need for screening at-risk infants. The purpose of this article was to review the impact of tele-medicine and technology on ROP screening programs. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed using PubMed, Pro-Quest, and Google Scholar bibliographic search engine. Terms searched included retinopathy of prematurity, telemedicine, and tele-ophthalmology. Data regarding internet access and gross domestic product per capita were obtained from the World Bank. Information was also obtained about internet access, speeds, and costs in low-income countries. There has been increasing integration of telemedicine and technology for ROP screening and management. Low-income countries are using available internet options and information and communications technology for ROP screening, which can aid in addressing the unique challenges faced by low-income countries. This provides a promising solution to the third epidemic of ROP by expanding and improving screening and management. Although telemedicine systems may serve as a cost-effective approach to facilitate delivery of health care, programs (especially in lowand middle-income countries) require national support to maintain its infrastructure. [J Pediatr Ophthalmol Strabismus. 2021;58(4):261-269.].

Evaluation of pediatric ophthalmologists' perspectives of artificial intelligence in ophthalmology.

PURPOSE: To survey pediatric ophthalmologists on their perspectives of artificial intelligence (AI) in ophthalmology. METHODS: This is a subgroup analysis of a study previously reported. In March 2019, members of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) were recruited via the online AAPOS discussion board to voluntarily complete a Web-based survey consisting of 15 items. Survey items assessed the extent participants "agreed" or "disagreed" with statements on the perceived benefits and concerns of AI in ophthalmology. Responses were analyzed using descriptive statistics. RESULTS: A total of 80 pediatric ophthalmologists who are members of AAPOS completed the survey. The mean number of years since graduating residency was 21 years (range, 0-46). Overall, 91% (73/80) reported understanding the concept of AI, 70% (56/80) believed AI will improve the practice of ophthalmology, 68% (54/80) reported willingness to incorporate AI into their clinical practice, 65% (52/80) did not believe AI will replace physicians, and 71% (57/80) believed AI should be incorporated into medical school and residency curricula. However, 15% (12/80) were concerned that AI will replace physicians, 26% (21/80) believed AI will harm the patient-physician relationship, and 46% (37/80) reported concern over the diagnostic accuracy of AI. CONCLUSIONS: Most pediatric ophthalmologists in this survey viewed the role of AI in ophthalmology positively.

Impact of Artificial Intelligence on Medical Education in Ophthalmology.

Clinical care in ophthalmology is rapidly evolving as artificial intelligence (AI) algorithms are being developed. The medical community and national and federal regulatory bodies are recognizing the importance of adapting to AI. However, there is a gap in physicians' understanding of AI and its implications regarding its potential use in clinical care, and there are limited resources and established programs focused on AI and medical education in ophthalmology. Physicians are essential in the application of AI in a clinical context. An AI curriculum in ophthalmology can help provide physicians with a fund of knowledge and skills to integrate AI into their practice. In this paper, we provide general recommendations for an AI curriculum for medical students, residents, and fellows in ophthalmology.

OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model.

An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine strain. Alternative approaches for vaccine development are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9% of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the mock-vaccinated group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards an SA-MCF vaccine; however, improvements are needed to increase protection rates.