APPLICATIONS OF MULTIMODAL GENERATIVE ARTIFICIAL INTELLIGENCE IN A REAL-WORLD RETINA CLINIC SETTING.

PURPOSE: This study evaluates a large language model, Generative Pre-trained Transformer 4 with vision, for diagnosing vitreoretinal diseases in real-world ophthalmology settings. METHODS: A retrospective cross-sectional study at Bascom Palmer Eye Clinic, analyzing patient data from January 2010 to March 2023, assesses Generative Pre-trained Transformer 4 with vision's performance on retinal image analysis and International Classification of Diseases 10th revision coding across 2 patient groups: simpler cases (Group A) and complex cases (Group B) requiring more in-depth analysis. Diagnostic accuracy was assessed through open-ended questions and multiple-choice questions independently verified by three retina specialists. RESULTS: In 256 eyes from 143 patients, Generative Pre-trained Transformer 4-V demonstrated a 13.7% accuracy for open-ended questions and 31.3% for multiple-choice questions, with International Classification of Diseases 10th revision code accuracies at 5.5% and 31.3%, respectively. Accurately diagnosed posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment. International Classification of Diseases 10th revision coding was most accurate for nonexudative age-related macular degeneration, central retinal vein occlusion, and macular hole in OEQs, and for posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment in multiple-choice questions. No significant difference in diagnostic or coding accuracy was found in Groups A and B. CONCLUSION: Generative Pre-trained Transformer 4 with vision has potential in clinical care and record keeping, particularly with standardized questions. Its effectiveness in open-ended scenarios is limited, indicating a significant limitation in providing complex medical advice.

PPP3CA truncating variants clustered in the regulatory domain cause early-onset refractory epilepsy.

PPP3CA encodes the catalytic subunit of calcineurin, a calcium-calmodulin-regulated serine-threonine phosphatase. Loss-of-function (LoF) variants in the catalytic domain have been associated with epilepsy, while gain-of-function (GoF) variants in the auto-inhibitory domain cause multiple congenital abnormalities. We herein report five new patients with de novo PPP3CA variants. Interestingly, the two frameshift variants in this study and the six truncating variants reported previously are all located within a 26-amino acid region in the regulatory domain (RD). Patients with a truncating variant had more severe earlier onset seizures compared to patients with a LoF missense variant, while autism spectrum disorder was a more frequent feature in the latter. Expression studies of a truncating variant showed apparent RNA expression from the mutant allele, but no detectable mutant protein. Our data suggest that PPP3CA truncating variants clustered in the RD, causing more severe early-onset refractory epilepsy and representing a type of variants distinct from LoF or GoF missense variants.

POU6f1 Mediates Neuropeptide-Dependent Plasticity in the Adult Brain.

The mouse olfactory bulb (OB) features continued, activity-dependent integration of adult-born neurons, providing a robust model with which to examine mechanisms of plasticity in the adult brain. We previously reported that local OB interneurons secrete the neuropeptide corticotropin-releasing hormone (CRH) in an activity-dependent manner onto adult-born granule neurons and that local CRH signaling promotes expression of synaptic machinery in the bulb. This effect is mediated via activation of the CRH receptor 1 (CRHR1), which is developmentally regulated during adult-born neuron maturation. CRHR1 is a GS-protein-coupled receptor that activates CREB-dependent transcription in the presence of CRH. Therefore, we hypothesized that locally secreted CRH activates CRHR1 to initiate circuit plasticity programs. To identify such programs, we profiled gene expression changes associated with CRHR1 activity in adult-born neurons of the OB. Here, we show that CRHR1 activity influences expression of the brain-specific Homeobox-containing transcription factor POU Class 6 Homeobox 1 (POU6f1). To elucidate the contributions of POU6f1 toward activity-dependent circuit remodeling, we targeted CRHR1+ neurons in male and female mice for cell-type-specific manipulation of POU6f1 expression. Whereas loss of POU6f1 in CRHR1+ neurons resulted in reduced dendritic complexity and decreased synaptic connectivity, overexpression of POU6f1 in CRHR1+ neurons promoted dendritic outgrowth and branching and influenced synaptic function. Together, these findings suggest that the transcriptional program directed by POU6f1 downstream of local CRH signaling in adult-born neurons influences circuit dynamics in response to activity-dependent peptide signaling in the adult brain.SIGNIFICANCE STATEMENT Elucidating mechanisms of plasticity in the adult brain is helpful for devising strategies to understand and treat neurodegeneration. Circuit plasticity in the adult mouse olfactory bulb is exemplified by both continued cell integration and synaptogenesis. We previously reported that these processes are influenced by local neuropeptide signaling in an activity-dependent manner. Here, we show that local corticotropin-releasing hormone (CRH) signaling induces dynamic gene expression changes in CRH receptor expressing adult-born neurons, including altered expression of the transcription factor POU6f1 We further show that POU6f1 is necessary for proper dendrite specification and patterning, as well as synapse development and function in adult-born neurons. Together, these findings reveal a novel mechanism by which peptide signaling modulates adult brain circuit plasticity.

Can Google Help Your Nearsightedness? A Google Trend Analysis of Public Interest in Myopic Progression.

Purpose: To explore public interest in myopia progression and management and to correlate these trends to available treatments. Methods: Keywords were chosen for interest in myopia overall and those signifying interest in myopia treatments. Treatment options were separated into four main categories: atropine, glasses, contact lenses, and orthokeratology. Search terms were queried across ten years of Google Trends data and the relative search volume was analyzed to quantify the change in search volume over time. Results: A positive linear trend over time was present for all myopia interest keywords except "nearsighted" (p = 0.074) and "near work myopia" (p = 0.086). Interest in the four myopia treatment categories included in this study also displayed a significant positive trend over time. There is also a statistically significant positive correlation between all four treatment options and four of the seven categories of population interest, "myopia control", "myopia", "myopia progression", and "screen time myopia". Conclusion: This study demonstrates the utility of GT to correlate public interest in myopia treatments over time. All treatment terms had statistically significant linear search volume growth over a ten-year period. The positive correlation between interest in myopia as a health problem and available treatments supports existing evidence that GT can track rising public health concerns and corresponding treatment-seeking behaviors.

A novel case of Horner syndrome as the presenting sign of craniosynostosis.

Craniosynostosis, the premature fusion of cranial sutures, can lead to distortion of skull shape and neurological dysfunction. We present a novel case of Horner syndrome as the presenting sign of craniosynostosis associated with elevated intracranial pressure. A 10-year-old boy presenting for strabismus follow-up was noted to have new-onset anisocoria, greater in the dark, and mild right upper eyelid ptosis. Apraclonidine testing was concerning for Horner syndrome. Neuroimaging demonstrated previously undiagnosed sagittal craniosynostosis with tortuous optic nerves and large cerebrospinal fluid spaces around both optic nerves. The patient was referred to neurosurgery and underwent a lumbar puncture with an opening pressure of 44 cm H2O. He underwent surgical cranial expansion. By six months postoperatively, his anisocoria had resolved.

Spontaneous collapse of an iris stromal cyst in a young child.

A 4-month-old girl was referred for evaluation of an anterior chamber cyst in the left eye. Examination under anesthesia (EUA) revealed a large iris stromal cyst in the anterior chamber involving the angle and the pupillary border, with touch of the corneal endothelium and anterior lens capsule. Intraocular pressure was normal. There was no anisometropic refractive error by retinoscopy. Close observation with amblyopia management was recommended as the pupil was only partially occluded by the cyst, and there was a clear red reflex around the cyst. Repeat EUA 6 months following diagnosis showed spontaneous collapse of the cyst. There was no recurrence noted at her most recent follow-up, 2 years after presentation, and most of the pupillary axis remains unobstructed by the cyst. The patient continues to be followed to monitor for possible cyst progression, anisometropia, and development of amblyopia. Though rare, spontaneous resolution of an iris stromal cyst may occur and thus, observation may be considered, particularly if the cyst is not causing anterior segment complications or obstruction of the visual axis.

Efficacy and Safety of Anti-VEGF Injections and Surgery for Age-Related Macular Degeneration-Related Submacular Hemorrhage: A Systematic Review and Meta-Analysis.

TOPIC: This systematic review and meta-analysis investigates the efficacy and safety of anti-VEGF injections compared with surgical intervention in improving visual acuity (VA) and reducing complications for patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD). CLINICAL RELEVANCE: Determining the optimal intervention for SMH in AMD is crucial for patient care. METHODS: We included studies on anti-VEGF injections or surgical interventions for SMH in AMD from 7 databases, searched up to May 2024. Data extraction and quality assessment were done by 2 independent reviewers. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis employed random-effects models. Primary outcomes were pooled mean logarithm of the minimum angle of resolution VA difference (initial examination minus last follow-up VA) and adverse events rates. RESULTS: A total of 43 observational studies were included: 21 (960 eyes) on anti-VEGF and 22 (455 eyes) on surgery. Comparisons were made across separate studies due to lack of head-to-head studies. Meta-analysis included 11 anti-VEGF studies (444 eyes) and 12 surgical studies (195 eyes) for VA outcomes. The mean difference in VA was -0.16 (95% confidence interval (CI), -0.24 to -0.08) for anti-VEGF and -0.36 (95% CI, -0.68 to -0.04) for surgery, with no significant difference between groups (chi-square = 1.70, df = 1, P = 0.19). Heterogeneity was high in surgical studies (I2 = 96.2%, τ2 = 0.23, P < 0.01) and negligible in anti-VEGF studies (I2 = 7%, τ2 = 0.003, P = 0.38). The GRADE certainty was moderate for anti-VEGF and low for surgery. Anti-VEGF had lower rates of cataract (0% vs. 4.6%), proliferative vitreoretinopathy (0.1% vs. 2.0%), and retinal detachment (0.1% vs. 10.6%), but similar rates of recurrent hemorrhage (5.4% vs. 5.3%). Complications were summarized descriptively due to zero-cell problem. CONCLUSION: Both anti-VEGF and surgery treat SMH in AMD with similar VA outcomes but different safety profiles. Anti-VEGF is preferred for less severe hemorrhage, whereas surgery is suited for extensive hemorrhage. Despite uncertain comparative VA outcomes, treatment should be guided by clinical judgment and patient factors. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Proliferative Sickle Cell Retinopathy: Outcomes of Vitreoretinal Surgery.

PURPOSE: To report the clinical presentation and outcomes in patients who underwent surgery for proliferative sickle cell retinopathy (PSCR). DESIGN: Retrospective, consecutive case series. SUBJECTS: All patients who underwent vitreoretinal surgery for complications secondary to PSCR between January 1, 2014, and December 31, 2021, at a university referral center. METHODS: Retrospective consecutive case series. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), single operation anatomic success rate. RESULTS: The study included 65 eyes of 61 patients. Disease distribution included 24 (44.4%) eyes with hemoglobin SC disease, 14 (25.9%) with hemoglobin SS disease, 13 (24.1%) with sickle cell trait, and 3 (5.6%) with sickle cell-ß thalassemia. Preoperative transfusion was not performed in any study patients. Regional anesthesia with monitored anesthesia care (RA-MAC) was utilized in 58 (89.2%) eyes and general anesthesia in 7 (10.8%). In eyes that underwent surgery for retinal detachment (RD; N = 52) the rate of single operation anatomic success was 72.4% with combined scleral buckling/pars plana vitrectomy (SB/PPV; N = 29) compared with 47.8% with PPV alone (N = 23; P = 0.07). Mean BCVA at the last follow-up examination was 1.27 (20/372) in the SB/PPV group and 1.05 (20/226) in the PPV group (P = 0.48). In all SB cases, an encircling band was utilized and there were no known cases of anterior segment ischemia. All eyes that had surgery for vitreous hemorrhage (N = 13) underwent PPV with endolaser and mean BCVA improved from 1.67 (20/944) preoperatively to 0.45 (20/56) at last follow-up examination (P < 0.001). Mean preoperative BCVA, indication for surgery, single operation success rate, and mean BCVA at last follow-up examination did not differ based on sickle cell disease type (P > 0.05). CONCLUSIONS: In patients with RD, SB/PPV achieved slightly higher rates of single operation anatomic success compared with PPV alone. Visual acuity outcomes were similar in the 2 groups. The majority of patients received RA-MAC anesthesia and preoperative transfusions were not performed. There were no cases of postoperative anterior segment ischemia. Hemoglobin SC disease was the most common disease type in the current study and surgical outcomes did not differ between sickle cell disease types. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Olfactory Cued Learning Paradigm.

Sensory stimulation leads to structural changes within the CNS (Central Nervous System), thus providing the fundamental mechanism for learning and memory. The olfactory circuit offers a unique model for studying experience-dependent plasticity, partly due to a continuous supply of integrating adult born neurons. Our lab has recently implemented an olfactory cued learning paradigm in which specific odor pairs are coupled to either a reward or punishment to study downstream circuit changes. The following protocol outlines the basic set up for our learning paradigm. Here, we describe the equipment setup, programming of software, and method of behavioral training.