The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs.

BACKGROUND: Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody-associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss. It is important to distinguish MS ON from other ON subtypes early, to guide appropriate management. Yet, identifying ON and differentiating subtypes can be challenging as MRI and serological antibody test results are not always readily available in the acute setting. The purpose of this study is to develop a deep learning artificial intelligence (AI) algorithm to predict subtype based on fundus photographs, to aid the diagnostic evaluation of patients with suspected ON. METHODS: This was a retrospective study of patients with ON seen at our institution between 2007 and 2022. Fundus photographs (1,599) were retrospectively collected from a total of 321 patients classified into 2 groups: MS ON (262 patients; 1,114 photographs) and non-MS ON (59 patients; 485 photographs). The dataset was divided into training and holdout test sets with an 80%/20% ratio, using stratified sampling to ensure equal representation of MS ON and non-MS ON patients in both sets. Model hyperparameters were tuned using 5-fold cross-validation on the training dataset. The overall performance and generalizability of the model was subsequently evaluated on the holdout test set. RESULTS: The receiver operating characteristic (ROC) curve for the developed model, evaluated on the holdout test dataset, yielded an area under the ROC curve of 0.83 (95% confidence interval [CI], 0.72-0.92). The model attained an accuracy of 76.2% (95% CI, 68.4-83.1), a sensitivity of 74.2% (95% CI, 55.9-87.4) and a specificity of 76.9% (95% CI, 67.6-85.0) in classifying images as non-MS-related ON. CONCLUSION: This study provides preliminary evidence supporting a role for AI in differentiating non-MS ON subtypes from MS ON. Future work will aim to increase the size of the dataset and explore the role of combining clinical and paraclinical measures to refine deep learning models over time.

Stabilization of refractive error and associated factors following small incision phacoemulsification cataract surgery.

BACKGROUND: Accumulating evidence suggests that refractive stabilization occurs rapidly following small incision cataract surgery. Nonetheless, many guidelines still suggest waiting four to 6 weeks before prescribing corrective lenses. This study was undertaken to supplement the existing literature regarding refractive stabilization, and evaluate multiple contributing factors that could dissuade clinicians from confidently correcting refractive error in the early post-operative course following routine cataract surgeries. METHODS: Adult patients undergoing phacoemulsification cataract surgery with uncomplicated surgeries and post-surgical courses at the Calgary Ophthalmology Centre (Calgary, Alberta, Canada) were included in this prospective observational case series. Exclusion criteria included known corneal dystrophies, infectious keratitis, complicated surgery or toric/multifocal IOLs. Data was collected at weekly intervals for a total of 6 weeks. Collected data included autorefraction, visual acuity, corneal pachymetry, and effective lens position. RESULTS: One hundred six eyes of 104 patients were included in this study. Post-operative sphere, cylinder and spherical equivalent were not significantly different at any post-operative week compared with week six, and 80-86% of patients were within 0.5D of last follow-up spherical equivalent at any week. The secondary outcomes of central corneal thickness, effective lens position and visual acuity did, however, exhibit significant differences between early post-operative weeks and last follow-up values. CONCLUSIONS: These data suggest that refractive error can be effectively measured and corrected as early as one-week post-operatively in the majority of patients, though other measures of post-operative stability including central corneal thickness, effective lens position and visual acuity can require up to 4 weeks to stabilize. Thus a conservative and pragmatic approach may be to wait until 4 weeks post-operatively prior to obtaining refractive correction following uncomplicated phacoemulsification cataract surgery.

Efficacy of gonioscopy-assisted transluminal trabeculotomy in advanced-age glaucoma patients.

BACKGROUND: The prevalence and severity of many etiologies of glaucoma increase with age, often requiring surgery later in life. Surgery in the most aged demographic, however, poses multiple unique physiologic and psychosocial challenges with variable outcomes. In this study, we evaluate the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in an advanced-age population (>85 years of age). METHODS: This is a single-centre retrospective cohort study of consecutive patients who underwent GATT at or above 85 years of age. This included patients with GATT of any circumferential extent (90°-360°) with or without concurrent phacoemulsification cataract surgery. The primary outcome measure was proportion of successful surgeries at 1 year by the "complete success" criteria (intraocular pressure [IOP] <17 mm Hg on no medications 3 months after surgery with no additional interventions). Secondary outcomes included proportion of successful surgeries by alternative criteria, cross-sectional analyses of IOPs and medication use, and analyses of postoperative complications and interventions. RESULTS: Forty eyes of 31 patients were included in the study. Mean baseline IOP was 16.75 ± 7.33 mm Hg on 1.60 ± 1.43 classes of medication. At 1 year, the cumulative survival by Kaplan-Meier analysis was 46.6%. There was a statistically significant reduction in IOP at all postoperative time points to a mean of 11.78 ± 3.07 mm Hg at the last follow-up. There were postoperative complications in 18 eyes, with hyphema and corneal edema accounting for the majority. CONCLUSIONS: This study provides evidence that GATT is a safe and effective intervention in advanced-age glaucoma populations.

Segmental Suture Gonioscopy-Assisted Transluminal Trabeculotomy: Comparison of Superior Versus Inferior Hemisphere Outcomes.

PRCIS: Analysis of efficacy, safety, and risk factors for failure of superior versus inferior 180-degree segmental gonioscopy-assisted transluminal trabeculectomy showed no significant difference between approaches, with novel risk factors for failure identified. PURPOSE: Compare the efficacy, safety, and risk factors for failure of superior versus inferior 180-degree segmental suture gonioscopy-assisted transluminal trabeculotomy (GATT). DESIGN: Multicenter, retrospective interventional cohort study of 297 eyes of 243 glaucomatous patients, which underwent superior or inferior 180-degree suture hemi-GATT surgery combined with phacoemulsification at one of 3 Canadian ophthalmological surgical centres in Calgary, Alberta or Toronto, Ontario. MAIN OUTCOME MEASURES: The primary outcome measure was the hazard ratio (HR) of failure for the "primary success" criteria. "Primary success" was defined as an intraocular pressure (IOP) <18 mm Hg and either 1) IOP reduced by ≥20% from baseline on the same number of IOP-lowering medications or 2) IOP ≤ baseline on fewer medications. Secondary outcome measures included HRs of failure for alternative criteria ("complete success", "qualified success" and "20% IOP reduction"), cross-sectional analysis, and Cox proportional hazard analysis for risk factors associated with increased failure for the complete cohort. RESULTS: Baseline characteristics were similar between groups. The crude and adjusted HR of failure for the "primary success" criteria for superior surgeries relative to inferior surgeries were 1.27 (95% CI = 0.86-1.88) and 1.50 (95% CI = 0.91-2.46), with no statistically significant difference between approaches. Of the secondary criteria, there was statistical significance in favor of inferior surgeries only for crude analysis of the "20% reduction" criteria (1.40/1.27 (95% CI = 1.01-1.92). Increased risk of failure by the "primary success" measure for either intervention was seen with primary open angle glaucoma, advanced disease, and age below 70 years. There were no significant differences in the frequency of postoperative complications between cohorts, which were present in 72 superior (44.4%) and 67 inferior (49.6%; P value = 0.41) eyes; mostly early postoperative hyphema, iritis, and corneal edema. CONCLUSIONS: This retrospective study showed no difference in inferior versus superior 180 degrees of hemi-GATT/phacoemulsification cataract surgeries through the majority of analyses. Nonmodifiable factors including glaucoma type, advanced disease, and younger age were associated with a significantly higher risk of failure in this cohort. Further study is warranted.

Comparison of 3D heads-up display system with conventional surgical microscopy for minimally invasive glaucoma surgery on an artificial eye model.

OBJECTIVE: To survey ophthalmic surgeons' opinions comparing a novel three-dimensional (3D) heads-up display system with a conventional surgical microscopy for minimally invasive glaucoma surgery (MIGS) on an artificial eye model. MATERIALS AND METHODS: Twenty-one ophthalmologists at the 2021 Canadian Ophthalmological Society Annual Meeting in Halifax, Nova Scotia, underwent a 90-minute skills-transfer course on MIGS. Using an artificial eye model (SimulEYE iTrack Model; InsEYE LLC, Westlake Village, Calif.), participants engaged in hands-on practice of MIGS via both a 3D heads-up display system (3D HUDS) (Zeiss Artevo 800; Carl Zeiss Meditec, Jena, Germany) and a conventional surgical microscope. Following completion, participants and instructors answered a 16-question survey comparing the 2 systems (3D HUDS vs conventional surgical microscope). Survey responses were recorded on a 9-point double-headed Likert scale ranging from strongly favour 3D HUDS (1) to strongly favour conventional surgical microscopy (9). Mann-Whitney U nonparametric analysis was used to compare instructor versus participants and experts versus nonexperts. RESULTS: Survey ratings favoured the 3D HUDS over the conventional surgical microscopy, with respondent ratings for all survey questions ranging from a response of 1 (strongly favour 3D HUDS) to 5 (equal). Mann-Whitney U statistical analysis revealed no significant difference between instructor versus participant as well as between expert versus nonexpert. Most ratings for the 3D HUDS were received for ergonomic setup of the surgical modality, depth of field (or) field of view, and usefulness in training residents for MIGS. Equal ratings for the 3D HUDS and conventional surgical microscope were received for system malfunctions and lag during surgery. CONCLUSIONS: The 3D HUDS was favoured over conventional microscopy for the performance of simulated MIGS by ophthalmologists with varying levels of experience. The survey results suggest that the 3D HUDS in an artificial eye model is useful for teaching minimally invasive glaucoma surgery, particularly with the advent of competency-based ophthalmology education programs.

Face and Content Validity of an Artificial Eye Model for Secondary Intraocular Lens Fixation via Yamane Technique.

Purpose: To assess the face and content validity of an artificial eye model for secondary intraocular lens (IOL) fixation via the Yamane technique. Methods: Ophthalmologists and residents participated in a 90-minute simulation session on secondary IOL fixation via the Yamane technique. Hands-on practice of this technique was performed on an artificial eye, the Bioniko Okulo BR8. After, all ophthalmologists answered an 18-question survey assessing the face and content validity of the model. Survey responses were recorded on a 5-point double-headed Likert scale, ranging from strongly agree (1)-to-strongly disagree (5) (Figure 1). Results: Twenty-three surveys were completed. Respondents rated the survey with a median response of 1 (strongly agree)-to-3 (neutral). Highest ratings for the model were received for "usefulness for training residents", and "easier to set up and clean-up compared to a cadaver". Lowest ratings were received for realism of the model compared to cadaveric eyes. Statistical analysis revealed no significant difference among identified groups. Ratings for face and content validity were viewed favorably, both with an overall median response of 2.00 (agree). Conclusion: The Bioniko Okulo BR8 shows promise as a valid tool for practicing secondary IOL fixation via the Yamane technique. Considering recent guidelines in competency-based ophthalmology education programs, this model may be a valuable tool over traditional techniques for teaching and improving surgical skill amongst trainees.

Gonioscopy-assisted transluminal trabeculotomy is an effective surgical treatment for uveitic glaucoma.

BACKGROUND: To assess the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in uveitic glaucoma (UG). METHODS: A retrospective interventional case series in which 33 eyes of 32 patients with UG underwent GATT with or without concomitant cataract extraction and intraocular lens implantation (CE/IOL) at three Canadian treatment centres from October 2015 to 2020. The main outcome measure was surgical success defined as an intraocular pressure (IOP) ≤18 mm Hg and at least one of the following: IOP within one mm Hg of baseline on fewer glaucoma medications as compared with baseline or a 30% IOP reduction from baseline on the same or fewer medications. Secondary outcome measures were IOP, medication usage and surgical complications. RESULTS: Mean patient age (mean±SD) was 49±16 years (range: 18-79) and 44% were female. GATT was performed as a standalone procedure in 52% of cases and the remainder were combined with CE/IOL. Surgical success was achieved in 71.8% (SE: 8.7%) of cases. Mean preoperative IOP (±SD) was 31.4±10.8 mm Hg on a median of 4 medications. 59% of patients were on oral carbonic anhydrase inhibitors (CAIs) prior to surgery. After 1 year, average IOP was 13.8 mm Hg on a median 1 medication, with 6% of patients being on oral CAIs. No sight threatening complications occurred during surgery or follow-up. CONCLUSION: GATT is an effective surgical strategy in the management of UG. This microinvasive conjunctival-sparing procedure should be considered early in these patients.

Face and content validity of an artificial eye model for Ab-Interno Goniotomy.

PURPOSE: To determine the face and content validity of an artificial eye model for ab-interno goniotomy (SimulEYE KDB model, InsEYEt, Westlake Village, CA) by surveying ophthalmologists with varying experience using a Kahook Dual Blade (KDB; New World Medical, Rancho Cucamonga, CA, USA) following a 90-min wet-lab course using the model. PARTICIPANTS: Overall 13 ophthalmologists participated following a surgical simulation session on goniotomy using the goniotomy blade at the 2019 Canadian Ophthalmological Society annual meeting. METHODS: A 17-question survey to assess the face and content validity of the model was given immediately following the surgical simulation session on goniotomy using the goniotomy blade. Responses to each survey question were recorded on a 5-point Likert scale ranging from (1) strongly agree to (5) strongly disagree. RESULTS: Respondents rated statements regarding the model with a median response of 1 (Strongly Agree) to 3 (Neither agree or disagree). Mann-Whitney U nonparametric analysis revealed no significant difference in responses between instructor vs. non-instructor or between prior experience vs. no prior experience for any of the survey statements. The model received highest survey ratings for utility in training residents, acquisition of surgical skills, accessibility, and higher likelihood of success with the procedure than theory and observation alone. Lowest ratings were for realism of the model compared to a human cadaveric eye. CONCLUSION: Our results suggest the SimulEYE KDB model is a reasonably cost-effective solution for simulating angle-based surgeries. Additionally, our project shows that experienced ophthalmologists found the artificial eye models useful and helpful for angle-based surgery training.

Ab Interno Canaloplasty in Open-angle Glaucoma Patients Combined With In Vivo Trypan Blue Aqueous Venography.

PURPOSE: To demonstrate canalogram patterns observed when trypan blue tracer is combined with oculoviscoelastic device during ab interno canaloplasty, and discuss surgical results and potential implications for diagnosis, prognosis, and treatment. METHODS: This is a retrospective small case series study. RESULTS: The authors performed this procedure on 5 patients with informed consent with 4 to 18 months of follow-up. All procedures have been complication free. The average preoperative intraocular pressure was 16.4 mm Hg with an average number of topical glaucoma medications being equal to 3.6. Postoperatively, the average intraocular pressure for the group was reduced to 13 mm Hg with a concurrent drop in the average number of topical medications used equaling 1.8. CONCLUSIONS: Currently, there are limited practical options to evaluate the patency of the aqueous outflow system in our patients. The primary purpose of this paper is to describe canalogram patterns observed during ab interno canaloplasty with trypan blue. This technique may allow us to further our understanding of the aqueous outflow system and its role in the underlying pathophysiology of glaucoma. Further research is required to evaluate the prognostic and diagnostic significance of this technique.

Transgenic Expression of Cacna1f Rescues Vision and Retinal Morphology in a Mouse Model of Congenital Stationary Night Blindness 2A (CSNB2A).

Purpose: Congenital stationary night blindness 2A (CSNB2A) is a genetic retinal disorder characterized by poor visual acuity, nystagmus, strabismus, and other signs of retinal dysfunction resulting from mutations in Cacna1f-the gene coding for the pore-forming subunit of the calcium channel CaV1.4. Mouse models of CSNB2A have shown that mutations causing the disease deleteriously affect photoreceptors and their synapses with second-order neurons. This study was undertaken to evaluate whether transgenic expression of Cacna1f could rescue morphology and visual function in a Cacna1f-KO model of CSNB2A. Methods: Strategic creation, breeding and use of transgenic mouse lines allowed for Cre-driven retina-specific expression of Cacna1f in a CSNB2A model. Transgene expression and retinal morphology were investigated with immunohistochemistry in retinal wholemounts or cross-sections. Visual function was assessed by optokinetic response (OKR) analysis and electroretinography (ERG). Results: Mosaic, prenatal expression of Cacna1f in the otherwise Cacna1f-KO retina was sufficient to rescue some visual function. Immunohistochemical analyses demonstrated wild-type-like photoreceptor and synaptic morphology in sections with transgenic expression of Cacna1f. Conclusions: This report describes a novel system for Cre-inducible expression of Cacna1f in a Cacna1f-KO mouse model of CSNB2A and provides preclinical evidence for the potential use of gene therapy in the treatment of CSNB2A. Translational Relevance: These data have relevance in the treatment of CSNB2A and in understanding how photoreceptor integration might be achieved in retinas in which photoreceptors have been lost, such as retinitis pigmentosa, age-related macular degeneration, and other degenerative conditions.

Avian Adeno-Associated Viral Transduction of the Postembryonic Chicken Retina.

PURPOSE: The posthatching chicken is a valuable animal model for research, but molecular tools needed for altering its gene expression are not yet available. Our purpose here was to adapt the adeno-associated viral (AAV) vector method, used widely in mammalian studies, for use in investigations of the chicken retina. We hypothesized that the recently characterized avian AAV (A3V) vector could effectively transduce chick retinal cells for manipulation of gene expression, after intravitreal or subretinal injection. METHODS: A3V encoding enhanced green fluorescent protein (EGFP) was injected intravitreally or subretinally into P1-3 chick eye and left for 7 to 10 days. Retinas were then sectioned or flat-mounted and visualized via laser-scanning confocal microscopy for analysis of expression and imaging of retinal cells. RESULTS: Intravitreal A3V-EGFP injection resulted in EGFP expression in a small percent of retinal cells, primarily those with processes and/or cell bodies near the vitreal surface. In contrast, subretinal injection of A3V-EGFP within confined retinal "blebs" produced high rates of transduction of rods and all types of cones. Some examples of all other major retinal cell types, including horizontal, amacrine, bipolar, ganglion, and Müller cells, were also transduced, although with much lower frequency than photoreceptors. CONCLUSIONS: A3V is a promising tool for investigating chick retinal cells and circuitry in situ. This novel vector can be used for studies in which local photoreceptor transduction is sufficient for meaningful observations. TRANSLATIONAL RELEVANCE: With this vector, the postembryonic chick retina can now be used for preclinical trials of gene therapy for prevention and treatment of human retinal disease.