Faculty Bibliography

BACKGROUND/AIMS/OBJECTIVE:To assess the cost-effectiveness of making treatment decisions for patients with ocular hypertension (OHT) based on a risk prediction (RP) tool in the United Kingdom. METHODS:A discrete event simulation model was constructed to compare the cost-effectiveness of an alternative care pathway in which the treatment decision was guided by a validated RP tool in secondary care against decision-making based on the standard care (SC). Individual patient sampling was used. Patients diagnosed with OHT and with an intraocular pressure of 24 mm Hg or over entered the model with a set of predefined individual characteristics related to their risk of conversion to glaucoma. These characteristics were retrieved from electronic medical records (n=5740). Different stages of glaucoma were modelled following conversion to glaucoma. RESULTS:Almost all (99%) patients were treated using the RP strategy, and less than half (47%) of the patients were treated using the SC strategy. The RP strategy produced higher cost but also higher quality-adjusted life years (QALYs) than the SC strategy. The RP strategy was cost-effective compared with the SC strategy in the base-case analysis, with an incremental cost-effectiveness ratio value of £11 522. The RP strategy had a 96% probability of being cost-effective under a £20 000 per QALY threshold. CONCLUSIONS:The use of an RP tool for the management of patients with OHT is likely to be cost-effective. However, the generalisability of the result might be limited due to the high-risk nature of this cohort and the specific RP threshold used in the study.

While visual responses to familiar and novel stimuli have been extensively studied, it is unknown how neuronal representations of familiar stimuli are affected when they are interleaved with novel images. We examined a large-scale dataset from mice performing a visual go/no-go change detection task. After training with eight images, six novel images were interleaved with two familiar ones. Unexpectedly, we found that the behavioral performance in response to familiar images was impaired when they were mixed with novel images. When familiar images were interleaved with novel ones, the dimensionality of their representation increased, indicating a perturbation of their neuronal responses. Furthermore, responses to familiar images in the primary visual cortex were less predictive of responses in higher-order areas, indicating less efficient communication. Spontaneous correlations between neurons were predictive of responses to novel images, but less so to familiar ones. Our study demonstrates the modification of representations of familiar images by novelty.

BACKGROUND:Continuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period. METHODS:) with 32 directions/shell, providing measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axonal water fraction (AWF), and the permeability-diffusivity index (PDI). RESULTS:Significant reductions (p < 0.05) in the latency and IL of fVEP measurements paralleled significant rises in FA, KA, AWF and PDI over the same period. The longitudinal latency changes in fVEPs were primarily associated with whole-brain changes in diffusion parameters, while fVEP IL changes were related to maturation of the corpus callosum. CONCLUSIONS:Good agreement between reduction in the latency of fVEPs and maturation of cerebral WM was interpreted as evidence for ongoing myelination and confirmation of the minipig as a viable research platform. Adolescent development in minipigs can be studied using human neuroimaging and neurophysiological protocols and followed up with more invasive assays to investigate key neurodevelopmental hypotheses in psychiatry.

The pachychoroid disease spectrum is a phenotype characterized by alterations in choroidal vasculature which result in outer retinal and choriocapillaris damage and visual loss. The presence of pachyvessels is one of the key features of the pachychoroid phenotype. Recent imaging studies suggest that pachyvessels may form because of choroidal venous congestion in one or more quadrants. The formation of intervortex anastomosis may function as a compensatory mechanism to dissipate the increased venous pressure, while outflow obstruction has been hypothesized to occur at the site of the vortex vein exiting the sclera. This review aims to summarize recent imaging findings and discuss evolution in the understanding of pathogenesis of the pachychoroid disease spectrum. We have summarized notable treatment trials in central serous chorioretinopathy and polypoidal choroidal vasculopathy and included an update of the current diagnostic and management strategies of the entities that are part of the pachychoroid disease spectrum.

IMPORTANCE/UNASSIGNED:Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications. OBJECTIVE/UNASSIGNED:To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022. INTERVENTIONS/UNASSIGNED:Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks. MAIN OUTCOMES AND MEASURES/UNASSIGNED:IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection. RESULTS/UNASSIGNED:Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.

IMPORTANCE/UNASSIGNED:The involvement of chronic inflammation in the pathogenesis of age-related macular degeneration (AMD) opens therapeutic possibilities to AMD management. OBJECTIVE/UNASSIGNED:To determine whether Janus kinase inhibitors (JAKis) are associated with a reduced risk of AMD development in patients with autoimmune diseases. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective observational cohort study used administrative claims data from Merative MarketScan research databases (Commercial and Medicare Supplemental) and Optum Clinformatics Data Mart databases between January 1, 2010, and January 31, 2022. Patients with autoimmune diseases satisfying study eligibility criteria and who received JAKi treatment (9126 in MarketScan and 5667 in Optum) were propensity score matched (1:1) to identical numbers of study-eligible patients who received non-JAKi-based immunotherapy. EXPOSURE/UNASSIGNED:Treatment duration of 6 months or longer. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Incidence rates of AMD (exudative and nonexudative) over the first 6 to 18 months of treatment were determined, and bayesian Poisson regression models were used to estimate incidence rate ratios, 95% CIs, and posterior probabilities of AMD. RESULTS/UNASSIGNED:After matching, female sex represented the majority of the patient population in both MarketScan and Optum (14 019/18 252 [76.6%] and 8563/3364 [75.2%], respectively in the JAKi patient population). More than 60% of the patient population was older than 55 years of age in both cohorts. Over the specified treatment period, a 49% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (10/9126 events; adjusted incidence rate ratio [AIRR], 0.51; 95% CI, 0.19-0.90) vs those who received non-JAKi therapy (43/9126 events; AIRR, 1 [reference]) in MarketScan, and a 73% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (3/5667 events; AIRR, 0.27; 95% CI, 0.03-0.74) vs those who received non-JAKi therapy (21/5667 events; AIRR, 1 [reference]) in Optum. The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), favoring patients who received JAKi therapy. Posterior probabilities of the adjusted risk being less than unity were 97.6% (MarketScan) and 98.9% (Optum) for those who received JAKi therapy vs those who received non-JAKi therapy in MarketScan and Optum, respectively. CONCLUSIONS AND RELEVANCE/UNASSIGNED:JAKi use may be associated with a reduced risk of incident AMD in US adults with major autoimmune diseases. The absolute percentage reduction is consistent with a potential role for JAKi in this population. Future studies with long-term follow-up are recommended to investigate the association between JAKi use and incident AMD in other disease indications. Investigation into the role of systemic inflammation and JAK-signal transducers and activators of transcription signaling in AMD may improve understanding of the pathophysiology of AMD and lead to new treatment options.

PURPOSE/OBJECTIVE:To review all cases of Erdheim-Chester disease (ECD) with orbital involvement treated at Bascom Palmer Eye Institute in Miami, Florida from 2014 to 2022 and compare presentations, treatment modalities, and outcomes. METHODS:A retrospective chart review of all patients diagnosed with ECD who presented to Bascom Palmer Eye Institute from 2014 to 2022 was performed. Data collected included demographics, pretreatment history and ophthalmic examination, pathology report, treatment, subsequent examination, and relevant laboratory results. Histopathology, treatments, and outcomes were reviewed and compared between patients. RESULTS:Four cases were included. Primary treatments included vemurafenib (n = 2), cobimetinib (n = 1), and prednisone (n = 1). All patients demonstrated improvement of ophthalmic symptoms. Vemurafenib was the only medical treatment that was tolerated well and resulted in significant improvement in proptosis despite some reported dry eye; all other medications were discontinued due to intolerable side effects. CONCLUSIONS:BRAF inhibitors such as vemurafenib have been used as novel therapy in the treatment of ECD. Vemurafenib demonstrated its utility in reducing proptosis in ECD patients at one ophthalmic institution. Vemurafenib may be a favorable treatment option for BRAF -positive ECD patients presenting with orbital disease.

PURPOSE/OBJECTIVE:Enface OCT may disclose a distinct "fingerprint-like' pattern within the HFL in various macular disorders. This study aims to investigate the frequency and characteristics of this pattern in healthy eyes and identify potential factors influencing its visibility. METHODS:Two, independent masked reading center graders evaluated for the presence and prominence of a fingerprint pattern in the Henle fiber layer (HFL) on enface OCT images from 33 healthy subjects (66 eyes). The prominence of the pattern was rated qualitatively using a 0-3 scale, with 3 indicating the strongest prominence. Tilt angles (relative to the normal/perpendicular at the center) of the retina were measured on horizontal and vertical B-scans, and the retinal curvature was assessed using ImageJ, in order to determine the impact of the incident light angle on the visibility and prominence of the fingerprint pattern. Inter-grader agreement using Cohen's kappa and the frequency and percentage of patterns in the entire enface image and in each quadrant were calculated and compared using the Friedman test with Dunn's post-test. A generalized estimating equation (GEE) was used to analyze the association between these metrics and fingerprint prominence. RESULTS:Substantial inter-grader agreement was observed (Cohen's kappa = 0.71) for assessing the prominence of the fingerprint pattern. Over 70% of eyes exhibited some evidence of the pattern (score ≥1). Significant difference in pattern prominence across quadrants was detected (p < 0.05), with lowest prominence in the temporal quadrant (p < 0.001 for pairwise comparisons against all other quadrants). The GEE analysis to account for the extent of the effect of scan tilt angle and RPE curvature was not able to predict the prominence of the fingerprint pattern, highlighting that angle of incidence (of the scanning laser light) alone could not explain the pattern. CONCLUSIONS:This study confirms that a fingerprint-like pattern within the HFL can also be observed in healthy eyes, challenging the notion that this finding is only manifest in the setting of disease. In addition, the lack of correlation with angle of incident light suggests that the pattern may be related to other intrinsic characteristics of the HFL.

PURPOSE/OBJECTIVE:To determine whether dropless, injection-based cataract surgery prophylaxis with intracameral antibiotic and subconjunctival steroid may reduce healthcare system costs and patient out-of-pocket costs compared to topical medication regimens. SETTING/METHODS:United States national medical expenditures database. DESIGN/METHODS:Retrospective cost analysis. METHODS:Costs were analyzed for topical ophthalmics from the 2020 Medical Expenditure Panel Survey (MEPS) and for dropless medications from pharmaceutical invoices/catalogs. Main outcomes included system costs, from insurance and patient payments, and out-of-pocket costs for cataract surgery topical and dropless, injection-based prophylactic medication regimens, per eye and nationally. System costs for individual topical medications and same-class dropless, injection-based medications were compared using two-sided, one-sample t-tests. RESULTS:There were 583 prophylactic topical ophthalmic purchases in MEPS. Mean system costs per eye were $76.20 ± SD 39.07 for the lowest cost topical steroid (prednisolone) compared to $4.01 for the lowest cost subconjunctival steroid (triamcinolone acetonide) (p < 0.001). Per eye, the lowest cost dropless, injection-based regimen, at $15.91, results in an $87.99 (84.7%) reduction in overall healthcare costs and a $43.64 (100%) reduction in patient out-of-pocket costs relative to the lowest cost topical regimen ($103.90 ± 43.14 mean system cost and $43.64 ± 37.32 mean out-of-pocket cost per eye). Use of intracameral moxifloxacin and subconjunctival triamcinolone acetonide can reduce annual national healthcare system and out-of-pocket costs up to $450,000,000 and $225,000,000, respectively. CONCLUSIONS:An evidence-based cataract surgery prophylactic medication regimen of intracameral moxifloxacin and subconjunctival triamcinolone acetonide can reduce healthcare system and patient out-of-pocket costs in comparison to various topical regimens.