Sequence learning effects in simple perceptual and motor tasks are largely unaffected by normal aging. However, less is known about sequence learning in more complex cognitive tasks that involve attention and memory processes and how this changes with age. In this study, we examined whether incidental and intentional sequence learning would facilitate hybrid visual and memory search in younger and older adults. Observers performed a hybrid search task, in which they memorized four or 16 target objects and searched for any of those target objects in displays with four or 16 objects. The memorized targets appeared either in a repeating sequential order or in random order. In the first experiment, observers were not told about the sequence before the experiment. Only a subset of younger adults and none of the older adults incidentally learned the sequence. The "learners" acquired explicit knowledge about the sequence and searched faster in the sequence compared to random condition. In the second experiment, observers were told about the sequence before the search task. Both younger and older adults searched faster in sequence blocks than random blocks. Older adults, however, showed this sequence-learning effect only in blocks with smaller target sets. Our findings indicate that explicit sequence knowledge can facilitate hybrid search, as it allows observers to predict the next target and restrict their visual and memory search. In older age, the sequence-learning effect is constrained by load, presumably due to age-related decline in executive functions.

Purpose: In this review we discuss the broad clinical application of qAF and provide a descriptive summary of the phenotypic findings of different chorioretinal pathologies.Background: Quantitative Fundus autofluorescence (qAF) is a novel developing technology that can aid in diagnosis and longitudinal disease monitoring by measuring and comparing autofluorescence intensities. Fundus autofluorescence (FAF) is a noninvasive imaging method that creates a density map of the fluorophores of the ocular fundus and provides both functional and topographic anatomic information about retinal cells. Fluorophores are molecules that have the ability to temporarily absorb irradiated light, and emit a small amount of light of a different wavelength. Different endogenous fluorophores can be found in the ocular fundus. Changes in accumulation of retinal fluorophores usually indicate retinal pathology and create characteristic patterns of hyper-autofluorescence and hypo-autofluorescence that help establish a diagnosis.Conclusion: qAF allows a safe non-invasive visualization of the retina, enables a standard for AF intensities comparison and aids to the understanding of the genotype-phenotype correlations.

Retinitis pigmentosa (RP) is an inherited retinal disease affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high-acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a disease gene-agnostic therapy, we screened 20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb) and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.

BACKGROUND: Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP) that can cause impaired vision or blindness. Changes in blood lipids have been associated with ROP. This study aimed to monitor longitudinal changes in the serum sphingolipidome of extremely preterm infants and investigate the relationship to development of severe ROP. METHODS: This is a prospective study that included 47 infants born <28 gestational weeks. Serum samples were collected from cord blood and at postnatal days 1, 7, 14, and 28, and at postmenstrual weeks (PMW) 32, 36, and 40. Serum sphingolipids and phosphatidylcholines were extracted and analyzed by LC-MS/MS. Associations between sphingolipid species and ROP were assessed using mixed models for repeated measures. RESULTS: The serum concentration of all investigated lipid classes, including ceramide, mono- di- and trihexosylceramide, sphingomyelin, and phosphatidylcholine displayed distinct temporal patterns between birth and PMW40. There were also substantial changes in the lipid species composition within each class. Among the analyzed sphingolipid species, sphingosine-1-phosphate showed the strongest association with severe ROP, and this association was independent of gestational age at birth and weight standard deviation score change. CONCLUSIONS: The serum phospho- and sphingolipidome undergoes significant remodeling during the first weeks of the preterm infant's life. Low postnatal levels of the signaling lipid sphingosine-1-phosphate are associated with the development of severe ROP.

PRECIS: A cross-sectional sample of the US ophthalmology residency graduating class of 2018 revealed that 18.4% of residents logged <5 traditional glaucoma surgeries, and 63.4% logged at least 1 microinvasive glaucoma surgery (MIGS). PURPOSE: Describe the state of MIGS in US ophthalmology residency training and propose a glaucoma procedure classification system for residents' surgical case logs. METHODS: Deidentified case logs from residents graduating in 2018 were requested from US residency program directors. RESULTS: Case logs were received for 152/488 (31%) residents from 36/115 (31%) programs. The mean number of traditional glaucoma surgeries per resident was 9.0±5.9 (range: 0 to 31). The mean number of MIGS per resident was 5.2±8.9 cases (range: 0 to 58). There were 28/152 (18.4%) residents from 16/36 (44.4%) programs who logged <5 traditional glaucoma surgeries as primary surgeon, and 3/152 (2.0%) residents from 3/36 (8.3%) programs who logged zero traditional glaucoma surgeries as primary surgeon. There were 98/152 (64.5%) residents from 32/36 (88.8%) programs who logged <5 MIGS as primary surgeon, and 48/152 (31.6%) residents from 25 of 36 (69.4%) programs who logged zero MIGS as primary surgeon. There were 104/152 (63.4%) residents from 33/36 (91.6%) programs who logged at least 1 MIGS as primary surgeon; there were 3/36 (8.3%) residency programs where no resident logged any MIGS as primary surgeon. CONCLUSIONS: US ophthalmology residents' MIGS experience varies widely. Residents can satisfy glaucoma surgery requirements with some MIGS, even in the absence of adequate traditional glaucoma surgeries. We propose a residency case log classification system that better reflects the growing role of MIGS in clinical practice and helps ophthalmic educators more accurately track procedures requiring related skills.

PURPOSE: To compare the variability and ability to detect visual field (VF) progression of 24-2, central 12 locations of the 24-2 and 10-2 VF tests in eyes with abnormal VFs. DESIGN: Retrospective, multisite cohort. PARTICIPANTS: A total of 52 806 24-2 and 11 966 10-2 VF tests from 7307 eyes from the Glaucoma Research Network database were analyzed. Only eyes with ≥ 5 visits and ≥ 2 years of follow-up were included. METHODS: Linear regression models were used to calculate the rates of mean deviation (MD) change (slopes), whereas their residuals were used to assess variability across the entire MD range. Computer simulations (n = 10 000) based on real MD residuals of our sample were performed to estimate power to detect significant progression (P < 5%) at various rates of MD change. MAIN OUTCOME MEASURES: Time required to detect progression. RESULTS: For all 3 patterns, the MD variability was highest within the -5 to -20 decibel (dB) range and consistently lower with the 10-2 compared with 24-2 or central 24-2. Overall, time to detect confirmed significant progression at 80% power was the lowest with 10-2 VF, with a decrease of 14.6% to 18.5% when compared with 24-2 and a decrease of 22.9% to 26.5% when compared with central 24-2. CONCLUSIONS: Time to detect central VF progression was reduced with 10-2 MD compared with 24-2 and C24-2 MD in glaucoma eyes in this large dataset, in part because 10-2 tests had lower variability. These findings contribute to current evidence of the potential value of 10-2 testing in the clinical management of patients with glaucoma and in clinical trial design.

PURPOSE: To identify common causes of emergency department-treated eye injury among older adults in the United States (US), and to characterize of fall-related ocular trauma in this population. DESIGN: Retrospective cohort study METHODS: Data from the National Electronic Injury Surveillance System, a nationally representative database of US emergency department-treated injuries, was used to assemble a cohort of adults 65 years and older with eye injuries between January 1, 2000 and December 31, 2019. Demographic information, diagnosis, disposition, injury location and consumer product associated with injury were collected. Narrative descriptions of all injuries were reviewed to identify eye injuries secondary to falls. RESULTS: 4,953 eye injuries among older adults were reported from 2000 to 2019, a stratified probability sample representing approximately 238,162 injuries, with an average annual frequency of 12,000 injuries. Falls accounted for 11.5% of these injuries. Fall-related eye injuries commonly presented from home (66.5%) and were more likely to occur in the winter than eye injuries from other causes (28.1% vs. 18.4%, p<0.01). Risk factors for fall-related eye injury included older age (Odds ratio [OR] 1.11, 95% confidence intervals [CI] 1.10-1.13 per year), female sex (OR 2.3, 95% CI 1.6-3.1 vs. male), Black race (OR 2.4, 95% CI 1.3-4.5 vs. White) and presentation from a nursing home (OR 12.7, 95% CI 4.9-32.8 vs. other locations). Older adults with fall-related injury were more likely to be hospitalized (OR 22.8, 95% CI 15.3-33.9) and to suffer from a ruptured globe (OR 14.1, 95% CI 6.5-30.6) than those with fall-unrelated injury. CONCLUSIONS: Falls are an important mechanism of ocular trauma in older adults and are associated with worse outcomes compared to eye injuries from other causes.

Purpose: The purpose of this study was to determine whether YAP/TAZ activation in uveal melanoma (UM) and the susceptibility of melanoma cell lines to YAP/TAZ inhibition by verteporfin (VP) is related to the tumor's genetic background. Methods: Characteristics of 144 patients with enucleated UM were analyzed together with mRNA expression levels of YAP/TAZ-related genes (80 patients from the The Cancer Genome Atlas [TCGA] project and 64 patients from Leiden, The Netherlands). VP was administered to cell lines 92.1, OMM1, Mel270, XMP46, and MM28 (UM), CRMM1 and CRMM2 (conjunctival melanoma), and OCM3 (cutaneous melanoma). Viability, growth speed, and expression of YAP1-related proteins were assessed. Results: In TCGA data, high expression of YAP1 and WWTR1 correlated with the presence of monosomy 3 (P = 0.009 and P < 0.001, respectively) and BAP1-loss (P = 0.003 and P = 0.001, respectively) in the primary UM; metastasis development correlated with higher expression of YAP1 (P = 0.05) and WWTR1 (P = 0.003). In Leiden data, downstream transcription factor TEAD4 was increased in cases with M3/BAP1-loss (P = 0.002 and P = 0.006) and related to metastasis (P = 0.004). UM cell lines 92.1, OMM1, and Mel270 (GNAQ/11-mutation, BAP1-positive) and the fast-growing cell line OCM3 (BRAF-mutation) showed decreased proliferation after exposure to VP. Two slow-growing UM cell lines XMP46 and MM28 (GNAQ/11-mutation, BAP1-negative) were not sensitive to VP, and neither were the two conjunctival melanoma cell lines (BRAF/NRAS-mutation). Conclusions: High risk UM showed an increased expression of YAP/TAZ-related genes. Although most UM cell lines responded in vitro to VP, BAP1-negative and conjunctival melanoma cell lines did not. Not only the mutational background, but also cell growth rate is an important predictor of response to YAP/TAZ inhibition by VP.

PURPOSE: Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness. DESIGN: Retrospective analysis. PARTICIPANTS: Minimally invasive glaucoma surgeries and standard glaucoma surgeries recorded in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. METHODS: We used the data from IRIS Registry between 2013 and 2018 (inclusive) to measure the annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device [GDD] placement) performed in the United States, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique also were conducted. MAIN OUTCOME MEASURES: Trends and sociodemographic characteristics of MIGS use in the United States. RESULTS: Two hundred three thousand three hundred thirty-two eyes and 232 537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD), Ninth or Tenth Revision, codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, a substantial increase in annual MIGS procedures occurred over the study period (from 7586 in 2013 to 39 677) and a smaller decrease in standard glaucoma procedures (from 16 215 to 13 701). The proportion of iStent procedures almost tripled during the study period (from 14% to 40%), and by 2017 accounted for almost half (43.7%) of all glaucoma surgeries in the United States. Twenty-one thousand twenty-five of all eyes (10.3%) underwent multiple procedures: 7638 (36.3%) on the same day and 13 387 (63.7%) on subsequent days. Endocyclophotocoagulation and iStent placement were the most common concurrent procedures (55.4% of all concurrent procedures). Trabeculectomy and GDD placement were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, endocyclophotocoagulation and goniotomy were the most common procedures performed (33.0% and 21.9%, respectively). CONCLUSIONS: A significant increase in MIGS use occurred over the recent 6-year period, despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS versus traditional surgical treatments for glaucoma.

There is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.