Anomalous photochromism and mechanochromism of a linear naphthopyran enabled by a polarizing dialkylamine substituent.

In contrast to common angular naphthopyrans that exhibit strong photochromic and mechanochromic behavior, constitutionally isomeric linear naphthopyrans are typically not photochromic, due to the putative instability of the completely dearomatized merocyanine product. The photochemistry of linear naphthopyrans is thus relatively understudied compared to angular naphthopyrans, while the mechanochromism of linear naphthopyrans remains completely unexplored. Here we demonstrate that the incorporation of a polarizing dialkylamine substituent enables photochromic and mechanochromic behavior from polymers containing a novel linear naphthopyran motif. In solution phase experiments, a Lewis acid trap was necessary to observe accumulation of the merocyanine product upon photochemical and ultrasound-induced mechanochemical activation. However, the same linear naphthopyran molecule incorporated as a crosslinker in polydimethylsiloxane elastomers renders the materials photochromic and mechanochromic without the addition of any trapping agent. This study provides insights into the photochromic and mechanochromic reactivity of linear naphthopyrans that have conventionally been considered functionally inert, adding a new class of naphthopyran molecular switches to the repertoire of stimuli-responsive polymers.

Remote control of mechanochemical reactions under physiological conditions using biocompatible focused ultrasound.

External control of chemical reactions in biological settings with spatial and temporal precision is a grand challenge for noninvasive diagnostic and therapeutic applications. While light is a conventional stimulus for remote chemical activation, its penetration is severely attenuated in tissues, which limits biological applicability. On the other hand, ultrasound is a biocompatible remote energy source that is highly penetrant and offers a wide range of functional tunability. Coupling ultrasound to the activation of specific chemical reactions under physiological conditions, however, remains a challenge. Here, we describe a synergistic platform that couples the selective mechanochemical activation of mechanophore-functionalized polymers with biocompatible focused ultrasound (FUS) by leveraging pressure-sensitive gas vesicles (GVs) as acousto-mechanical transducers. The power of this approach is illustrated through the mechanically triggered release of covalently bound fluorogenic and therapeutic cargo molecules from polymers containing a masked 2-furylcarbinol mechanophore. Molecular release occurs selectively in the presence of GVs upon exposure to FUS under physiological conditions. These results showcase the viability of this system for enabling remote control of specific mechanochemical reactions with spatiotemporal precision in biologically relevant settings and demonstrate the translational potential of polymer mechanochemistry.

Naphthopyran molecular switches and their emergent mechanochemical reactivity.

Naphthopyran molecular switches undergo a ring-opening reaction upon external stimulation to generate intensely colored merocyanine dyes. Their unique modularity and synthetic accessibility afford exceptional control over their properties and stimuli-responsive behavior. Commercial applications of naphthopyrans as photoswitches in photochromic ophthalmic lenses have spurred an extensive body of work exploring naphthopyran-merocyanine structure-property relationships. The recently discovered mechanochromic behavior of naphthopyrans has led to their emergent application in the field of polymer mechanochemistry, enabling advances in the design of force-responsive materials as well as fundamental insights into mechanochemical reactivity. The structure-property relationships established in the photochemical literature serve as a convenient blueprint for the design of naphthopyran molecular force probes with precisely tuned properties. On the other hand, the mechanochemical reactivity of naphthopyran diverges in many cases from the conventional photochemical pathways, resulting in unexpected properties and opportunities for deeper understanding and innovation in polymer mechanochemistry. Here, we highlight the features of the naphthopyran scaffold that render it a powerful platform for the design of mechanochromic materials and review recent advances in naphthopyran mechanochemistry.

Lifestyle strategies after intentional weight loss: results from the MAINTAIN-pc randomized trial.

Introduction/Purpose: Weight maintenance following intentional weight loss is challenging and often unsuccessful. Physical activity and self-monitoring are strategies associated with successful weight loss maintenance. However, less is known about the type and number of lifestyle strategies used following intentional weight loss. The purpose of this study was to determine the types and amounts of strategies associated with successful long-term weight loss maintenance. Methods: Data from the 24-month Maintaining Activity and Nutrition Through Technology-Assisted Innovation in Primary Care (MAINTAIN-pc) trial were analyzed. MAINTAIN-pc recruited adults (n=194; 53.4±12.2 years of age, body mass index (BMI): 30.4±5.9 kg/m2, 74% female) with recent intentional weight loss of ≥5%, randomized to tracking tools plus coaching (i.e., coaching group) or tracking tools without coaching (i.e., tracking-only group). At baseline, 6, 12, and 24 months, participants reported lifestyle strategies used in the past 6 months, including self-monitoring, group support, behavioral skills, and professional support. General linear models evaluated changes in the number of strategies over time between groups and the consistency of strategies used over the 24-month intervention. Results: At baseline, 100% used behavioral skills, 73% used group support, 69% used self-monitoring, and 68% used professional support in the past 6 months; at 24 months, these rates were 98%, 60%, 75%, and 61%, respectively. While the number of participants utilizing individual strategies did not change significantly over time, the overall number of strategies participants reported decreased. More strategies were used at baseline and 6 months compared to 12- and 24-month follow-ups. The coaching group used more strategies at months 6 and 12 than the tracking-only group. Consistent use of professional support strategies over the 24-month study period was associated with less weight regain. Conclusion: Weight loss maintenance interventions that incorporate continued follow-up and support from healthcare professionals are likely to prevent weight regain after intentional weight loss.

Validation of an Accurate and Expedient Initial Rates Method for Characterizing Mechanophore Reactivity.

Understanding structure-mechanochemical reactivity relationships is important for informing the rational design of new stimuli-responsive polymers. To this end, establishing accurate reaction kinetics for mechanophore activation is a key objective. Here, we validate an initial rates method that enables the accurate and rapid determination of rate constants for ultrasound-induced mechanochemical transformations. Experimental reaction profiles are well-aligned with theoretical models, which support that the initial rates method effectively deconvolutes the kinetics of specific mechanophore activation from the competitive process of nonspecific chain scission.

Mechanical Force Enables an Anomalous Dual Ring-Opening Reaction of Naphthodipyran.

Multimodal mechanophores that exhibit complex mechanochromic behavior beyond the typical binary response are capable of distinguishing between multiple stress states through discrete changes in color. Naphthodipyran photoswitches contain two pyran rings fused to a central naphthalene core and represent a potentially promising framework for multimodal reactivity. However, the concurrent ring opening of both pyran moieties has previously proven inaccessible via photochemical activation. Here, we demonstrate that mechanical force supplied to naphthodipyran through covalently linked polymer chains generates the elusive dual ring-opened dimerocyanine product with unique near-infrared absorption properties. Trapping with boron trifluoride renders the merocyanine dyes thermally persistent and reveals apparent sequential ring-opening behavior that departs from the reactivity of previously studied mechanophores under the high strain rates imposed by ultrasound-induced solvodynamic chain extension.

Is the Activity Measure for Postacute Care "6-Clicks" Tool Associated With Discharge Destination Postacute Stroke?

Objective: To investigate the association of poststroke physical function, measured within 24 hours prior to discharge from the acute care hospital using Activity Measure for Postacute Care (AM-PAC) Inpatient "6-Clicks" scores and discharge destination (home vs facility and inpatient rehabilitation facility [IRF] vs skilled nursing facility [SNF]). Design: Retrospective cross-sectional cohort study. Setting: Acute care, University Hospital. Participants: Individuals post acute ischemic stroke, N=721, 51.3% male, mean age 63.6±16.4 years. Interventions: Not applicable. Main Outcome Measures: AM-PAC "6-Clicks" 3 domains: basic mobility, daily activity, and applied cognition. Results: AM-PAC basic mobility and daily activity were significant predictors of discharge. Those in the home discharge group had AM-PAC basic mobility mean t scale score of 48.5 compared with a score of 34.8 for individuals sent to a facility and daily activity score of 47.2 compared with 32.7 for individuals sent to a facility. The AM-PAC variables accounted for an additional 24% of the variance in the discharge destination, with basic mobility and daily activity accounting for most of the variance.The AM-PAC scores were not statistically different and were not able to discriminate between placement in an IRF vs SNF. The mean basic mobility t scale score for individuals going to an IRF was 34.9 compared with 34.6 for those going to an SNF. The daily activity score for IRF was 32.8 compared with 32.6 for SNF. The AM-PAC accounted for no additional variance in discharge destination to an IRF or SNF. Conclusions: The AM-PAC Inpatient "6-Clicks" 3 domains are able to distinguish individuals with stroke being discharged to home from postacute care (PAC) but not for differentiating between PAC facilities (IRF vs SNF) in this cohort of individuals post stroke.

Changes in Pain Catastrophizing and Fear-Avoidance Beliefs as Mediators of Early Physical Therapy on Disability and Pain in Acute Low-Back Pain: A Secondary Analysis of a Clinical Trial.

OBJECTIVE: The Fear-Avoidance Model (FAM) of chronic pain posits that pain catastrophizing and fear-avoidance beliefs are prognostic for disability and chronicity. In acute low-back pain, early physical therapy (PT) is effective in reducing disability in some patients. How early PT impacts short- and long-term changes in disability for patients with acute pain is unknown. Based on the FAM, we hypothesized that early reductions in pain catastrophizing and fear-avoidance beliefs would mediate early PT's effect on changes in disability (primary outcome) and pain intensity (secondary outcome) over 3 months and 1 year. SUBJECTS: Participants were 204 patients with low-back pain of <16 days duration, who enrolled in a clinical trial (NCT01726803) comparing early PT sessions or usual care provided over 4 weeks. METHODS: Patients completed the Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ work and physical activity scales), and outcomes (Oswestry Disability Index and Numeric Pain Rating Scale) at baseline, 4 weeks, 3 months, and 1 year. We applied longitudinal mediation analysis with single and multiple mediators. RESULTS: Early PT led to improvements in disability and pain over 3 months but not 1 year. In the single mediator model, 4-week reductions in pain catastrophizing mediated early PT's effects on 3-month disability and pain intensity improvements, explaining 16% and 22% of the association, respectively, but the effects were small. Pain catastrophizing and fear-avoidance beliefs did not jointly mediate these associations. CONCLUSIONS: In acute low-back pain, early PT may improve disability and pain outcomes at least partly through reducing patients' catastrophizing.

Amino acid divergence in the ligand-binding pocket of Vibrio LuxR/HapR proteins determines the efficacy of thiophenesulfonamide inhibitors.

The quorum-sensing signaling systems in Vibrio bacteria converge to control levels of the master transcription factors LuxR/HapR, a family of highly conserved proteins that regulate gene expression for bacterial behaviors. A compound library screen identified 2-thiophenesulfonamide compounds that specifically inhibit Vibrio campbellii LuxR but do not affect cell growth. We synthesized a panel of 50 thiophenesulfonamide compounds to examine the structure-activity relationship effects on Vibrio quorum sensing. The most potent molecule identified, PTSP (3-phenyl-1-(thiophen-2-ylsulfonyl)-1H-pyrazole), inhibits quorum sensing in multiple strains of V. vulnificus, V. parahaemolyticus, and V. campbellii at nanomolar concentrations. However, thiophenesulfonamide inhibition efficacy varies significantly among Vibrio species: PTSP is most inhibitory against V. vulnificus SmcR, but V. cholerae HapR is completely resistant to all thiophenesulfonamides tested. Reverse genetics experiments show that PTSP efficacy is dictated by amino acid sequence in the putative ligand-binding pocket: F75Y and C170F SmcR substitutions are each sufficient to eliminate PTSP inhibition. Further, in silico modeling distinguished the most potent thiophenesulfonamides from less-effective derivatives. Our results revealed the previously unknown differences in LuxR/HapR proteins that control quorum sensing in Vibrio species and underscore the potential for developing thiophenesulfonamides as specific quorum sensing-directed treatments for Vibrio infections.

The Relationship Between Neighborhood Deprivation and Perceived Changes for Pain-Related Experiences Among US Patients with Chronic Low Back Pain During the COVID-19 Pandemic.

OBJECTIVE: Disruptions caused by the COVID-19 pandemic could disproportionately affect the health of vulnerable populations, including patients experiencing persistent health conditions (i.e., chronic pain), along with populations living within deprived, lower socioeconomic areas. The current cross-sectional study characterized relationships between neighborhood deprivation and perceived changes in pain-related experiences during the COVID-19 pandemic (early-September to mid-October 2020) for adult patients (N = 97) with nonspecific chronic low back pain. METHODS: We collected self-report perceived experiences from participants enrolled in an ongoing pragmatic randomized trial across medical centers within the Salt Lake City, Utah and Baltimore, Maryland metropolitans. The Area Deprivation Index (composite of 17 US Census deprivation metrics) reflected neighborhood deprivation based on participants' zip codes. RESULTS: Although those living in the neighborhoods with greater deprivation endorsed significantly poorer physical (pain severity, pain interference, physical functioning), mental (depression, anxiety), and social health during the pandemic, there were no significant differences for perceived changes in pain-related experiences (pain severity, pain interference, sleep quality) between levels of neighborhood deprivation since the onset of the pandemic. However, those in neighborhoods with greater deprivation endorsed disproportionately worse perceived changes in pain coping, social support, and mood since the pandemic. CONCLUSIONS: The current findings offer evidence that changes in pain coping during the pandemic may be disproportionately worse for those living in deprived areas. Considering poorer pain coping may contribute to long-term consequences, the current findings suggest the need for further attention and intervention to reduce the negative effect of the pandemic for such vulnerable populations.

Generation of an Elusive Permanent Merocyanine via a Unique Mechanochemical Reaction Pathway.

We report the discovery of a 2H-naphtho[1,2-b]pyran mechanophore that produces a permanent merocyanine dye upon mechanochemical activation, in contrast to the reversible product generated photochemically. Experiments suggest that the irreversibility of the mechanically generated merocyanine is due to a unique reaction in which the scission of an ester C-O bond reveals a ß-hydroxy ketone that locks the merocyanine through an intramolecular H-bonding interaction. In addition to demonstrating the reactivity using solution-phase ultrasonication, permanent merocyanine generation is also achieved in solid polymeric materials. The permanent coloration achieved with the naphthopyran mechanophore affords unique opportunities for sensing and force-recording applications as well as fundamental studies limited by the reversibility of typical colorimetric force probes.

Optimization of Spinal Manipulative Therapy Protocols: A Factorial Randomized Trial Within a Multiphase Optimization Framework.

Spinal manipulative therapy (SMT) is a common nonpharmacological treatment for low back pain (LBP). Although generally supported by systematic reviews and practice guidelines, clinical trials evaluating SMT have been characterized by small effect sizes. This study adopts a Multiphase Optimization Strategy framework to examine individual components of an SMT delivery protocol using a single-blind trial with the goal of identifying and optimizing a multicomponent SMT protocol. We enrolled 241 participants with LBP. All participants received 2 SMT treatment sessions in the first week then were randomly assigned additional treatment based on a fully factorial design. The 3 randomized treatment components provided in twice weekly sessions over 3 weeks were multifidus activating exercise, spinal mobilizing exercise, and additional SMT dose. Primary outcomes included clinical (Oswestry Disability Index, numeric pain intensity rating) and mechanistic (spinal stiffness, multifidus muscle activation) measures assessed at baseline, 1, 4, and 12 weeks. Significant differences were found for the Oswestry index after 12 weeks for participants receiving multifidus activating exercise (mean difference = -3.62, 97.5% CI: -6.89, -0.35; P= .01). There were no additional significant main or interaction effects for other treatment components or different outcome measures. The optimized SMT protocol identified in this study included SMT sessions followed by multifidus activating exercises. PERSPECTIVE: Optimizing the effects of nonpharmacological treatments such as SMT for LBP is challenging due to uncertainty regarding mechanisms and the complexity of multicomponent protocols. This factorial randomized trial examined SMT protocols provided with differing co-interventions with mechanistic and patient-centered outcomes. Patient-centered outcomes were optimized by inclusion of lumbar multifidus strengthening exercises.

Physical Therapy Referral From Primary Care for Acute Back Pain With Sciatica : A Randomized Controlled Trial.

BACKGROUND: Few studies have examined primary care management for acute sciatica, including referral to physical therapy. OBJECTIVE: To evaluate whether early referral to physical therapy reduced disability more than usual care (UC) alone for patients with acute sciatica. DESIGN: Randomized controlled clinical trial. (ClinicalTrials.gov: NCT02391350). SETTING: 2 health care systems in Salt Lake City, Utah. PATIENTS: 220 adults aged 18 to 60 years with sciatica of less than 90 days' duration who were making an initial primary care consultation. INTERVENTION: All participants received imaging and medication at the discretion of the primary care provider before enrollment. A total of 110 participants randomly assigned to UC were provided 1 session of education, and 110 participants randomly assigned to early physical therapy (EPT) were provided 1 education session and then referred for 4 weeks of physical therapy, including exercise and manual therapy. MEASUREMENTS: The primary outcome was the Oswestry Disability Index (OSW) score after 6 months. Secondary outcomes were pain intensity, patient-reported treatment success, health care use, and missed workdays. RESULTS: Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, -5.4 points [95% CI, -9.4 to -1.3 points]; P = 0.009). The OSW and several secondary outcomes favored EPT after 4 weeks. After 1 year, between-group differences favored EPT for the OSW (relative difference, -4.8 points [CI, -8.9 to -0.7 points]) and back pain intensity (relative difference, -1.0 points [CI, -1.6 to -0.4 points]). The EPT group was more likely to self-report treatment success after 1 year (45.2%) than the UC group (27.6%) (relative risk, 1.6 [CI, 1.1 to 2.4]). There were no significant differences in health care use or missed workdays. LIMITATION: The patients and providers were unblinded, and specific physical therapy interventions responsible for effects could not be determined. CONCLUSION: Referral from primary care to physical therapy for recent-onset sciatica improved disability and other outcomes compared with UC. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

A Comparison Between the Clinical Features of Pseudotumor Cerebri Secondary to Tetracyclines and Idiopathic Intracranial Hypertension.

PURPOSE: Comparisons between clinical features of tetracycline-induced pseudotumor cerebri (PTC-T) and those of idiopathic intracranial hypertension (IIH) are absent in the literature. We hypothesized that significant clinical differences between these etiologies exist and could be better understood by retrospective analysis. DESIGN: Retrospective cohort study. METHODS: We reviewed patients diagnosed with pseudotumor cerebri syndrome (PTCS) at our center and identified those who developed PTC-T after treatment with a tetracycline-class antibiotic and those with IIH. Groups were compared by demographics, body mass index, ophthalmic examination, treatment, clinical course, and visual outcomes. RESULTS: We identified 52 cases of PTC-T and 302 cases of IIH. Obesity rates were significantly different (43.8% for PTC-T vs 79.2% for IIH, P < .001). The mean age at diagnosis was younger for PTC-T (19.8 years vs 28.1 years for IIH, P < .001). Diplopia was more common with PTC-T (40.4% vs 20.1% for IIH, P = .001). The mean illness duration was shorter for PTC-T (18.3 weeks vs 62.9 weeks for IIH, P <.0001). Recurrence rates were significantly different (4.0% for PTC-T vs 16.5% for IIH, P <.001). The frequency of surgical intervention was similar. Vision loss was uncommon but occurred with similar frequency. CONCLUSION: We identified significant clinical differences but also identified important similarities between the 2 groups. There appear to be nonobese patients who develop PTC-T, discontinue the antibiotic, and never develop PTCS again. There are other patients who develop PTC-T, discontinue the antibiotic, and later develop IIH. We conclude that PTC-T represents a spectrum of disease in susceptible individuals.

Prevalence of Retinal Diseases and Associated Risk Factors in an African Population From Mwanza, Tanzania.

BACKGROUND AND OBJECTIVE: To determine the prevalence of retinal disease among a population in Mwanza, Tanzania, and to identify relevant risk factors for retinal disorders in this cohort. PATIENTS AND METHODS: A cross-sectional population-based study was conducted in Mwanza, Tanzania, among patients older than 18 years. Participants completed a demographics survey and underwent an ophthalmic examination that included fundus photography. RESULTS: Complete data were available for 1,007 (93.8%) of the 1,073 persons examined. The prevalence of vitreoretinal disorders was 22.8% (230/1,007). The leading retinal diseases were age-related macular degeneration (7.0%), hypertensive retinopathy (4.5%), and macular scars (2.7%). CONCLUSION: This study is the first population-based study of retinal disease in Mwanza. The findings reveal a considerable burden of retinal disease in this region, suggesting a need for trained local ophthalmic personnel and resources. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S17-S25.].

A metabolic pathway for bile acid dehydroxylation by the gut microbiome.

The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 µM and are known to block the growth of Clostridium difficile1, promote hepatocellular carcinoma2 and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref. 3). More broadly, DCA, LCA and their derivatives are major components of the recirculating pool of bile acids4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Nonetheless, despite the clear impact of DCA and LCA on host physiology, an incomplete knowledge of their biosynthetic genes and a lack of genetic tools to enable modification of their native microbial producers limit our ability to modulate secondary bile acid levels in the host. Here we complete the pathway to DCA and LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the eight-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a nonproducing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool.

Designing naphthopyran mechanophores with tunable mechanochromic behavior.

Mechanochromic molecular force probes conveniently report on stress and strain in polymeric materials through straightforward visual cues. We capitalize on the versatility of the naphthopyran framework to design a series of mechanochromic mechanophores that exhibit highly tunable color and fading kinetics after mechanochemical activation. Structurally diverse naphthopyran crosslinkers are synthesized and covalently incorporated into silicone elastomers, where the mechanochemical ring-opening reactions are achieved under tension to generate the merocyanine dyes. Strategic structural modifications to the naphthopyran mechanophore scaffold produce dramatic differences in the color and thermal electrocyclization behavior of the corresponding merocyanine dyes. The color of the merocyanines varies from orange-yellow to purple upon the introduction of an electron donating pyrrolidine substituent, while the rate of thermal electrocyclization is controlled through electronic and steric factors, enabling access to derivatives that display both fast-fading and persistent coloration after mechanical activation and subsequent stress relaxation. In addition to identifying key structure-property relationships for tuning the behavior of the naphthopyran mechanophore, the modularity of the naphthopyran platform is demonstrated by leveraging blends of structurally distinct mechanophores to create materials with desirable multicolor mechanochromic and complex stimuli-responsive behavior, expanding the scope and accessibility of force-responsive materials for applications such as multimodal sensing.

Force-Dependent Multicolor Mechanochromism from a Single Mechanophore.

We report a bis-naphthopyran mechanophore that exhibits force-dependent changes in visible absorption. A series of polymers incorporating a chain-centered bis-naphthopyran mechanophore was synthesized and mechanically activated using ultrasonication. By varying the length of the polymer chains, the force delivered to the mechanophore is modulated systematically. We demonstrate that the relative distribution of two distinctly colored merocyanine products is altered predictably with different magnitudes of applied force, resulting in gradient multicolor mechanochromism. The mechanochemical reactivity of bis-naphthopyran is supported by density functional theory calculations and described by a theoretical model that provides insight into the force-color relationship.

Association of electroretinography with visual outcomes after ophthalmic artery chemosurgery for retinoblastoma in ICRb D and E eyes.

IMPORTANCE: Predictions of visual outcomes are useful in clinical and family decisions regarding treatment for retinoblastoma. Very little has been published on the association of post-treatment visual acuity with pre-treatment electroretinography (ERG), which can be performed on infants too young to reliably quantify visual acuity. OBJECTIVE: To report associations of pre-treatment ERG with post-treatment visual acuity in eyes with advanced retinoblastoma treated with ophthalmic artery chemosurgery (OAC). DESIGN: Retrospective case-control study of eyes treated from 2006 through 2017, with mean follow-up of 51 months (range 2.3-150 months). SETTING: Single large academic center. PARTICIPANTS: Group D and E eyes treated with OAC at Memorial Sloan Kettering Cancer Center with recorded visual acuity and ERG (30Hz flicker). MAIN OUTCOME AND MEASURE: Snellen visual acuity (uncorrected) compared to initial 30Hz flicker ERG. RESULTS: This study included 157 Group D and E eyes. Results of the Jonckheere-Terpstra test for trend were statistically significant and indicated that eyes with lower pre-treatment ERG readings tended to have more visual impairment post-treatment. Among eyes with initial ERG 75+ µV, 11 of 32 eyes (34%) had visual acuity 20/40 or better. Among eyes with ERG 0 µV, 44 of 46 (96%) had visual acuity of 20/200 or worse. CONCLUSIONS AND RELEVANCE: Eyes with advanced intraocular retinoblastoma treated with OAC can achieve excellent visual acuity, but poor ERG at initial visit is associated with poor visual acuity after treatment in the majority of eyes. Expectations regarding visual potential may influence decisions about treatment.