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Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers.Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment.The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94).These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

Models of addiction are based on neurobiological, behavioral, and pharmacological studies in animals, but translational support from human studies is limited. Studies are lacking in examining acute responses to alcohol in drinkers with alcohol use disorder (AUD), particularly in terms of relevant intoxicating doses and measurement of stimulating and rewarding effects throughout the breath alcohol concentration (BrAC) time curve. Participants were N = 60 AUD drinkers enrolled in the Chicago Social Drinking Project and examined in three random-order and blinded sessions for subjective and physiological responses to a beverage containing 0.0 g/kg, 0.8 g/kg, and 1.2 g/kg alcohol. BrAC in the alcohol sessions at 60 min was 0.09 g/dL and 0.13 g/dL, respectively. Both doses of alcohol produced significant biphasic effects on subjective measures of stimulation, euphoria, reward (liking and wanting), sedation, and neuroendocrine and cardiovascular factors. Increased pleasurable effects of alcohol were pronounced during the rising limb-to-peak BrAC and sedating effects emerged during the declining limb. Alcohol dose-dependently increased feel drug ratings and rewarding effects at peak BrAC or early declining limb, and physiological responses at the rising limb. Thus, rather than the notion of an overall tolerance, results show an alcohol response phenotype characterized by sensitivity to alcohol's stimulating, rewarding and physiological effects. The results of this study may aid in the conceptualization of alcohol addiction as a disorder characterized by the persistence of enhanced hedonic alcohol responses rather than chronic tolerance and reward deficiency.

Introduction To evaluate the refractive outcome of combined cataract extraction and glaucoma drainage device (GDD) surgery. Methods Patients who had undergone combined phacoemulsification with GDD surgery [Baerveldt, Abbott Medical, Abbott Park (IL) or Ahmed valve, New World Medical, Rancho Cucamonga (CA)] between June 2009 and August 2017 were included in the study. The main outcome measure evaluated was whether or not spherical equivalent (SE) between ± 1D from target refraction was achieved at 3–6 months postoperatively. Results The final analysis included 42 eyes of 38 patients who underwent combined phacoemulsification and GDD surgery. A refractive outcome of spherical equivalent (SE) between ± 1D of the target refraction was achieved in 30 of 42 eyes (71.43%) at 3–6 months after surgery. Mean preoperative axial length (AL) of eyes with postoperative SE outside ± 1D from target (SD = 0.98, p = 0.003) was noted to be 25.37 ± 0.98 mm (longer mean AL) and that of eyes with SE between ± 1D (SD = 0.89, p = 0.000) was found to be 23.34 ± 0.89 mm (average mean AL). Twelve (29%) eyes were noted to have a mean 0.52D (SD = 0.49; range 0.02–1.49) of corneal astigmatism induced by combined surgery. Age, central corneal thickness, preoperative anterior chamber depth, and pre- and postoperative intraocular pressure did not significantly affect refractive outcomes. Conclusion Refractive outcomes within 1.00D of the target refraction were achieved in most patients undergoing a combined surgical approach. Longer AL was a risk factor among patients with refractive change > 1.00D from target.

Subjective responses to alcohol play a key role in the development and maintenance of risky drinking and alcohol use disorder (AUD). The social and environmental context where drinking occurs may moderate alcohol's subjective effects, but ecologically valid studies of these associations are limited. The present study used high-resolution ecological momentary assessment (HR-EMA) targeting real-world binge drinking episodes to examine associations among drinking context, alcohol consumption, and subjective responses to alcohol.Young adult heavy drinkers (Most (85%) participants reported binge drinking during real-world drinking events. Estimated blood alcohol concentration (eBAC) and alcohol stimulation and reward (liking, wanting) were greater when participants drank with others (vs. alone) and in a bar/restaurant (vs. other location). Sedation was higher when drinking alone versus with others.The present study extends prior laboratory-based research and shows that subjective responses during naturalistic binge drinking episodes may be influenced by drinking context. Drinking with others and in bars and restaurants may increase alcohol consumption, enhance alcohol's rewarding effects, and lead to more alcohol-related harm in at-risk drinkers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

We assessed how rod excitation (R) affects luminance (L + M + S) and chromatic [L/(L + M)] reaction times (RTs). A four-primary display based on the overlapped images of two spectrally modified monitors, which allowed specific or combined [L + M + S + R, L/(L + M) + R] photoreceptor stimulation, was used to present a C-target stimulus differing from the background only by the selected stimulation. For the luminance pathway, rod input increased RTs, suggesting a suppressive rod–cone interaction. The responses of the chromatic pathway were faster when rods were involved, suggesting a major role of rods in mesopic color perception.

Color theory is based on the exclusive activation of cones. However, since the discovery of melanopsin expressing cells in the human retina, evidence of its intrusion in brightness and color vision is increasing. We aimed to assess if differences between peripheral or large field and foveal color matches can be accounted for by melanopsin activation or rod intrusion. Photopic color matches by young observers showed that differences between extrafoveal and foveal results cannot be explained by rod intrusion. Furthermore, statistical analyses on existing color-matching functions suggest a role of melanopsin activation, particularly, in large field S fundamentals.

Samiksha Fouzdar-Jain,1 Zena Ibrahim,2 Jeremy Reitinger,3 Dingcai Cao,2 Mehmet C Mocan2 1Department of Pediatric Ophthalmology & Adult Strabismus, Children’s Hospital and Medical Center, Omaha, NE, USA; 2Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA; 3Creighton University School of Medicine, Omaha, NE, USACorrespondence: Samiksha Fouzdar-JainDepartment of Pediatric Ophthalmology & Adult Strabismus, Children’s Hospital and Medical Center, Omaha, NE, USAEmail sjain@childrensomaha.orgPurpose: This study aimed to evaluate the visual outcomes of pediatric patients diagnosed with Peters anomaly (PA) in a tertiary eye care center.Methods: This was a retrospective study undertaken at a single academic center. Clinical records of pediatric patients diagnosed with PA from 2000 to 2017 were reviewed. Parameters recorded included visual acuity (VA), intraocular pressure (IOP), presence of glaucoma, and surgical procedures performed. The impact of PA type on final visual acuity levels was analyzed using generalized estimation equation models.Results: Twenty-one eyes from 11 patients were analyzed. At the final visit, 9 eyes (42.8%) had a VA ≥ 20/200, while 12 (57%) had < 20/200, ranging from 20/250 to no light perception. Of the study cohort, 15 (71.5%) eyes had type I, while six (28.5%) had type II PA. Glaucoma was present in 20 eyes (95%) at the final visit. One eye had dense central leucoma and microphthalmos where IOP could not be measured accurately. Seventeen eyes (81%) underwent at least one intraocular surgery, while the average number of surgeries per eye was 2.9 ± 2.5 (range=0– 9). The type of PA beta(se)=0.53 (0.41),p= 0.20] was not found to be a significant risk factor for worse VA.Conclusion: Severe visual impairment develops in the majority of patients with PA. The type of anomaly does not appear to be associated with a worse visual function in patients with PA. Glaucoma develops in a high percentage of this patient population, and thus close monitoring of IOP in this patient population is crucial.Keywords: Peters anomaly, penetrating keratoplasty, visual outcomes, logMAR, corneal opacity

Background For decades, laboratory alcohol challenges have been the "gold standard" for measuring individual differences in alcohol's subjective effects. However, these approaches are expensive and labor-intensive, making them impractical for large-scale use. This study examined the reliability and validity of a new high-resolution EMA (HR-EMA) ambulatory approach to assessing alcohol use and subjective responses in drinkers' natural environments. Methods Participants were 83 young adult heavy social drinkers (58% male; mean ± SD age = 25.4 ± 2.6 years) who completed up to two smartphone-based, 3-h HR-EMA assessments of alcohol use and related subjective responses in their typical drinking environments. Reported alcohol consumption during the HR-EMA periods was used to calculate estimated blood alcohol concentration (eBAC). Subjective effects were measured using the Brief Biphasic Alcohol Effects Scale (B-BAES) and Drug Effects Questionnaire (DEQ). All participants also completed identical measures during a separate, 4 to 5-h laboratory session in which they received a 0.8 g/kg alcohol challenge. Results Most natural environment drinking episodes (87%) met or exceeded the threshold for binge drinking (final mean eBAC = 0.12 g/dl). Associations between reported alcohol use and subjective responses on the B-BAES and DEQ were strongest earlier in the drinking events, with fair reliability of reported subjective effects across two HR-EMA episodes (intraclass correlation [ICC] range = 0.46-0.49). There was fair-to-good correspondence between HR-EMA- and laboratory-derived subjective responses (ICC range = 0.49-0.74), even after accounting for differences in alcohol consumption and drinking context. Reported stimulating and rewarding alcohol effects were higher in the ambulatory than laboratory setting, and vice versa for sedating effects. Conclusions This study supports the reliability and validity of smartphone-based HR-EMA to measure alcohol use and subjective responses in heavy drinkers' natural environments. These findings lend support to the use of ambulatory HR-EMA as a measure of alcohol subjective responses in risky drinkers when a laboratory protocol is not practical, feasible, or safe.

Purpose To describe international scleral lens prescription and management practices across multiple practice types. Methods For this cross-sectional study, scleral lens practitioners were asked to complete an electronic survey that requested information about a single scleral lens patient. Data collected included practitioner demographics (practice type, country, years of experience) and patient indications for scleral lens wear, fitting process, lens design, and care products. Results Data were collected for 259 patients (419 eyes). Most participants (60%) practiced in the US, 75% worked primarily in community practice, and 58% claimed more than 5 years’ experience fitting scleral lenses. Indications for scleral lens wear were corneal irregularity (87%), ocular surface disease (9%), and uncomplicated refractive error (4%). During the fitting process, the mean (SD) number of lenses ordered was 2.4 (1.6) (range, 1–16 lenses) during 3.8 (2.4) visits (range, 1–18 visits). Of patients, 62% used a daily surfactant cleaner, 47% used hydrogen peroxide disinfection, and 67% used single-use vials of nonpreserved saline. Mean lens diameter was 16.2 (1.1) mm (range, 11.8–23.0 mm). The landing zones were spherical (64%), toric (26%), quadrant-specific (7%), and custom (3%) designs. Optical power was spherical in 70%, toric in 27%, and higher-order aberration correcting in 3% of lenses. Only 5 lenses had multifocal optics. Conclusions General consensus regarding prescribing patterns (lens design, wearing schedules, care products) between US vs non-US, community vs academic, and new vs established providers is reported in this study. Relatively low percentages of patients wearing lenses with advanced landing zones or optical designs suggest that these new options have not been widely adopted.

Purpose To estimate the prevalence of patient-reported midday fogging and to identify risk factors for midday fogging. Method A multicenter, cross-sectional study was conducted with an electronic survey that was distributed to scleral lens practitioners. The survey asked them to describe their most recently examined established scleral lens patient. Respondents provided data about patient-reported midday fogging, patient demographic characteristics, indication for lens wear, lens-wearing schedule, lens design, and care products. Results Of the 248 survey respondents who indicated whether their patients had midday fogging, 64 (25.8 %) had patients who self-reported such issues. Midday fogging was not associated with demographic characteristics (age, sex, race/ethnicity), indications for scleral lens wear, mean lens diameter (P = .30), haptic design (P = .29), use of a daily cleaner (P = .12), disinfection/storage solution used (P = .71), or filling solution (P = .65). Patients who reported midday fogging more commonly reported redness or irritation associated with scleral lens wear compared with those who did not experience midday fogging (P = .03). Conclusions Prevalence of midday fogging in this study was similar to previously reported rates. No specific lens design or care product was associated with patient-reported midday fogging. If inflammatory mediators are elevated in the postlens fluid reservoir of patients with midday fogging, as previously described, the redness or irritation associated with scleral lens wear suggests that ocular surface inflammation may be contributing to this phenomenon.

INTRODUCTION: There remains a paucity of research quantifying alcohol’s effects in drinkers with alcohol use disorder (AUD), particularly responses to very high alcohol doses (≥0.8 g/kg). As drinkers with AUD frequently engage in very heavy drinking (8-10 drinks/occasion), doses of ≤0.8 g/kg may lack ecological validity. The present study examined the feasibility, tolerability, and safety of administering a very high alcohol dose (1.2 g/kg) to non-treatment seeking AUD participants. METHODS: Sixty-one young-adult AUD drinkers enrolled in the Chicago Social Drinking Project and completed three laboratory sessions at which they consumed a beverage with 1.2 g/kg, 0.8 g/kg, and 0.0 g/kg alcohol. Physiological responses (vital signs, nausea and vomiting, breath alcohol concentrations (BrAC)) were monitored throughout the sessions. After each session, participants completed a next-day survey of substance use, engagement in risky behaviors, and related consequences. RESULTS: Overall, the sample demonstrated good compliance with study procedures; 93% of participants adhered to pre-session alcohol abstinence requirements (indicated by BrAC

Color theory is based on the exclusive activation of cones. However, since the discovery of melanopsin expressing cells in the human retina, evidence of its intrusion in brightness and color vision is increasing. We aimed to assess if differences between peripheral or large field and foveal color matches can be accounted for melanopsin activation or rod intrusion. Photopic color matches by young observers showed that differences between extrafoveal and foveal results cannot be explained by rod intrusion. Furthermore, statistical analyses on existing color matching functions suggest a role of melanopsin activation, particularly, in Large Field S Fundamentals.

The concurrent use of both tobacco and alcohol causes substantial disease and early mortality, and smokers who drink heavily tend to be less successful in smoking cessation than smokers who do not. Although varenicline combined with nicotine replacement therapy for smoking cessation has been examined among smokers who do not drink heavily, this combination treatment has not yet been examined among smokers who drink heavily.To determine whether combined treatment with varenicline tartrate and nicotine patch improves continuous abstinence from cigarette smoking among smokers who drink heavily.This double-blind, placebo-controlled, superiority randomized clinical trial evaluated combined treatment with varenicline and nicotine patch compared with placebo and nicotine patch for smoking cessation (primary outcome) and drinking behavior (secondary outcome) among smokers who drink heavily. The clinical trial was conducted at 2 outpatient sites in Chicago, Illinois, with enrollment from March 26, 2018, to February 14, 2020. The 122 participants were recruited from the community via social media and public transit advertisements and equally randomized to the 2 treatment groups, which were stratified by sex and smoking behavior. Eligible participants smoked between 5 and 30 cigarettes per day and drank heavily (14 drinks per week for men or7 drinks per week for women and ≥1 heavy drinking day [defined as5 drinks per occasion for men or4 drinks per occasion for women] per month for the past year) and had a desire to quit smoking.Varenicline tartrate, 1.0 mg, twice daily or matching placebo pills twice daily for 12 weeks. Nicotine patch at manufacturer-recommended doses for 10 weeks and brief individual smoking cessation counseling the week before the quit date and on the quit date.The primary outcome was self-reported continuous cigarette abstinence through weeks 9 to 12; abstinence was biochemically confirmed at the week 12 study visit. Secondary outcomes were the frequency of weekly drinking and weekly heavy drinking during the study period.Among 122 participants (mean [SD] age, 44.0 [12.4] years; 67 men [54.9%]), 61 were randomly assigned to receive combined treatment with varenicline and nicotine patch (varenicline group), and 61 were randomly assigned to receive placebo and nicotine patch (placebo group). A total of 54 participants (44.3%) self-identified as Black, 56 (45.9%) as White, and 12 (9.8%) as other races (including American Indian or Alaska Native, Asian,1 race, and unspecified race). A total of 8 participants (6.6%) self-identified as Hispanic and 114 (93.4%) as non-Hispanic ethnicity. Study retention to 12 weeks was 89%. The intention-to-treat analyses showed higher smoking cessation rates during weeks 9 to 12 in the varenicline group vs the placebo group (27 participants [44.3%] vs 17 participants [27.9%]; odds ratio, 2.20; 95% CI, 1.01-4.80; P = .047) and lower likelihood of relapse throughout treatment in the varenicline group relative to the placebo group (hazard ratio, 0.62; 95% CI, 0.40-0.96; P = .03). Both treatments were well tolerated; however, compared with participants in the placebo group, those in the varenicline group experienced more adverse effects, with 5 participants in the varenicline group discontinuing medication due to adverse effects.In this study, combined treatment with varenicline and nicotine patch was more effective than placebo and nicotine patch for smoking cessation among smokers who drink heavily. The combination treatment had no effect on alcohol consumption, with both groups showing significant reductions. Combination treatment with varenicline and nicotine patch may be a viable option for smokers who drink heavily.ClinicalTrials.gov Identifier: NCT02859142.

SIGNIFICANCE Scleral lenses (SLs) are increasingly being considered as the initial correction for patients with keratoconus. In this study, keratoconus patients report higher levels of comfort and visual satisfaction with SL compared with corneal gas-permeable lenses (GPs). PURPOSE This study aimed to compare patient satisfaction and care burden associated with GP and SL for the management of keratoconus. METHODS An electronic survey was distributed by the National Keratoconus Foundation from October 2016 to March 2017. Age at diagnosis, initial and current treatment, lens complications, access to care, lens handling time, and annual out-of-pocket treatment costs were collected. Vision, lens comfort, and ease of use satisfaction were rated from 1 to 5. RESULTS A total of 422 responses were received, including 75 bilateral GP and 76 bilateral SL wearers. Scleral lens wearers had greater satisfaction with vision (3.2 ± 1.1 [SL] vs. 2.6 ± 1.1 [GP]; P < .001) and comfort (3.3 ± 1.0 [SL] vs. 2.2 ± 1.2 [GP]; P < .001) but similar ease of use satisfaction in both groups (2.8 ± 1.1 [SL] vs. 2.7 ± 1.1 [GP]; P < .90). Both groups reported issues with cloudy or foggy vision (GP, 63%; SL, 58%) and contact lens discomfort (GP, 77%; SL, 67%). Although GP wearers reported more issues with lens movement or loss (40 [GP] vs. 18% [SL]), they had fewer difficulties with halos (53 vs. 72% [SL]) and lens handling (40%) compared with SL wearers (63%). Gas-permeable lens (48%) and SL (45%) wearers spend 6 to 10 minutes daily handling their lenses. Sixty percent of GP wearers reported annual out-of-pocket cost expenses less than U.S.$1000, whereas only 41% of SL wearers reported the same. CONCLUSIONS Scleral lens wearers with keratoconus report greater satisfaction with vision and comfort than do GP wearers, although both groups reported cloudy vision and lens discomfort.

Purpose: To evaluate the relationship between optic nerve cup-to-disc ratio and peripapillary retinal nerve fiber layer (RNFL) thickness in suspected pediatric glaucoma with large cup-to-disc ratios. Methods: This was a retrospective study undertaken at a single academic institution. Eighty-six eyes of 43 patients who presented with large (≥ 0.5) cup-to-disc ratios in both eyes and without elevated intraocular pressure were evaluated using spectral-domain optical coherence tomography. Global and sectoral peripapillary RNFL thickness measurements, Bruch's membrane opening size, refractive error in spherical equivalents, and intraocular pressure levels were recorded for all patients. Cup-to-disc ratios were manually derived using digital fundus images (D-cup-to-disc ratio). Parameters were compared between gender or race by t tests or analysis of variance. The differences in the relationship among the clinical parameters between two eyes were assessed using generalized estimation equation modeling followed by Pearson's correlation analysis. Results: Forty-three patients (25 boys and 18 girls) with a mean age of 9.3 ± 2.7 years (range: 5 to 15 years) were included. The mean global peripapillary RNFL thickness and the D-cup-to-disc ratio of study eyes were 99.0 ± 9.2 µm and 0.66 ± 0.03, respectively. The peripapillary RNFL thickness was found to be correlated with refractive error ( r = 0.404; P = .008) and Bruch's membrane opening size ( r = 0.410; P = .008) but not with cup-to-disc ratios ( r = 0.029; P = .858) or patient age ( r = −0.044; P = .797). Conclusions: In patients with suspected pediatric glaucoma who present with large cup-to-disc ratios, RNFL thickness does not correlate with the degree of optic nerve cupping. Myopic refractive errors and Bruch's membrane opening size need to be taken into consideration to prevent misinterpretation of peripapillary RNFL measurements. [ J Pediatr Ophthalmol Strabismus . 2020;57(2):90–96.]

Introduction Habitual alcohol consumption and circadian timing are interconnected. Numerous studies have reported that heavy alcohol use is associated with eveningness. Only two studies have assessed the dim light melatonin onset (DLMO) in the context of habitual alcohol use, and both reported a shorter DLMO-midsleep interval was associated with heavier alcohol consumption. A gap in this research is the potential impact of alcohol use on the primary circadian photoreceptor, the intrinsically photosensitive retinal ganglion cells (ipRGCs), which influence circadian timing. This study aimed to compare sleep, circadian timing, and photoreceptor responsivity between light and heavy alcohol drinkers. Methods Participants were healthy (average age 27 years) and included 28 light (average 2.6 drinks/week) and 50 heavy (average 17.9 drinks/week) drinkers. They participated in an 8-day study protocol: 1 week of adlib sleep monitored with wrist actigraphy, followed by a 9-hour laboratory session with a photoreceptor responsivity (post-illumination pupil response, PIPR) and circadian phase assessment. Participants passed a breathalyzer test at the start of the laboratory session. Results Both drinking groups were good sleepers with minimal mood disturbance. Consistent with earlier studies, the heavy drinkers had more eveningness (p=0.029), and a trend for a shorter DLMO-midsleep interval (p=0.059) as compared to the light drinkers. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p=0.006), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. In the light drinkers, a larger PIPR in the evening, reflecting greater sensitivity to phase-delaying light, was significantly associated with a later DLMO (r=0.42, p=0.028). However, this relationship was absent in the heavy drinkers (r=-0.07, p=0.68). Conclusion The findings replicate previous work examining the relationship between chronotype, DLMO, and habitual alcohol consumption. For the first time, circadian photoreceptor responsivity was examined, and found to be significantly reduced in heavy alcohol drinkers as compared to light alcohol drinkers. This finding is consistent with prior rodent studies that found reduced phase shifts to light with acute or chronic alcohol consumption, and suggests that habitual heavy alcohol use may impair the circadian response to light in humans. Support (If Any) Grant awarded from NIAAA R01 AA023839.

The pupil light reflex (PLR) can serve as a biomarker of the photoreceptor function. Protocols for chromatic PLR consider mostly pulsed stimulation. A more sophisticated and promising technique is based on the PLR to flickering stimulation. Our aim was to compare flickering PLR (fPLR) and pulsed PLR (pPLR) parameters to validate the fPLR paradigm. Two different experiments were carried out in young participants to compare parameters of chromatic pupillary measurements under flickering and pulsed conditions. We found that the fPLR amplitude parameter was significantly associated with the pPLR transient constriction parameter. Also, for some conditions, pulse parameters can be identified directly in the fPLR recordings.

Background Cigarette smokers report increases in smoking urge in response to exposure to electronic nicotine delivery systems (ENDS) and dual users, i.e. smokers who also vape ENDS, may exhibit greater cue reactivity than exclusive smokers. The current investigation examined reactivity to a variety of ENDS cues across a large sample of cigarette smokers and dual ENDS users. Methods Young adult smokers (N = 345; > 5 cigarettes per day) were recruited between 2013–2019 for participation in a series of within-subjects laboratory-based studies. Participants completed surveys before and after exposure to a confederate-delivered control cue (water) and an active cue, including cigarette or ENDS cues ranging from first generation “cigalikes” to a fourth generation “pod-mod”. Main outcomes were post-cue changes in desire for combustible cigarettes and e-cigarettes, and smoking behavior as determined by the smoking latency portion of the Smoking Lapse Paradigm after cue exposure. Results Relative to smokers who do not use ENDS, dual users demonstrated higher baseline desire for ENDS and greater ENDS cue reactivity (across product types) in terms of post-cue increases in smoking urge and shorter latency to smoking choice. In contrast, reactivity to the cigarette cue was similar across groups. Conclusions Dual users show heightened ENDS cue reactivity on smoking urge and behavior relative to never users of ENDS, regardless of the type of ENDS cue. Given their reactivity to both cigarette and ENDS cues, it may be difficult for dual users to transition to exclusive vaping or quit tobacco product use altogether.

The aims of this study were to determine if histatin-1 (H1) is present in normal human tears and whether tear levels of H1 varied between normal patients and those with aqueous deficient dry eye disease (ADDE). Patient samples were obtained from 11 normal patients and 11 severe ADDE patients. Relevant patient characteristics, including age, sex, and dry eye disease (DED) diagnostic parameters were collected. Multiple qualitative and quantitative methods were used to compare the concentration of H1 between patient groups. Mixed linear modeling was used to compare H1 levels between groups, and diagnostic performance was assessed using the receiver-operator-characteristic (ROC). ADDE patients had significantly lower H1 concentrations (85.9 ± 63.7 ng/ml) than the normal group (891.6 ± 196.5 ng/ml) (p 13) and Schirmer I (without anesthesia) (

To determine the rate of retinal nerve fiber layer (RNFL) thinning in patients with sickle cell hemoglobinopathies.This was a prospective cohort study.Sixty-seven patients averaging 35.8 ± 11.5 years of age at enrollment with electrophoretically confirmed sickle cell hemoglobinopathies followed by the University of Illinois at Chicago retina clinic for ≥1 year were included. Exclusion criteria included a history of diabetes, uncontrolled hypertension, glaucoma, ocular opacities, other retinopathies, and previous retinal procedures. The optic nerve head RNFL thicknesses were measured with spectral-domain optical coherence tomography (Heidelberg Engineering, Inc) at enrollment and subsequent follow-ups. Linear mixed models were used to estimate rates of thinning.A total of 122 eyes were followed for 3.8 ± 2.0 years (range 1-8 years). Mean global peripapillary RNFL thickness was 100.9 ± 13.0 μm at baseline. Global peripapillary RNFL thickness decreased at a rate of 0.98 μm per year (95% confidence interval [CI] 0.77-1.19 μm/year). A history of stroke was associated with a faster rate of global RNFL thinning (1.72 ± 0.20 vs 0.79 ± 0.12 μm/year, P.001), whereas a history of hypertension was associated with a slower rate of thinning (0.33 ± 0.27 vs 1.14 ± 0.12 μm/year, P = .002).Peripapillary RNFL thinning in patients with sickle cell hemoglobinopathies occurred faster in patients with a history of stroke and slower in patients with controlled hypertension. Future studies will compare these rates to those of healthy age- and race-matched individuals.

RATIONALE: Electronic nicotine delivery systems (ENDS or e-cigarettes) share salient features of combustible smoking, such as inhalation and exhalation behaviors, and evidence indicates that first and second-generation ENDS generalize as smoking cues. The present study examined whether newer, tank-based third-generation ENDS (“mods”) also evoke smoking urges, and whether enhancing the visibility of exhaled aerosol clouds - by increasing the e-liquid vegetable glycerin (VG) content - strengthens the cue salience of ENDS. OBJECTIVES: The objective was to assess the role of exhaled aerosol clouds on ENDS cue potency using a standardized laboratory paradigm designed to mimic real-world exposures METHODS: Using a mixed design, young adult smokers (n=50; mean age 26.5 yrs; ≥5 cigarettes/day) observed a study confederate drinking bottled water (control cue) and vaping an ENDS mod containing e-liquid with either high (73%) or low (0%) VG. Participants completed the Brief Questionnaire on Smoking Urges (BQSU) and visual analog scales (VAS) assessing cigarette and e-cigarette desire pre- and post-cue exposure. RESULTS: Increasing the e-liquid content of VG enhanced the size and visibility of the exhaled aerosol clouds and evoked a greater increase in smoking desire and a more sustained increase in e-cigarette desire relative to the low VG cue. Both cues elicited increases in smoking urges. These results remained after controlling for sex, prior ENDS experience, recent smoking behavior, and menthol preference. CONCLUSIONS: Observation of tank-based ENDS use generalizes as a smoking cue and its cue salience is strengthened by increasing the e-liquid content of VG to enhance the visibility of the exhaled aerosol cloud.

Objectives To assess dry eye symptoms associated with different contact lens modalities in patients with keratoconus using a dry eye questionnaire. Methods An online survey was distributed by the National Keratoconus Foundation. The survey asked participants to report demographic characteristics, current optical correction, age at the time of diagnosis of keratoconus, and contact lens history. The 12-item Ocular Surface Disease Index (OSDI) questionnaire was also completed. Data from participants wearing the same contact lens modality bilaterally were analyzed. Results The survey was completed by 197 individuals wearing the same contact lens modality bilaterally. The average age of participants at the time of the survey was 47.2±14.8 years (range: 15-87 years), and the average age at which keratoconus was diagnosed was 26.1±9.9 years (range: 8-55 years). The mean overall OSDI score of all participants was 40.2±22.8 (range: 0-100). There was no difference in the mean OSDI scores based on current contact lens modality type (F=1.79; n=187; P=0.13). Based on an OSDI score of 33 or higher, 90% of participants reported symptoms indicative of dry eye disease. Scleral lens wearers reported less discomfort on the individual items related to windy and low-humidity conditions. Conclusions Individuals with keratoconus, irrespective of contact lens modality, report a high incidence of dry eye symptoms.

Importance Determination of retinal thinning rates may help to identify patients who are at risk of progression of sickle cell retinopathy. Objective To assess the rates of macular thinning in adults with and without sickle cell retinopathy using spectral-domain optical coherence tomography (OCT) and to identify ocular and systemic risk factors associated with retinal thinning. Design, setting, and participants This longitudinal prospective case-control study enrolled adult participants from a university-based retina subspecialty clinic between February 11, 2009, and July 3, 2019. The study was designed in autumn 2008 and conducted from February 2, 2009, to July 3, 2020. Participants with sickle cell retinopathy (sickle cell group) were matched by age and race with participants without sickle cell retinopathy (control group). Participants received annual spectral-domain OCT and clinical examinations. Those with at least 1 year of follow-up by July 3, 2020, were included in the analysis. Data were analyzed from February 2, 2009, to July 3, 2020. Main outcomes and measures The primary outcome was comparison of spectral-domain OCT measurements from early-treatment diabetic retinopathy study subfield rates of retinal thinning between eyes with and without sickle cell retinopathy and between different sickle cell hemoglobin subtypes. The secondary outcome was identification of ocular and systemic risk factors associated with rates of retinal thinning. Results Among 370 adults (711 eyes) enrolled in the study, 310 participants (606 eyes) had sickle cell retinopathy, and 60 participants (105 eyes) did not. Of those, 175 of 310 participants (56.5%; 344 of 606 eyes [56.8%]; mean [SD] age, 37.8 [12.8] years; 126 women [72.0%]) in the sickle cell group and 31 of 60 participants (51.7%; 46 of 105 eyes [43.8%]; mean [SD] age, 59 [15.4] years; 22 women [71.0%]) in the control group had at least 1 year of clinical and spectral-domain OCT follow-up data from baseline. The mean (SD) follow-up was 53.7 (32.6) months for the sickle cell group and 54.6 (34.9) months for the control group. Rates of macular thinning in the sickle cell group were significantly higher than those in the control group for the inner nasal (difference, -1.18 μm per year; 95% CI, -1.71 to -0.65 μm per year), inner superior (difference, -1.03 μm per year; 95% CI, -1.78 to -0.29 μm per year), inner temporal (difference, -0.61 μm per year; 95% CI, -1.16 to -0.07 μm per year), and outer nasal (difference, -0.41 μm per year; 95% CI, -0.80 to -0.03 μm per year) quadrants. Patients with sickle cell hemoglobin SC and sickle cell hemoglobin β-thalassemia subtypes had higher rates of retinal thinning than those with the sickle cell hemoglobin SS subtype. Risk factors associated with greater rates of retinal thinning included participant age, stage of retinopathy, previous stroke, and presence of hypertension, acute chest syndrome, or diabetes. Hydroxyurea therapy was associated with decreased rates of retinal thinning and may be a protective factor. Conclusions and relevance In this study, rates of retinal thinning were higher among participants with sickle cell retinopathy compared with those without sickle cell retinopathy, and thinning rates increased with participant age and stage of retinopathy. These findings suggest that identifying anatomic worsening of sickle cell maculopathy through spectral-domain OCT may be a useful parameter to evaluate the progression of sickle cell retinopathy.

We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes with and without retinopathy. Those genes exhibiting the largest difference in glucose response were assessed for association with diabetic retinopathy in a genome-wide association study meta-analysis. Expression quantitative trait loci (eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin (FLCN) as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose was greater in individuals with diabetic retinopathy. Independent cohorts of individuals with diabetes revealed an association of FLCN eQTLs with diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy. Integrating genetic association with gene expression implicated FLCN as a disease gene for diabetic retinopathy., eLife digest One of the side effects of diabetes is loss of vision from diabetic retinopathy, which is caused by injury to the light sensing tissue in the eye, the retina. Almost all individuals with diabetes develop diabetic retinopathy to some extent, and it is the leading cause of irreversible vision loss in working-age adults in the United States. How long a person has been living with diabetes, the extent of increased blood sugars and genetics all contribute to the risk and severity of diabetic retinopathy. Unfortunately, virtually no genes associated with diabetic retinopathy have yet been identified. When a gene is activated, it produces messenger molecules known as mRNA that are used by cells as instructions to produce proteins. The analysis of mRNA molecules, as well as genes themselves, can reveal the role of certain genes in disease. The studies of all genes and their associated mRNAs are respectively called genomics and transcriptomics. Genomics reveals what genes are present, while transcriptomics shows how active genes are in different cells. Skol et al. developed methods to study genomics and transcriptomics together to help discover genes that cause diabetic retinopathy. Genes involved in how cells respond to high blood sugar were first identified using cells grown in the lab. By comparing the activity of these genes in people with and without retinopathy the study identified genes associated with an increased risk of retinopathy in diabetes. In people with retinopathy, the activity of the folliculin gene (FLCN) increased more in response to high blood sugar. This was further verified with independent groups of people and using computer models to estimate the effect of different versions of the folliculin gene. The methods used here could be applied to understand complex genetics in other diseases. The results provide new understanding of the effects of diabetes. They may also help in the development of new treatments for diabetic retinopathy, which are likely to improve on the current approach of using laser surgery or injections into the eye.

Scleral lenses (SLs) are increasingly being considered as the initial correction for patients with keratoconus. In this study, keratoconus patients report higher levels of comfort and visual satisfaction with SL compared with corneal gas-permeable lenses (GPs).This study aimed to compare patient satisfaction and care burden associated with GP and SL for the management of keratoconus.An electronic survey was distributed by the National Keratoconus Foundation from October 2016 to March 2017. Age at diagnosis, initial and current treatment, lens complications, access to care, lens handling time, and annual out-of-pocket treatment costs were collected. Vision, lens comfort, and ease of use satisfaction were rated from 1 to 5.A total of 422 responses were received, including 75 bilateral GP and 76 bilateral SL wearers. Scleral lens wearers had greater satisfaction with vision (3.2 ± 1.1 [SL] vs. 2.6 ± 1.1 [GP]; P.001) and comfort (3.3 ± 1.0 [SL] vs. 2.2 ± 1.2 [GP]; P.001) but similar ease of use satisfaction in both groups (2.8 ± 1.1 [SL] vs. 2.7 ± 1.1 [GP]; P.90). Both groups reported issues with cloudy or foggy vision (GP, 63%; SL, 58%) and contact lens discomfort (GP, 77%; SL, 67%). Although GP wearers reported more issues with lens movement or loss (40 [GP] vs. 18% [SL]), they had fewer difficulties with halos (53 vs. 72% [SL]) and lens handling (40%) compared with SL wearers (63%). Gas-permeable lens (48%) and SL (45%) wearers spend 6 to 10 minutes daily handling their lenses. Sixty percent of GP wearers reported annual out-of-pocket cost expenses less than U.S.$1000, whereas only 41% of SL wearers reported the same.Scleral lens wearers with keratoconus report greater satisfaction with vision and comfort than do GP wearers, although both groups reported cloudy vision and lens discomfort.

The goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes (T1D) with and without retinopathy. Those genes exhibiting the largest difference in glucose response between individuals with diabetes with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a genome-wide association study meta-analysis. All genetic variants associated with gene expression (expression Quantitative Trait Loci, eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin (FLCN) as a susceptibility gene for diabetic retinopathy. We show that expression of FLCN in response to glucose was greater in individuals with diabetic retinopathy compared to individuals with diabetes without retinopathy. Three large, independent cohorts of individuals with diabetes revealed an association of FLCN eQTLs to diabetic retinopathy. Mendelian randomization further confirmed a direct positive effect of increased FLCN expression on retinopathy in individuals with diabetes. Together, our studies integrating genetic association and gene expression implicate FLCN as a disease gene for diabetic retinopathy.

Attentional modulation is specific to either luminance or chromatic contrast discrimination, implying separate attentional resources for processing luminance and chromatic information processing [e.g., Curr. Biol. 12, 1134 (2002)CUBLE20960-982210.1016/S0960-9822(02)00921-1]. However, there are two distinct visual pathways that process chromatic information: the parvocellular (PC) and koniocellular (KC) pathways. It is unclear whether there are separate attentional resources modulating the chromatic processes in these pathways. Here, we examined the attentional modulation effects on chromatic contrast discrimination with chromaticities along the l or s cardinal axis on a cone chromaticity space for preferentially stimulating either the inferred PC or KC pathway, respectively. A dual-task interference paradigm was used, and chromatic contrast discrimination sensitivities under dual-task conditions were compared with that under a single-task condition. The results revealed that compared with the single-task condition, attending to a competing central task in the dual-task condition decreased the peripheral discrimination sensitivity in both chromatic cardinal axes, and sensitivity reduced regardless of whether the dual tasks were along the same or different chromatic cardinal axes. These findings indicate that attentional effects on chromatic processes are not specific to the cardinal axis, suggesting that the PC and KC pathways may share a common attention resource in modulating chromatic processing.

Purpose To determine whether 1-year visual and anatomical results after surgery combining pars plana vitrectomy, Boston keratoprosthesis, and a glaucoma drainage device as needed are similar, better, or worse than Boston keratoprosthesis initial implantation alone. Methods We performed a retrospective review of adult patients undergoing Boston keratoprosthesis at our institution. Visual acuity outcomes, anatomical results, and complication rates of patients undergoing combination surgery (including pars plana vitrectomy and a posterior glaucoma drainage device) were compared with those undergoing keratoprosthesis placement alone. Results There were 70 eyes in the keratoprosthesis alone group and 55 eyes in the keratoprosthesis with pars plana vitrectomy group. Mean follow-up durations were 54.67 months in the keratoprosthesis alone group and 48.41 months in the combination group. Baseline mean Snellen equivalent visual acuities were worse for the combination group compared with the keratoprosthesis alone group (P = 0.027). Visual acuities improved postoperatively by 1 month after keratoprosthesis implantation for both groups and improved three or more lines of Snellen acuity in the majority of eyes for both groups (≥72% by 12 months). Eyes undergoing pars plana vitrectomy had lower rates of de novo (P = 0.015) and significantly lower rates of secondary procedures (P = 0.002) at 1 year. One year complications rates for retroprosthetic membrane formation, retinal detachment, hypotony, cystoid macular edema, epiretinal membrane formation, endophthalmitis, and corneal melting were similar for both groups. Conclusion Compared with keratoprosthesis alone, combining keratoprosthesis with pars plana vitrectomy and a glaucoma drainage device as needed, resulted in lower rates of de novo glaucoma, lower rates of additional surgical procedures, similar visual acuity outcomes at 1 year, and did not result in higher complication rates.

BackgroundExposure to the use of first, second and third generations of electronic cigarettes (e-cigarettes) elicits the desire to vape and smoke among observers, as well as facilitates smoking behaviour. Given the rapid rise in the popularity of the pod mod JUUL, we examined whether observing the use of this device would elicit similar responses in smokers. Exploratory analyses were also conducted to determine whether JUUL can act as a smoking cue for former smokers.MethodsThe sample consisted of 82 young adult participants (62 current smokers and 20 former smokers approximately 1 year smoke free). The study examined their response to observing use of bottled water (control cue) and JUUL (active cue) in a controlled laboratory paradigm. Both cues were delivered by a trained study confederate under the guise of a social interaction task, and participants completed mood and desire and urge surveys precue and postcue exposures.ResultsIn current smokers, exposure to the JUUL cue increased smoking urge and desire for a cigarette, mod/vape pen and JUUL, and two-thirds chose to smoke in the behavioural analogue task. In former smokers, the JUUL cue evoked modest and transient increases in desire for a cigarette and JUUL.ConclusionsThe use of JUUL affects the user and elicits responses in observers; this study is the first to demonstrate that exposure to JUUL use may act as a smoking cue and exposure to JUUL use may affect tobacco control efforts.

PURPOSE The Boston keratoprosthesis (KPro) is the most commonly used artificial cornea. It has been proven to be successful for severe corneal disease not amenable to keratoplasty. We have observed our patients reporting debilitating glare despite attaining good visual acuities. This motivated us to objectively measure light scatter in eyes with a KPro. METHODS Light scatter was measured in 21 eyes with the Boston type 1 KPro with a VA of 20/150 or better and was compared with 13 healthy control eyes using the Oculus C-Quant device (Arlington, WA). Eyes were also measured using an occluder contact lens. RESULTS Light scatter (quantified as the logS value) was significantly higher in the KPro group than in the control (2.34 ± 0.15 vs. 1.29 ± 0.17, P < 0.001). The polymethylmethacrylate (PMMA) KPro group (16 eyes, logS 2.49 ± 0.19) but not the titanium group (5 eyes, logS 1.87 ± 0.15) had significantly higher light scattering than the control. The use of an occluder contact lens significantly decreased light scatter in eyes with a PMMA backplate (n = 11, logS 1.71 vs. 2.42, P = 0.028). CONCLUSION This study confirms that intraocular light scatter is increased in KPro eyes. Possibly because of its opaque nature, the titanium backplate model seems to produce less light scatter than does the PMMA model. Occluder contact lenses reduced light scatter significantly in the PMMA KPro and could be a treatment option for symptomatic patients.

Purpose To determine whether the retina is thinner in sickle cell patients than in race- and age-matched controls, and, if it is thinner, whether there is any association with systemic diseases. Methods Sickle cell and control (age- and race-matched) patients were prospectively enrolled from a university retina clinic into this observational study. Participants underwent visual acuity testing, slit-lamp biomicroscopy, dilated ophthalmoscopy, and spectral-domain optical coherence tomography imaging. Sickle cell retinal lesions, degree of vascular tortuosity, caliber of arteriovenous anastomosis, and stage of retinopathy were noted. Early Treatment Diabetic Retinopathy Study (ETDRS) subfield measurements were compared between sickle cell and control subjects and also among sickle cell hemoglobin subtypes. Associations between ETDRS subfield measurements and hemoglobin subtype, retinopathy stage, and systemic diseases were assessed. Results A total of 513 sickle cell eyes (260 patients) and 75 control eyes (39 patients) had median visual acuities of 20/20. ETDRS central ( P = .002), inner (nasal P = .009, superior P = .021, temporal P P = .017), and temporal outer ( P = .012) subfield measurements were thinner in sickle cell eyes compared to control eyes. Hemoglobin SS eyes had significantly thinner inner ETDRS subfield measurements compared to SC and SThal eyes. Retinal thinning in all subfields was associated with age ( P = .017) for sickle cell and control eyes. No association was found between retinal thinning and hydroxyurea use or arteriovenous anastomosis caliber. Conclusions The macula is thinner in sickle cell eyes compared to control eyes; retinal thickness decreases with increasing age and sickle cell retinopathy stage and is most severe in hemoglobin SS subtypes.

Background Binge drinking, defined as consuming five or more standard alcoholic drinks for men (four for women) within a 2-hour period, is common among young adults and is associated with significant alcohol-related morbidity and mortality. To date, most research on this problem in young adults has relied upon retrospective questionnaires or costly laboratory-based procedures. Smartphone-based ecological momentary assessment (EMA) may address these limitations by allowing researchers to measure alcohol use and related consequences in real time and in drinkers’ natural environments. To date, however, relatively less research has systematically examined the utility of this approach in a sample of young adults targeting real-world heavy drinking episodes specifically. Objective This study aimed to evaluate the feasibility, acceptability, and safety of a smartphone-based EMA method targeting binge drinking and related outcomes in heavy drinking young adults during real-world drinking occasions. Methods Young adult binge drinkers in the smartphone group (N=83; mean 25.4 (SD 2.6) years; 58% (48/83) male; bingeing on 23.2% (6.5/28) days in the past month) completed baseline measures of alcohol use and drinking-related consequences, followed by up to two smartphone-based EMA sessions of typical drinking behavior and related outcomes in their natural environments. They also completed next-day and two-week follow-up surveys further assessing alcohol use and related consequences during the EMA sessions and two weeks after study participation, respectively. A separate demographic- and drinking-matched safety comparison group (N=25) completed the baseline and two-week follow-up surveys but did not complete EMA of real-world drinking behavior. Results Most participants (71%, 59/83) in the smartphone group engaged in binge drinking during at least one 3-hour EMA session, consuming 7.3 (SD 3.0) standard alcoholic drinks. They completed 87.2% (507/581) system-initiated EMA prompts during the real-world drinking episode, supporting the feasibility of this approach. The procedure was acceptable, as evidenced by high participant ratings for overall satisfaction with the EMA software and study procedures and low ratings for intrusiveness of the mobile surveys. Regarding safety, participants endorsed few drinking-related consequences during or after the real-world drinking episode, with no adverse or serious adverse events reported. There were no differences between the groups in terms of changes in drinking behavior or consequences from baseline to two-week follow-up. Conclusions This study provided preliminary support for the feasibility, acceptability, and safety of a smartphone-based EMA of real-time alcohol use and related outcomes in young adult heavy drinkers. The results suggest that young adults can use smartphones to safely monitor drinking even during very heavy drinking episodes. Smartphone-based EMA has strong potential to inform future research on the epidemiology of and intervention for alcohol use disorder by providing researchers with an efficient and inexpensive way to capture large amounts of data on real-world drinking behavior and consequences.

The intrinsic melanopsin photoresponse may initiate visual signals that differ in spatiotemporal characteristics from the cone-opsin- and rhodopsin-mediated signals. Applying the CIE standard observer functions in silent-substitution methods can require individual differences in photoreceptor spectral sensitivities and pre-receptoral filtering to be corrected; failure to do so can lead to the intrusion of more sensitive cone processes with putative melanopsin-directed stimuli. Here we evaluate heterochromatic flicker photometry (HFP) and photoreceptor-directed temporal white noise as techniques to limit the effect of these individual differences. Individualized luminous efficiency functions ( V ( λ ) ) were compared to the CIE standard observer functions. We show that adapting chromaticities used in silent-substitution methods can deviate by up to 54% in luminance when estimated with the individual and standard observer functions. These deviations lead to inadvertent cone intrusions in the visual functions measured with melanopsin-directed stimuli. To eliminate the intrusions, individual HFP corrections are sufficient at low frequencies ( ∼ 1 H z ) but temporal white noise is also required at higher frequencies to desensitize penumbral cones. We therefore recommend the selective application of individualized observer calibration and/or temporal white noise in silent-substitution paradigms when studying melanopsin-directed photoresponses.

The theory of behavioral tolerance to alcohol posits that greater experience with drinking to intoxication leads to less impaired cognitive and psychomotor performance. However, the degree to which behavioral tolerance develops or changes over time in adults due to repeated heavy alcohol drinking has not been clearly demonstrated. We examined data from the first 6 years of the Chicago Social Drinking Project to test whether chronic heavy drinkers (HDs; n = 86) and light drinkers (LDs; n = 69) exhibit behavioral tolerance or changes in perceived impairment at two testing phases in early adulthood. Tasks were the Grooved Pegboard and Digit Symbol Substitution Test (DSST) given at initial testing and then repeated in a re-examination phase 5 years later. Alcohol (0.8 g/kg) and placebo were administered at separate sessions in each phase for a total of 620 individual laboratory sessions. HDs exhibited less impairment over time on the Pegboard task but not on the DSST, while LDs did not exhibit behavioral tolerance on either task. HDs reported persistently lower perceived impairment compared to LDs. These findings demonstrate that behavioral tolerance in HDs is evident over time on rote fine motor skills (Pegboard) but not more complex skills integrating motor speed, encoding, and short-term memory (DSST). The results have implications for our understanding of alcohol-induced impairments across neurobehavioral processes in heavy drinkers and their ongoing risks for alcohol-related consequences over time.

Purpose: To report indications and outcomes of combined pars plana vitrectomy and penetrating keratoplasty (PPV-PKP). Methods: A review of all patients who underwent PPV-PKP at the Illinois Eye and Ear Infirmary from January 1, 2001 to May 31, 2013, was performed. Ninety eyes of 90 patients were identified. Survival analysis was utilized to assess differences in retinal detachment (RD) and corneal graft failure rates among groups based on clinical and surgical variables. Results: Seventy-nine eyes met the inclusion criteria. Most common indications for vitrectomy and corneal transplantation were RD (65%) and corneal decompensation (43%), respectively. The preoperative and final visual acuity (VA) logarithm of the minimum angle of resolution values were 2.7 (0.31) and 2.5 (0.67) (hand motions; mean [SD]; P = .02); 15% of eyes were ≥20/400 and 15% gained ≥2 lines of vision following surgery. Corneal graft failure occurred in 51% (40 eyes), recurrent RD in 28% (22 eyes), and hypotony in 25% (20 eyes). Silicone oil endotamponade was associated with postoperative RD ( P = .045), and previous ocular trauma was associated with postoperative corneal graft failure ( P = .023). Conclusion: Combined PPV-PKP surgery was likely to achieve stabilization of VA, with a minority of eyes achieving modest gains in VA.

Introduction Passive exposure to the use of electronic nicotine delivery systems (ENDS or e-cigarettes) has been shown to generalize as a smoking cue. As young adult women in particular are increasingly targeted by ENDS distributors, the present study examined whether passive exposure to the use of a female-marketed ENDS product selectively enhanced smoking urge, cigarette and e-cigarette desire, and smoking behavior among women (vs men) smokers. Methods Using a mixed design, young adult smokers (n = 64; mean age 28.2 yrs.; ≥5 cigarettes/day) observed a study confederate drink bottled water (control cue) and then vape a female-marketed tank-based ENDS (active cue). Main measures were the Brief Questionnaire of Smoking Urges (BQSU) and visual analog scales (VAS) for cigarette and e-cigarette desire pre- and post-cue exposure, followed by a smoking latency task. Results Compared to the control cue, the female-marketed ENDS cue increased smoking urge and desire for cigarettes and e-cigarettes to a similar extent in women and men. It also affected subsequent smoking behavior similarly between the sexes, with 68% of men and 58% of women opting to smoke (vs. obtaining monetary reinforcers). Conclusions Both women and men were sensitive to the use of the female-marketed ENDS as a smoking cue. Consistent with prior work by our group, findings demonstrate the cue salience of ENDS, which may be attributable to the aspects of vaping that resemble traditional smoking (e.g. hand-to-mouth and inhalation and exhalation behaviors).

BACKGROUND Binge drinking, defined as consuming five or more standard alcoholic drinks for men (four for women) within a 2-hour period, is common among young adults and is associated with significant alcohol-related morbidity and mortality. To date, most research on this problem in young adults has relied upon retrospective questionnaires or costly laboratory-based procedures. Smartphone-based ecological momentary assessment (EMA) may address these limitations by allowing researchers to measure alcohol use and related consequences in real time and in drinkers’ natural environments. To date, however, relatively less research has systematically examined the utility of this approach in a sample of young adults targeting real-world heavy drinking episodes specifically. OBJECTIVE This study aimed to evaluate the feasibility, acceptability, and safety of a smartphone-based EMA method targeting binge drinking and related outcomes in heavy drinking young adults during real-world drinking occasions. METHODS Young adult binge drinkers in the smartphone group (N=83; mean 25.4 (SD 2.6) years; 58% (48/83) male; bingeing on 23.2% (6.5/28) days in the past month) completed baseline measures of alcohol use and drinking-related consequences, followed by up to two smartphone-based EMA sessions of typical drinking behavior and related outcomes in their natural environments. They also completed next-day and two-week follow-up surveys further assessing alcohol use and related consequences during the EMA sessions and two weeks after study participation, respectively. A separate demographic- and drinking-matched safety comparison group (N=25) completed the baseline and two-week follow-up surveys but did not complete EMA of real-world drinking behavior. RESULTS Most participants (71%, 59/83) in the smartphone group engaged in binge drinking during at least one 3-hour EMA session, consuming 7.3 (SD 3.0) standard alcoholic drinks. They completed 87.2% (507/581) system-initiated EMA prompts during the real-world drinking episode, supporting the feasibility of this approach. The procedure was acceptable, as evidenced by high participant ratings for overall satisfaction with the EMA software and study procedures and low ratings for intrusiveness of the mobile surveys. Regarding safety, participants endorsed few drinking-related consequences during or after the real-world drinking episode, with no adverse or serious adverse events reported. There were no differences between the groups in terms of changes in drinking behavior or consequences from baseline to two-week follow-up. CONCLUSIONS This study provided preliminary support for the feasibility, acceptability, and safety of a smartphone-based EMA of real-time alcohol use and related outcomes in young adult heavy drinkers. The results suggest that young adults can use smartphones to safely monitor drinking even during very heavy drinking episodes. Smartphone-based EMA has strong potential to inform future research on the epidemiology of and intervention for alcohol use disorder by providing researchers with an efficient and inexpensive way to capture large amounts of data on real-world drinking behavior and consequences.

The precise control of visual sensitivity to variations in external lighting is critical for optimising human visual function in a changing environment. In photopic illumination, the cone photoreceptors and their post-receptoral pathways have a primary role in regulating these adjustments; it is not fully understood how a small population of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) can interact with the three cone photoreceptor classes to modulate human visual function. Here we investigated interactions between these inner and outer retinal photoreceptor classes in participants with trichromatic colour vision under conditions that independently controlled the excitations of ipRGCs, cones and rods in the retina. In the peripheral retina, we show that interaction between melanopsin- and cone-directed signals affect conscious, image-forming vision. The interaction patterns are inconsistent with any potential effects arising from artefacts due to open-field and penumbral-cone contrasts, or rod intrusion. For cone signals mediated via each of the three primary visual pathways, melanopsin activation enhances contrast sensitivity. The contrast response functions indicate this enhancement is a more generalised facilitation effect that onsets at ∼9% melanopsin contrast. The implication for human vision is that the contrast sensitivity of cone-mediated visual processes can be modulated by the level of melanopsin excitation in the stimulus light.

The white noise electroretinogram (wnERG) provides a measure of the impulse response function under conditions of retinal equilibrium; it is yet to be determined how the electrical response generated by melanopsin ganglion cell photoreception is expressed in the impulse response. To this end, we recorded the human wnERG to continuous temporal white noise (TWN) stimuli that were melanopsin-directed (rod and cone silent) or cone-directed (rod and melanopsin silent). The impulse response of the electroretinogram was derived by cross-correlating the TWN stimulus with the wnERG response. We observed that the LMS-cone directed wnERG contained the expected N1 wave (24.1 ± 2.4 ms; mean ± SEM) and P1 wave (49.7 ± 1.8 ms). Melanopsin-directed stimuli produced a unique wnERG with a slower negative deflection (Nm) at 62.9 ± 3.3 ms followed by a positive deflection (Pm) at 126.3 ± 5.1 ms. Additional experiments indicated this melanopsin-directed wnERG response was not due to cone intrusion. The Nm and NmPm amplitudes increased with illuminance (32,000–80,000 Td; no rod intrusion) and melanopsin contrast (10–36% Michelson contrast). As there are known pathways connecting melanopsin cells to the outer retina, we then measured the wnERG to combined melanopsin and cone-directed stimuli to quantify melanopsin interactions with cone signalling. With the combined stimuli, the N1P1 amplitudes were suppressed by ~59%, which may be a result of a destructive interference between the positive (P1) and negative (Nm) waves generated by the cone and melanopsin pathways. We conclude that the human wnERG to melanopsin-directed stimuli may reflect the combined response of intra-retinal melanopsin pathways, independent of rod and cone photoreception.

Use and awareness of electronic nicotine delivery systems (ENDS; also known as electronic cigarettes or e-cigarettes) has increased rapidly in recent years, particularly among young adults. As use of ENDS resembles traditional smoking in both hand to mouth movements and inhalation and exhalation behaviors, we determined whether exposure to e-cigarette use via video exposure would act as a cue to elicit urge and desire for a combustible cigarette. Young adult smokers (mean age 26.3 ± 4.1 years) were randomized to view a brief video montage of advertisements depicting either e-cigarette vaping (n = 38) or bottled water drinking (n = 40). Pre- and post-cue exposure assessments were conducted in a controlled laboratory setting without other smoking or vaping cues present or behaviors allowed. Primary outcomes included change from pre-exposure baseline in smoking urge (Brief Questionnaire of Smoking Urges) and desire for a combustible and e-cigarette (visual analogue scales). Results showed that relative to exposure to the bottled water video, exposure to the ENDS video significantly increased smoking urge (p < 0.001) as well as desire for a regular cigarette (p < 0.05) and an e-cigarette (p < 0.001). These findings provide preliminary evidence that passive exposure to video imagery of ENDS use may generalize as a condition cue and evoke urges for a combustible cigarette in young adult smokers. It remains to be determined whether such increases in urge and desire correspond to increases in actual smoking behavior.