Drinking context, alcohol use, and subjective responses during binge drinking episodes measured by high-resolution ecological momentary assessment (HR-EMA).

OBJECTIVE: 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. METHOD: Young adult heavy drinkers (N = 61; 57% male) completed two smartphone-based, 3-hr HR-EMA of drinking context (social context and location), alcohol use, and subjective responses (alcohol stimulation, sedation, feeling, liking, and wanting more). Analyses examined the associations between drinking context and subjective alcohol responses, accounting for demographic characteristics and individual differences in alcohol consumption. RESULTS: 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. CONCLUSIONS: 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) 2023 APA, all rights reserved).

Scleral lens prescription and management practices: Emerging consensus.

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.

Is melanopsin activation affecting large field color-matching functions?

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.

Temporal integration of rod signals in luminance and chromatic pathways.

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.

Comparing flickering and pulsed chromatic pupil light responses.

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.

Sleep and circadian differences between light and heavy adult alcohol drinkers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Haven't lost the positive feeling: a dose-response, oral alcohol challenge study in drinkers with alcohol use disorder.

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.

Effect of Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Among Smokers Who Drink Heavily: A Randomized Clinical Trial.

IMPORTANCE: 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. OBJECTIVE: To determine whether combined treatment with varenicline tartrate and nicotine patch improves continuous abstinence from cigarette smoking among smokers who drink heavily. DESIGN, SETTING, AND PARTICIPANTS: 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 or >7 drinks per week for women and ≥1 heavy drinking day [defined as >5 drinks per occasion for men or >4 drinks per occasion for women] per month for the past year) and had a desire to quit smoking. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02859142.

Refractive Outcomes for Combined Phacoemulsification and Glaucoma Drainage Procedure.

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.

Dynamics of Visual Adaptation With Simultaneous Stimulation of Two Visual Pathways.

Primates' retinal ganglion cells in different visual pathways have been shown to adapt independently (Current Biology 22 (2012) 220-224). However, the manner in which adaptation occurs under simultaneous stimulation of two visual pathways has not yet been explored. In this study, the dynamics of color afterimages were measured while stimulating one or two visual pathway using a time-varying afterimage paradigm. The dynamics of adaptation was approximately equivalent among the three primary visual pathways, but adaptation was slower for simultaneous stimulation of two visual pathways compared to the stimulation of one visual pathway. In addition, we found that the speed of adaptation also depends upon which two pathways are combined. We developed a two-stage adaptation model, both with the same dynamics, to account for the results with simultaneous stimulation of two pathways.

Dry Eye Symptoms in Individuals With Keratoconus Wearing Contact Lenses.

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.

Electronic nicotine delivery systems (ENDS) cue reactivity in dual users: A combined analysis.

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.

Optimizing methods to isolate melanopsin-directed responses.

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 (∼1Hz) 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.

Visual Outcomes in Pediatric Patients with Peters Anomaly.

PURPOSE: 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.

Alcohol subjective responses in heavy drinkers: Measuring acute effects in the natural environment versus the controlled laboratory setting.

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.

Longitudinal Assessment of Retinal Thinning in Adults With and Without Sickle Cell Retinopathy Using Spectral-Domain Optical Coherence Tomography.

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 ß-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.

Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder.

OBJECTIVE: Alcohol use disorder (AUD) remains an urgent public health problem. Longitudinal data are needed to clarify the role of acute subjective responses to alcohol in the development and maintenance of excessive drinking and AUD. The authors report on 10 years of repeated examination of acute alcohol responses in the Chicago Social Drinking Project. METHODS: Young adult drinkers (N=190) participated in an initial alcohol challenge (0.8 g/kg of alcohol compared with placebo) that was repeated 5 and 10 years later. They were also assessed on drinking behavior and AUD symptoms at numerous intervals across the decade. Retention was high, as 184 of the 185 (99%) nondeceased active participants completed the 10-year follow-up, and 91% (163 of 179) of those eligible for alcohol consumption engaged in repeated laboratory testing during this interval. RESULTS: At the end of the decade, 21% of participants met criteria for past-year AUD. Individuals who reported the greatest alcohol stimulation, liking, and wanting at the initial alcohol challenge were most likely to have developed AUD 10 years later. Further, alcohol-induced stimulation and wanting increased in reexamination testing among those with the highest AUD symptoms as the decade progressed. CONCLUSIONS: Initial stimulant and rewarding effects of alcohol predicted heavy alcohol use, and the magnitude of these positive subjective effects increased over a 10-year period in those who developed AUD compared with those who did not develop the disorder. The findings demonstrate systematic changes in subjective responses to alcohol over time, providing an empirical basis for prevention, early intervention, and treatment strategies.

Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.

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.

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.

The Feasibility, Tolerability, and Safety of Administering a Very High Alcohol Dose to Drinkers with Alcohol Use Disorder.

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 to 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 3 laboratory sessions at which they consumed a beverage with 1.2, 0.8, 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 presession alcohol abstinence requirements (indicated by BrAC < 0.003 g/dl), with no participants exhibiting serious alcohol withdrawal symptoms at arrival to study visits. The 1.2 g/kg alcohol dose achieved an expected mean peak BrAC of 0.13 g/dl at 60 minutes after drinking, which was well tolerated; the majority of the sample did not experience nausea (70%) or vomiting (93%), and dose effects on vital signs were not clinically significant. Finally, we demonstrated that the 1.2 g/kg alcohol dose is safe and not associated with postsession consequences, including reduced sleep time, atypical substance use, accidents or injuries, and severe hangovers. CONCLUSION: Results support the feasibility, tolerability, and safety of administering a very high alcohol dose to young adult drinkers with AUD within the context of a well-validated laboratory alcohol challenge paradigm. Utilizing an alcohol dose more consistent with naturalistic drinking patterns may foster greater ecological validity of laboratory paradigms for persons with moderate to severe AUD.

Keratoconus Patient Satisfaction and Care Burden with Corneal Gas-permeable and Scleral Lenses.

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.