Anthropogenic climate change is worsening North American pollen seasons.

Airborne pollen has major respiratory health impacts and anthropogenic climate change may increase pollen concentrations and extend pollen seasons. While greenhouse and field studies indicate that pollen concentrations are correlated with temperature, a formal detection and attribution of the role of anthropogenic climate change in continental pollen seasons is urgently needed. Here, we use long-term pollen data from 60 North American stations from 1990 to 2018, spanning 821 site-years of data, and Earth system model simulations to quantify the role of human-caused climate change in continental patterns in pollen concentrations. We find widespread advances and lengthening of pollen seasons (+20 d) and increases in pollen concentrations (+21%) across North America, which are strongly coupled to observed warming. Human forcing of the climate system contributed ∼50% (interquartile range: 19-84%) of the trend in pollen seasons and ∼8% (4-14%) of the trend in pollen concentrations. Our results reveal that anthropogenic climate change has already exacerbated pollen seasons in the past three decades with attendant deleterious effects on respiratory health.

Higher airborne pollen concentrations correlated with increased SARS-CoV-2 infection rates, as evidenced from 31 countries across the globe.

Pollen exposure weakens the immunity against certain seasonal respiratory viruses by diminishing the antiviral interferon response. Here we investigate whether the same applies to the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is sensitive to antiviral interferons, if infection waves coincide with high airborne pollen concentrations. Our original hypothesis was that more airborne pollen would lead to increases in infection rates. To examine this, we performed a cross-sectional and longitudinal data analysis on SARS-CoV-2 infection, airborne pollen, and meteorological factors. Our dataset is the most comprehensive, largest possible worldwide from 130 stations, across 31 countries and five continents. To explicitly investigate the effects of social contact, we additionally considered population density of each study area, as well as lockdown effects, in all possible combinations: without any lockdown, with mixed lockdown-no lockdown regime, and under complete lockdown. We found that airborne pollen, sometimes in synergy with humidity and temperature, explained, on average, 44% of the infection rate variability. Infection rates increased after higher pollen concentrations most frequently during the four previous days. Without lockdown, an increase of pollen abundance by 100 pollen/m3 resulted in a 4% average increase of infection rates. Lockdown halved infection rates under similar pollen concentrations. As there can be no preventive measures against airborne pollen exposure, we suggest wide dissemination of pollen-virus coexposure dire effect information to encourage high-risk individuals to wear particle filter masks during high springtime pollen concentrations.

The influence of sea breeze on mold spore dispersion.

Background: Many allergists consider the ocean breeze to be free of allergens and recommend visits to the coast for relief; however, the coast may perpetuate an allergenic environment. Objective: This study investigated the sea breeze's impact on spore dispersion between coastal and inland sites, and the potential implications of sea breeze on human health and coastal resources. Methods: Spore sampling occurred during 2006 by using pollen samplers. Samplers were located at the Rutgers University Institute of Marine and Coastal Sciences Marine Field Station and the Rutgers University Pinelands Field Station. Statistical analysis was performed on the spore data to compare concentrations from the various locations. The effect of sea breeze circulation on particulate matter was analyzed from meteorological data collected in 2006. Sea breeze data were collected from simulations, Doppler radar, and meteorological towers at varying heights. Results: There was no significant difference between the total spore concentration at the New Jersey coast and the New Jersey Pinelands canopy. Conclusion: Sea breeze has been shown to favor aerobiologic transfers from coastal seawater to land, but the immediate environment (floor) still remains a primary determinant of affecting an individual's allergic airway disease. Results of some studies have shown that coastal environments may favor the onset allergic airway, but in our study this seemed to be equivalent to the floor (or immediate locale) of an individual affected with allergy. However, the sea breeze effect seemed to have the ability to impact allergic airway disease (AAD) populations not only living along the coasts but of those living up to 130 km inland and potentially those living in the Philadelphia metropolitan area.

Ocular symptoms improvement from intranasal triamcinolone compared with placebo and intranasal fluticasone propionate: A meta-analysis.

BACKGROUND: Allergic rhinitis is a prevalent disease, which can be classed as seasonal (SAR) or perennial. In addition to nasal symptoms, up to 75% of sufferers experience itching, redness, and tearing of the eyes. Intranasal corticosteroids are effective in controlling the allergic nasal symptoms, and increasing evidence suggests that they also can relieve some of the allergic ocular symptoms. OBJECTIVE: To evaluate the magnitude of efficacy of triamcinolone acetonide (TAA) compared with placebo or fluticasone propionate (FP) on ocular symptom improvement in patients with SAR. METHODS: A meta-analysis of summary data from 8 randomized, double- or single-blind trials, assessing mean change in total or individual (tearing, redness, and itching) eye symptoms was conducted. Trials that administered a daily dose of 220 µg TAA vs placebo or 200 µg FP over at least 2 weeks' duration, in patients aged 12 years or older with SAR, were analyzed. RESULTS: Total eye symptom reduction after 2 weeks was greater with TAA than placebo, with a mean treatment difference of -0.32 (95% CI, -0.444 to -0.203). In addition, significant reductions in tearing, but not itching or redness, were observed after TAA treatment compared with placebo. No significant treatment difference was seen between TAA and FP in total ocular symptoms at any of the time points measured (weeks 1, 2, 3, and overall). All treatments exhibited similar safety profiles and were deemed well tolerated. CONCLUSION: The meta-analysis demonstrated the positive clinical improvements TAA has on total ocular allergy symptoms, especially tearing, in addition to its recognized nasal symptom efficacy in SAR.

ICON: Diagnosis and management of allergic conjunctivitis.

Ocular allergy (OA), interchangeably known as allergic conjunctivitis, is a common immunological hypersensitivity disorder affecting up to 40% of the population. Ocular allergy has been increasing in frequency, with symptoms of itching, redness, and swelling that significantly impacts an individual's quality of life (QOL). Ocular allergy is an often underdiagnosed and undertreated health problem, because only 10% of patients with OA symptoms seek medical attention, whereas most patients manage with over-the-counter medications and complementary nonpharmacological remedies. The clinical course, duration, severity, and co-morbidities are varied and depend, in part, on the specific ocular tissues that are affected and on immunologic mechanism(s) involved, both local and systemic. It is frequently associated with allergic rhinitis (commonly recognized as allergic rhino conjunctivitis), and with other allergic comorbidities. The predominance of self-management increases the risk of suboptimal therapy that leads to recurrent exacerbations and the potential for development of more chronic conditions that can lead to corneal complications and interference with the visual axis. Multiple, often co-existing causes are seen, and a broad differential diagnosis for OA, increasing the difficulty of arriving at the correct diagnosis(es). Ocular allergy commonly overlaps with other anterior ocular disease disorders, including infectious disorders and dry eye syndromes. Therefore, successful management includes overcoming the challenges of underdiagnosis and even misdiagnosis by a better understanding of the subtleties of an in-depth patient history, ophthalmologic examination techniques, and diagnostic procedures, which are of paramount importance in making an accurate diagnosis of OA. Appropriate cross-referral between specialists (allergists and eyecare specialists) would maximize patient care and outcomes. This would significantly improve OA management and overcome the unmet needs in global health.

Allergic inflammation of the anterior surface of the eye.

Background: Ocular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis and includes tear film dysfunction. With the current advent of both repurposed drugs for ocular allergies, as well as novel drugs, lubricants and methods of administration, there is a need to update new treatments to optimize the care of ocular allergy patients. Methods: An overview of mediators, clinical characteristics and management is provided in a summary format. Results: Lubricants (best when refrigerated provide immediate relief that is short lived (several minutes) due to its dilutional effect on mediators and pollen in the tear film. Immediate and longer-term benefit occurs from different topical and oral medications - primarily histamine receptor agonists. Conclusion: The newest prescription topical ophthalmic histamine H1 receptor antagonist (an inverse agonist) to be approved by the U.S. Food and Drug Administration in the past 10 years (U.S. NDA approved May 30, 2017) is cetirizine ophthalmic solution for the treatment of ocular itching with allergic conjunctivitis in adults and in children more than 2 years old.

Emerging Therapeutics for Ocular Surface Disease.

PURPOSE OF REVIEW: The purpose of this article is to review treatment advances in ocular allergy that include the treatment of the various signs and symptoms of the allergic inflammatory response of the ocular surface. RECENT FINDINGS: Recent studies have demonstrated improved pharmacological effect of topical agents with artificial tears and cold compresses; brimonidine, a new ophthalmic decongestant which has demonstrated decreased rebound conjunctivitis; and potential use of contact lens and other novel delivery instruments to increase medication retention time. Currently, there have been limited advances in novel ophthalmic treatments. Non-pharmacological interventions have demonstrated in a randomized control study that artificial tears and the use cold compresses alone or in combination with ophthalmic antihistamines can enhance the effectiveness of a traditional pharmacological therapy. The primary advances have been the start of head-to-head studies comparing various agents actively being used in the treatment of ocular allergy. In addition, there has been increasing interest in the development of novel delivery systems to increase residence time of pharmacological agents in the ocular surface such as nanoparticles, microfilms; examining novel pathways of controlling the allergic inflammatory response of the ocular surface such as modulation of cytokines, transcription factors, and immunophilins.

Asthma, oculonasal symptoms, and skin test sensitivity across National Health and Nutrition Examination Surveys.

BACKGROUND: The increasing prevalence of allergies and asthma has been reported. However, the progression of the prevalence of allergy (the "allergic diathesis progression") has not been examined over time from skin test positivity to oculonasal symptoms to the development of asthma. OBJECTIVE: To investigate the change in the prevalences and associations of positive skin test reactions, oculonasal symptoms, and asthma during the Second and Third National Health and Nutrition Examination Surveys (NHANES II and NHANES III, respectively). METHODS: Data collected during NHANES II and III were used. The prevalence and associations of positive skin test reactions, oculonasal symptoms, and asthma and the linear trend of oculonasal symptoms and asthma prevalence across different cumulative positive skin test reactions were calculated for each NHANES period. RESULTS: From NHANES II to NHANES III, the prevalence of asthma doubled (2 times) and increased for positive skin test reactions (2.2 times), oculonasal symptoms (3.3 times), and concurrence of asthma, oculonasal symptoms, and positive skin test reactions (5.3 times). People were sensitive to an increasing number of allergens. Positive skin test reactions increased from 0.2% (NHANES II) to 2.7% (NHANES III) for people allergic to all 6 allergens. CONCLUSION: Despite some methodologic differences in skin tests across NHANES II and III, this study demonstrated significant increases in allergen sensitivities (prevalence and number of allergens), oculonasal symptoms, and asthma over a 20-year course, indicating that increased sensitivity led to increased allergic symptoms and asthma during the 20 years from NHANES II to NHANES III.

Penicillin skin testing in hospitalized patients with ß-lactam allergies: Effect on antibiotic selection and cost.

BACKGROUND: A history of a penicillin allergy generally leads to the use of broad-spectrum antibiotics that may increase complications and cost. OBJECTIVE: To determine the cost-effectiveness of performing penicillin skin testing (PST). METHODS: A retrospective analysis was conducted on adult inpatients with a ß-lactam allergy who underwent PST and oral challenge performed by an allergist. The primary outcome was overall antibiotic cost savings for patients switched to a ß-lactam antibiotic (BLA). Secondary outcomes included subsequent admissions that required antibiotics and total number of days a BLA was prescribed. RESULTS: Fifty patients had PST performed (mean age, 62 years). The most common ß-lactam allergy reported was penicillin (92%). Cutaneous reactions were reported in 54% of patients, and 56% had a reaction more than 20 years ago. Fifty percent of patients had aztreonam prescribed before PST. The results of PST were negative in all patients, and 1 patient had anaphylactic symptoms during the oral amoxicillin challenge (98% skin test or oral challenge negative). Thirty-seven patients (75.5%) were changed to a BLA. Overall cost savings were $11,005 ($297 per patient switched to a BLA). There were 31 subsequent admissions that required antibiotics for patients who tested negative on skin test and oral challenge. A BLA was prescribed in 22 of 31 readmissions, totaling 147 days of BLA therapy. CONCLUSION: After the implementation of a PST protocol, we observed a decrease in non-BLA use in patients with previously documented ß-lactam allergy. PST is a safe and cost-effective procedure to serve as a negative predictor test for penicillin hypersensitivity mediated by IgE.

Allergenic pollen season variations in the past two decades under changing climate in the United States.

Many diseases are linked with climate trends and variations. In particular, climate change is expected to alter the spatiotemporal dynamics of allergenic airborne pollen and potentially increase occurrence of allergic airway disease. Understanding the spatiotemporal patterns of changes in pollen season timing and levels is thus important in assessing climate impacts on aerobiology and allergy caused by allergenic airborne pollen. Here, we describe the spatiotemporal patterns of changes in the seasonal timing and levels of allergenic airborne pollen for multiple taxa in different climate regions at a continental scale. The allergenic pollen seasons of representative trees, weeds and grass during the past decade (2001-2010) across the contiguous United States have been observed to start 3.0 [95% Confidence Interval (CI), 1.1-4.9] days earlier on average than in the 1990s (1994-2000). The average peak value and annual total of daily counted airborne pollen have increased by 42.4% (95% CI, 21.9-62.9%) and 46.0% (95% CI, 21.5-70.5%), respectively. Changes of pollen season timing and airborne levels depend on latitude, and are associated with changes of growing degree days, frost free days, and precipitation. These changes are likely due to recent climate change and particularly the enhanced warming and precipitation at higher latitudes in the contiguous United States.

Predicting Onset and Duration of Airborne Allergenic Pollen Season in the United States.

Allergenic pollen is one of the main triggers of Allergic Airway Disease (AAD) affecting 5% to 30% of the population in industrialized countries. A modeling framework has been developed using correlation and collinearity analyses, simulated annealing, and stepwise regression based on nationwide observations of airborne pollen counts and climatic factors to predict the onsets and durations of allergenic pollen seasons of representative trees, weeds and grass in the contiguous United States. Main factors considered are monthly, seasonal and annual mean temperatures and accumulative precipitations, latitude, elevation, Growing Degree Day (GDD), Frost Free Day (FFD), Start Date (SD) and Season Length (SL) in the previous year. The estimated mean SD and SL for birch (Betula), oak (Quercus), ragweed (Ambrosia), mugwort (Artemisia) and grass (Poaceae) pollen season in 1994-2010 are mostly within 0 to 6 days of the corresponding observations for the majority of the National Allergy Bureau (NAB) monitoring stations across the contiguous US. The simulated spatially resolved maps for onset and duration of allergenic pollen season in the contiguous US are consistent with the long term observations.

Diagnosis and treatment of nasal and ocular allergies: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.

BACKGROUND: Allergic rhinoconjunctivitis (ARC) is managed by a number of health care professional specialties, whose practice styles may vary. OBJECTIVE: To survey patients and health care professionals about the diagnosis and treatment of ARC. METHODS: The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys were telephone surveys of randomly selected patients and health care professionals in the United States in 2012. Participants were 2,765 people ever diagnosed as having nasal and/or ocular allergies and 500 practitioners in 7 specialties who were treating ARC. RESULTS: Adult respondents to the patient survey reported that their allergies had been diagnosed most often by physicians in family practice (46%) rather than by allergists/immunologists (17%) or otolaryngologists (11%). Children's allergies had been diagnosed most often by pediatricians (41%) and family practitioners (22%). Most respondents with conditions diagnosed by an allergist/immunologist (94.9%) or otolaryngologist (62.7%) had been given an allergy test, but the test was not given to most patients with conditions diagnosed by family practitioners (61.3%) or pediatricians (64.9%). Most patients (75.8%) were treating their allergies with over-the-counter medications, and 53.5% were taking prescription medications. Allergen immunotherapy was being used by 33% (adult) or 28% (child) patients of allergist/immunologists, 25% (adult) or 24% (child) patients of otolaryngologists, and 8% and 10% of patients of family practitioners and pediatricians, respectively. CONCLUSION: Most patients took nonprescription medications for their allergy symptoms or were treated by general practitioners, who did not use allergy testing when diagnosing ARC. Most patients seen by allergist/immunologists and otolaryngologists were evaluated with allergy tests, and most allergen immunotherapy was provided by allergy specialists.

Associations between ozone, PM2.5, and four pollen types on emergency department pediatric asthma events during the warm season in New Jersey: a case-crossover study.

BACKGROUND: Asthma is one of the most common chronic diseases among school-aged children in the United States. Environmental respiratory irritants exacerbate asthma among children. Understanding the impact of a variety of known and biologically plausible environmental irritants and triggers among children in New Jersey - ozone, fine particulate matter (PM2.5), tree pollen, weed pollen, grass pollen and ragweed - would allow for informed public health interventions. METHODS: Time-stratified case-crossover design was used to study the transient impact of ozone, PM2.5 and pollen on the acute onset of pediatric asthma. Daily emergency department visits were obtained for children aged 3-17 years with a primary diagnosis of asthma during the warm season (April through September), 2004-2007 (inclusive). Bi-directional control sampling was used to select two control periods for each case for a total of 65,562 inclusion days. Since the period of exposure prior to emergency department visit may be the most clinically relevant, lag exposures were investigated (same day (lag0), 1, 2, 3, 4, and 5 as well as 3-day and 5-day moving averages). Multivariable conditional logistic regression controlling for holiday, school-in-session indicator, and 3-day moving average for temperature and relative humidity was used to examine the associations. Odds ratios are based on interquartile range (IQR) increases or 10 unit increases when IQR ranges were narrow. Single-pollutant models as well as multipollutant models were examined. Stratification on gender, race, ethnicity and socioeconomic status was explored. RESULTS: The associations with ozone and PM2.5 were strongest on the same day (lag0) of the emergency department visit (RR IQR=1.05, 95% CI 1.04-1.06) and (RR IQR=1.03, 95% CI 1.02-1.04), respectively, with a decreasing lag effect. Tree and weed pollen were associated with pediatric ED visits; the largest magnitudes of association was with the 5-day average (RR IQR=1.23, 95% CI 1.21-1.25) and (RR 10=1.13, 95% CI 1.12-1.14), respectively. Grass pollen was only minimally associated with the outcome while ragweed had a negative association. CONCLUSIONS: The ambient air pollutant ozone is associated with increases in pediatric emergency department asthma visits during the warm weather season. The different pollen types showed different associations with the outcome. High levels of tree pollen appear to be an important risk factor in asthma exacerbations.

The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: patients' experience with allergen immunotherapy.

Allergen immunotherapy (AIT) is used for the treatment of allergic rhinoconjunctivitis as a subcutaneous injection (subcutaneous immunotherapy [SCIT]). Extracts used for SCIT are also used off-label to formulate a liquid delivered as sublingual drops (sublingual immunotherapy [SLIT]). This study was designed to survey patients' experiences and beliefs regarding SCIT and SLIT. People who had ever been diagnosed with nasal and/or ocular allergies were identified in a 2012 telephone survey of U.S. households. Respondents were asked questions about their or their child's use of SCIT and SLIT and their beliefs about AIT. Of 2765 respondents, 46.5% had ever heard of AIT and 22.7% had ever initiated it: 20.9% with SCIT and 1.8% with SLIT (p < 0.0001). The most frequently cited reason for beginning AIT was that symptoms were unresolved with other medications (SCIT, 32.1%; SLIT, 14.0%). Some or full symptom relief was reported by 74.9% of respondents treated with SCIT and 66.0% of those treated with SLIT (p = 0.17 for SCIT versus SLIT). Approximately one-third of respondents who had ever heard of or had been treated with AIT said "don't know" when asked if immunotherapy controls allergy symptoms for years (33.6%), is a very safe treatment (29.3%), or can cure allergy symptoms (27.5%). Effective relief of allergy symptoms was cited most often as the primary benefit of SCIT (37.8%) and convenience was the primary benefit of SLIT (14%). Only one-fifth of respondents had ever been treated with AIT, largely with SCIT. More than one-half of respondents had never heard of AIT and respondents' beliefs indicated a need for educational efforts.

Ocular and nasal allergy symptom burden in America: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.

Previous nationwide surveys of allergies in the United States have focused on nasal symptoms, but ocular symptoms are also relevant. This study determines the effects of ocular and nasal allergies on patients' lives. Telephone surveys of randomly selected U.S. households (the patient survey) and health care providers (provider survey) were conducted in the United States in 2012. Study participants were 2765 people ≥5 years of age who had ever been diagnosed with nasal or ocular allergies and 500 health care providers in seven specialties. Respondents to the patient survey reported a bimodal seasonal distribution of allergy symptoms, with peaks in March to May and September. Nasal congestion was the most common of the symptoms rated as "extremely bothersome" (39% of respondents), followed by red, itchy eyes (34%; p = 0.84 for difference in extreme bothersomeness of nasal and ocular symptoms). Twenty-nine percent of respondents reported that their or their child's daily life was impacted "a lot" when allergy symptoms were at their worst. Workers rated their mean productivity at 29% lower when allergy symptoms were at their worst (p < 0.001 compared with no symptoms). Providers reported that itchy eyes was the symptom causing most patients to seek medical treatment by pediatricians (73%), ophthalmologist/optometrists (72%), and nurse practitioners or physician assistants (62%), whereas nasal congestion was the symptom causing most patients to seek treatment from otolaryngologists (85%), allergist/immunologists (79%), and family medicine practitioners (64%). Ocular and nasal allergy symptoms substantially affected patients' lives and were comparable in their impact.

Recent warming by latitude associated with increased length of ragweed pollen season in central North America.

A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above ~44°N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health.

Climate change effect on Betula (birch) and Quercus (oak) pollen seasons in the United States.

Climatic change is expected to affect the spatiotemporal patterns of airborne allergenic pollen, which has been found to act synergistically with common air pollutants, such as ozone, to cause allergic airway disease (AAD). Observed airborne pollen data from six stations from 1994 to 2011 at Fargo (North Dakota), College Station (Texas), Omaha (Nebraska), Pleasanton (California), Cherry Hill and Newark (New Jersey) in the US were studied to examine climate change effects on trends of annual mean and peak value of daily concentrations, annual production, season start, and season length of Betula (birch) and Quercus (oak) pollen. The growing degree hour (GDH) model was used to establish a relationship between start/end dates and differential temperature sums using observed hourly temperatures from surrounding meteorology stations. Optimum GDH models were then combined with meteorological information from the Weather Research and Forecasting (WRF) model, and land use land coverage data from the Biogenic Emissions Land use Database, version 3.1 (BELD3.1), to simulate start dates and season lengths of birch and oak pollen for both past and future years across the contiguous US (CONUS). For most of the studied stations, comparison of mean pollen indices between the periods of 1994-2000 and 2001-2011 showed that birch and oak trees were observed to flower 1-2 weeks earlier; annual mean and peak value of daily pollen concentrations tended to increase by 13.6%-248%. The observed pollen season lengths varied for birch and for oak across the different monitoring stations. Optimum initial date, base temperature, and threshold GDH for start date was found to be 1 March, 8 °C, and 1,879 h, respectively, for birch; 1 March, 5 °C, and 4,760 h, respectively, for oak. Simulation results indicated that responses of birch and oak pollen seasons to climate change are expected to vary for different regions.

Diagnosis and Treatment of Vernal Keratoconjunctivitis: A Qualitative Study of Caregiver, Patient, and Clinician Experience in the United States.

PURPOSE: To better understand the patient journey and challenges in the diagnosis and treatment of patients with vernal keratoconjunctivitis (VKC). METHODS: This qualitative study assessed the experience of caregivers of children with VKC (n = 7) and of clinicians who treat VKC (n = 16) in the United States. The structured interviews were conducted to identify key "pain points", obstacles, and trends on the path to diagnosis. RESULTS: Like an earlier study conducted in the United Kingdom, this study found low awareness of the nature and severity of VKC among U.S. caregivers and non-specialist providers, and a tendency among young patients and their caregivers to downplay initial symptoms. Medical intervention was delayed as caregivers treated symptoms with over-the-counter medications; 88% (14 of 16) of specialists reported frequent misdiagnosis and mistreatment by pediatricians and primary care providers who were initial points of care. Time to appropriate referral ranged from 1 to 2 weeks to 3 months, in part due to convoluted referral pathways that were universal points of frustration for caregivers and specialists. CONCLUSIONS: Limited awareness of VKC remains a barrier to timely identification and management of this rare but disruptive ocular surface disease. Caregivers underestimate symptom severity, pediatricians and primary care providers often misdiagnose VKC as allergy or infection, and referrals to appropriate specialists are delayed until symptoms are severe. Early identification is essential to improving the diagnostic journey and treatment of VKC. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].