Correlation of Adenoviral Titers with Severity of Adenoviral Conjunctivitis and Time to Viral Clearance for 21 Days.

SIGNIFICANCE: This investigation reports the correlation of conjunctival viral titers in adenoviral conjunctivitis with patient-reported symptoms and clinician-graded signs for 21 days of follow-up. PURPOSE: Adenoviral conjunctivitis is a highly contagious viral eye infection with significant morbidity and economic impact. This study investigates whether severity of signs and symptoms and time to viral clearance are correlated with conjunctival viral titers at baseline and during 21 days of follow-up. METHODS: The Reducing Adenoviral Patient Infected Days study was a pilot study of the efficacy of a single in-office administration of ophthalmic 5% povidone-iodine. This article outlines longitudinal analyses after the primary outcome report. Of 212 participants screened, 28 participants with quantitative polymerase chain reaction-confirmed adenoviral conjunctivitis were randomized and had follow-up visits on days 1, 2, 4, 7, 14, and 21. At each visit, clinician-graded signs, participant-reported symptoms, and a conjunctival swab for quantitative polymerase chain reaction analysis were obtained. The correlation of viral titers with symptoms and signs was calculated: (1) cross-sectionally at each visit and (2) longitudinally for 21 days using a repeated-measures mixed-effects model. RESULTS: Twenty-five of 28 participants had sufficient data for this report. Higher viral titers for 21 days were correlated with greater severity of symptoms (tearing, matting, and redness, r ≥ 0.70; P < .02) and greater severity of clinical signs (bulbar redness and serous discharge, r ≥ 0.60; P < .01). Eyes with highest baseline viral titers required longer time to viral clearance ( r = 0.59, P = .008). Signs and symptoms persisted in approximately half of the eyes even after viral clearance. CONCLUSIONS: Higher conjunctival viral titers across 21 days were strongly correlated with more severe signs and symptoms and longer time to viral clearance. Our results also indicate that symptoms and signs can persist after viral clearance.

Case Series: Unbiased Deep Sequencing Analysis of Acute Infectious Conjunctivitis in an Ambulatory Eye Center in Berkeley, California.

SIGNIFICANCE: Acute infectious conjunctivitis poses significant challenges to eye care providers. It can be highly transmissible, and because etiology is often presumed, correct treatment and management can be difficult. This study uses unbiased deep sequencing to identify causative pathogens of infectious conjunctivitis, potentially allowing for improved approaches to diagnosis and management. PURPOSES: This study aimed to identify associated pathogens of acute infectious conjunctivitis in a single ambulatory eye care center. CASE REPORTS: This study included patients who presented to the University of California Berkeley eye center with signs and symptoms suggestive of infectious conjunctivitis. From December 2021 to July 2021, samples were collected from seven subjects (ages ranging from 18 to 38). Deep sequencing identified associated pathogens in five of seven samples, including human adenovirus D, Haemophilus influenzae , Chlamydia trachomatis , and human coronavirus 229E. CONCLUSIONS: Unbiased deep sequencing identified some unexpected pathogens in subjects with acute infectious conjunctivitis. Human adenovirus D was recovered from only one patient in this series. Although all samples were obtained during the COVID-19 pandemic, only one case of human coronavirus 229E and no SARS-CoV-2 were identified.

Success of Masking 5% Povidone-Iodine Treatment: The Reducing Adenoviral Patient Infected Days Study.

SIGNIFICANCE: The effectiveness of masking is rarely evaluated or reported in single- or double-masked clinical trials. Knowledge of treatment assignment by participants and clinicians can bias the assessment of treatment efficacy. PURPOSE: This study aimed to evaluate the effectiveness of masking in a double-masked trial of 5% povidone-iodine for the treatment of adenoviral conjunctivitis. METHODS: The Reducing Adenoviral Patient Infected Days study is a double-masked, randomized trial comparing a one-time, in-office administration of 5% povidone-iodine with artificial tears for the treatment of adenoviral conjunctivitis. Masking was assessed by asking participants and masked clinicians at designated time points if they believed the treatment administered was povidone-iodine or artificial tears, or if they were unsure. Adequacy of masking was quantified using a modified Bang Blinding Index. RESULTS: Immediately after treatment, 34% of participants who received povidone-iodine and 69% of those who received artificial tears guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.31 and -0.38, respectively). On day 4, 38% of the povidone-iodine participants and 52% of the artificial tear participants guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.24 and -0.05, respectively), indicating adequate and ideal masking. On days 1, 4, 7, 14, and 21, masked clinicians guessed incorrectly or were unsure of treatment in 53%, 50%, 40%, 39%, and 42% among povidone-iodine participants compared with 44%, 35%, 38%, 35%, and 39% among artificial tears participants, respectively. The modified Bang Indices for clinician masking in the povidone-iodine group ranged from -0.05 to 0.25 and from 0.13 to 0.29 in the artificial tears group. CONCLUSIONS: Masking of participants and clinicians was adequate. Successful masking increases confidence that subjective measurements are not biased. We recommend quantitative assessment and reporting the effectiveness of masking in ophthalmic clinical trials.

Natural history of adenoviral conjunctivitis in a US-based population: Viral load, signs, and symptoms.

PURPOSE: To report the clinical signs, symptoms, and viral clearance in individuals in the United States with adenoviral conjunctivitis (Ad-Cs). METHODS: Individuals ≥ 18 years presenting within 4 days of symptoms of Ad-Cs who met eligibility criteria and tested positive with both point-of-care immunoassay antigen and quantitative polymerase chain reaction (qPCR) testing were enrolled. Patient-reported symptoms, clinician-graded signs, and qPCR viral titers were collected at baseline, days 1-2, 4 (days 3-5), 7 (days 6-10), 14 (days 11-17) and 21 (days 18-21). RESULTS: There was no detectable viral titers by the day 14 visit in 6/8 patients. By day 21, there was no detectable viral titers in the 7 participants who completed the visit; however, signs and symptoms persisted including: blurry vision (5/7), discomfort (2/7) or redness (1/7). Masked clinicians also noted conjunctival redness (4/7), follicular conjunctivitis (4/7) and bulbar edema (3/7). CONCLUSION: Many patient-reported symptoms and clinical signs persist after viral titers are no longer detectable by qPCR. Using clinical signs and symptoms to determine quarantine duration may result in patients being furloughed longer than the time that the patient is infectious.

Diagnostic accuracy of clinical signs, symptoms and point-of-care testing for early adenoviral conjunctivitis.

CLINICAL RELEVANCE: This study identifies key signs and symptoms of acute conjunctivitis, that when combined with a point-of-care test, can improve clinician accuracy of diagnosing adenoviral conjunctivitis. BACKGROUND: Adenoviral conjunctivitis is a common ocular infection with the potential for high economic impact due to widespread outbreaks and subsequent furloughs from work and school. In this report, we describe clinical signs and participant-reported symptoms that most accurately identify polymerase chain reaction (PCR)-confirmed adenoviral conjunctivitis. METHODS: Adults with 'red eye' symptoms of four days or less were enrolled. Participants rated 10 ocular symptoms from 0 (not bothersome) to 10 (very bothersome), and indicated the presence or absence of systemic flu-like symptoms. Clinicians determined the presence or absence of swollen lymph nodes and rated the severity of eight ocular signs using a 5-point scale. An immunoassay targeting adenovirus antigen was utilised for the point-of-care test, and conjunctival swab samples were obtained for subsequent adenovirus detection by PCR analyses. Univariate and multivariate logistic regression models were used to identify symptoms and signs associated with PCR-confirmed adenoviral conjunctivitis. The diagnostic accuracy of these clinical findings, and the potential benefit of incorporating point-of-care test results, was assessed by calculating areas under the receiver operating characteristic curves (AUC). RESULTS: Clinician-rated bulbar conjunctival redness, participant-rated eyelid swelling and overall ocular discomfort had the best predictive value in the multivariate logistic regression model with an AUC of 0.83. The addition of the point-of-care test results to these three clinical sign/symptom scores improved diagnostic accuracy, increasing the AUC to 0.94. CONCLUSIONS: Conjunctival redness severity and participant-reported eyelid swelling and overall discomfort, along with adenoviral point-of-care test results, were highly predictive in identifying individuals with PCR-confirmed adenoviral conjunctivitis. Improved diagnostic accuracy by clinicians at the initial presenting visit could prevent unnecessary work furloughs and facilitate earlier treatment decisions.

Efficacy of a Single Administration of 5% Povidone-Iodine in the Treatment of Adenoviral Conjunctivitis.

PURPOSE: To evaluate the safety and efficacy of a single, in-office administration of 5% povidone-iodine (PVP-I) compared to artificial tears (AT) for adenoviral conjunctivitis (Ad-Cs). DESIGN: Double-masked pilot randomized trial. METHODS: Patients presenting with presumed adenoviral conjunctivitis were screened at 9 U.S. clinics. INCLUSION CRITERIA: ≥18 years of age, symptoms ≤4 days, and a positive AdenoPlus test. EXCLUSION CRITERIA: thyroid disease, iodine allergy, recent ocular surgery, and ocular findings inconsistent with early-stage Ad-Cs. Randomization was to a single administration of 5% PVP-I or AT in 1 eye and examinations on days 1-2, 4, 7, 14, and 21 with conjunctival swabs taken at each visit for quantitative polymerase chain reaction. Primary outcome was percent reduction from peak viral load. Secondary outcomes were improvement in clinical signs and symptoms. RESULTS: Of 56 patients randomized, 28 had detectable viral titers at baseline. Day 4 posttreatment, viral titers in the 5% PVP-I and AT groups were 2.5% ± 2.7% and 14.4% ± 10.5% of peak, respectively (P = .020). Severity of participant-reported tearing, lid swelling, and redness as well as clinician-graded mucoid discharge, bulbar redness, and bulbar edema were lower in the 5% PVP-I group than AT group on day 4 (P < .05). After day 4, viral titers and severity of signs and symptoms decreased markedly in both groups and no differences between groups were detected. CONCLUSIONS: Pilot data suggest a single, in-office administration of 5% PVP-I could reduce viral load and hasten improvement of clinical signs and symptoms in patients with Ad-Cs.

Predictive Accuracy and Densitometric Analysis of Point-of-Care Immunoassay for Adenoviral Conjunctivitis.

Purpose: Accurate diagnosis of adenoviral conjunctivitis (Ad-Cs) is important for timely and appropriate patient management to reduce disease transmission. This study assessed the diagnostic accuracy of a commercially available point-of-care adenovirus immunoassay and determined whether its predictive accuracy is influenced by signal intensities of test result bands. Methods: Point-of-care immunoassay (AdenoPlus) testing and quantitative polymerase chain reaction (qPCR) testing was performed on conjunctival swab samples obtained from eyes of 186 eligible adult participants with presumed infectious conjunctivitis and symptoms of ≤4 days. Masked observers assessed signal intensities of the immunoassay test and control bands using densitometry. Results: Ad-Cs was confirmed by qPCR in 28 of the 56 eyes that tested positive on the AdenoPlus, a 50% positive predictive value (95% confidence interval [CI] = 36.9, 63.1). No adenovirus was detected by qPCR in 128 of 130 eyes that tested negative on AdenoPlus, a 98.5% negative predictive value (CI = 96.3, 100). Sensitivity and specificity were 93% (CI = 84.4, 100) and 82% (CI = 76.0, 88.1), respectively. Viral titers significantly correlated with ratio of test band signal intensities (R2 = 0.32, P = 0.002). Higher positive predictive value was associated with higher densitometry ratios (receiver operating characteristic [ROC] area = 0.71; 95% CI = 0.59, 0.83). Conclusions: Densitometric analyses suggest that the diagnostic accuracy of AdenoPlus is influenced by the signal intensity of the test result bands. Visual comparison of the test band intensities by clinicians could reduce the false positive rate of point-of-care immunoassays and aid in the diagnosis of viral infections. Translational Relevance: Ratiometric densitometry of point-of-care immunoassays could aid clinicians' decision making in diagnosing infectious diseases, including Ad-Cs.

Safety and tolerability of a one-time, in-office administration of 5% povidone-iodine in the treatment of adenoviral conjunctivitis: The Reducing Adenoviral Patient Infected Days (RAPID) study.

PURPOSE: To report safety and tolerability of a one-time administration of ophthalmic 5% povidone-iodine (5% PVP-I) in a double-masked randomized trial for the treatment of adenoviral conjunctivitis (Ad-Cs). METHODS: Of 212 participants screened, 56 eligible participants with red eye symptoms ≤4 days and a positive adenoviral rapid immunoassay were randomized to a one-time administration of ophthalmic 5% PVP-I or preservative free artificial tears (AT). Safety was assessed by corneal fluorescein staining (baseline, immediate post-administration and Day 1) and visual acuity (VA) (baseline and Day 1). Tolerability was assessed using participant-rated overall ocular discomfort (baseline, immediately post-administration and on Day 1. RESULTS: In the 5% PVP-I group, corneal staining increased immediately post-administration but returned to baseline levels by Day 1. There was no change in VA between baseline and Day 1 in either 5% PVP-I or AT groups (p = 0.87). In the 5% PVP-I group, there was no change in participant-rated overall discomfort immediately post-administration (p = 0.78) or on day 1 (p = 0.10) compared to baseline. In the AT group, participant-rated overall discomfort was lower immediately post-administration but returned to baseline levels by Day 1. One adverse event was reported in the 5% PVP-I group on Day 1-2 that was classified as not related to treatment. CONCLUSION: These results suggest ophthalmic 5% PVP-I used as a one-time treatment is safe and well tolerated by patients with Ad-Cs.

Sensory impairment in older adults: Part 1: Hearing loss.

Preserving older adults' sense of hearing and helping them to maintain communication in the face of changes that occur with age are areas of concern for nurses. In addition to reviewing the types of hearing impairment, this article emphasizes assessment strategies and interventions that nurses can use across settings. This is Part 1 of a two-part article on sensory impairment in older adults; in the November 2006 issue, Part 2 will address visual impairment in this population.

Sensory impairment in older adults: part 2: Vision loss.

A decline in vision occurs naturally with age; more severe impairment can result from medical conditions such as age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy. Nurses can pick up signs of visual impairment and suggest certain environmental modifications to prevent injury, such as keeping floors free of clutter and rooms well lit. Although assistive technologies such as optical devices, magnifiers, telescopes, and electronic magnification can help, some forms of impairment, such as that caused by cataracts and uncorrected refractive error, can be corrected.