Machine Learning Prediction of Adenovirus D8 Conjunctivitis Complications from Viral Whole-Genome Sequence.

Objective: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes. Design: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis. Participants: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study. Methods: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods. Main Outcome Measures: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures. Results: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83% for Clade 1 to 46% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases (P = 1.5 × 10-5). Prediction was dependent on ensemble groups of polymorphisms across multiple genes. Conclusions: Adenovirus D8 has ≥ 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity.

Punctal Stenosis Associated with Topical Netarsudil Use.

PURPOSE: To report a series of patients who developed punctal stenosis secondary to the use of topical netarsudil 0.02% for treatment of glaucoma. DESIGN: Case series. PARTICIPANTS: Patients using topical netarsudil for management of glaucoma and noted to have punctal stenosis ipsilateral to the eye(s) being treated with netarsudil were included. METHODS: Each enrolled patient's chart was reviewed, and alternative causes of punctal stenosis were sought. Photographs were obtained to document punctal stenosis for some patients. MAIN OUTCOME MEASURES: Presence of punctal stenosis after topical netarsudil use and resolution of punctal stenosis after cessation of therapy. RESULTS: Sixteen patients had punctal stenosis; 13 developed unilateral punctal stenosis while using netarsudil unilaterally, and 3 patients developed bilateral punctal stenosis with bilateral use. Time from initiation of netarsudil to recognition of symptoms or documentation of punctal stenosis ranged from 2 to 35 months (median, 12; mean, 14.0 ± 8.7 months). Thirteen patients endorsed tearing, but 2 had no symptoms. Ectropion was seen in 1 eye. Corneal verticillata was noted in 14 patients (87.5%). In 8 cases, netarsudil was discontinued, and the punctal stenosis was reversed, with resolution of associated symptoms. CONCLUSIONS: Netarsudil use can lead to the development of reversible punctal stenosis. This inflammation-mediated stenosis may cause tearing and associated symptoms and may be of sufficient severity to necessitate discontinuation of treatment. In this case series, all patients who discontinued treatment had reversal of their punctal stenosis and associated symptoms.

Association of Public Health Measures During the COVID-19 Pandemic With the Incidence of Infectious Conjunctivitis.

Importance: Infectious conjunctivitis is highly transmissible and a public health concern. While mitigation strategies have been successful on a local level, population-wide decreases in spread are rare. Objective: To evaluate whether internet search interest and emergency department visits for infectious conjunctivitis were associated with public health interventions adopted during the COVID-19 pandemic. Design, Setting, and Participants: Internet search data from the US and emergency department data from a single academic center in the US were used in this study. Publicly available smartphone mobility data were temporally aligned to quantify social distancing. Internet search term trends for nonallergic conjunctivitis, corneal abrasions, and posterior vitreous detachments were obtained. Additionally, all patients who presented to a single emergency department from February 2015 to February 2021 were included in a review. Physician notes for emergency department visits at a single academic center with the same diagnoses were extracted. Causal inference was performed using a bayesian structural time-series model. Data were compared from before and after April 2020, when the US Centers for Disease Control and Prevention recommended members of the public wear masks, stay at least 6 feet from others who did not reside in the same home, avoid crowds, and quarantine if experiencing flulike symptoms or exposure to persons with COVID-19 symptoms. Exposures: Symptoms of or interest in conjunctivitis in the context of the COVID-19 pandemic. Main Outcome and Measures: The hypothesis was that there would be a decrease in internet search interest and emergency department visits for infectious conjunctivitis after the adaptation of public health measures targeted to curb COVID-19. Results: A total of 1156 emergency department encounters with a diagnosis of conjunctivitis were noted from January 2015 to February 2021. Emergency department encounters for nonallergic conjunctivitis decreased by 37.3% (95% CI, -12.9% to -60.6%; P < .001). In contrast, encounters for corneal abrasion (1.1% [95% CI, -29.3% to 29.1%]; P = .47) and posterior vitreous detachments (7.9% [95% CI, -46.9% to 66.6%]; P = .39) remained stable after adjusting for total emergency department encounters. Search interest in conjunctivitis decreased by 34.2% (95% CI, -30.6% to -37.6%; P < .001) after widespread implementation of public health interventions to mitigate COVID-19. Conclusions and Relevance: Public health interventions, such as social distancing, increased emphasis on hygiene, and travel restrictions during the COVID-19 pandemic, were associated with decreased search interest in nonallergic conjunctivitis and conjunctivitis-associated emergency department encounters. Mobility data may provide novel metrics of social distancing. These data provide evidence of a sustained population-wide decrease in infectious conjunctivitis.

Regression of Intraocular Rosai- Dorfman Disease Following Treatment with Photodynamic Therapy.

Rosai-Dorfman disease (RDD), a rare form of histiocytosis, has been reported to cause choroidal masses and subsequent serous retinal detachments. We present a case of RDD associated with a choroidal mass and retinal detachment that did not respond to corticosteroid treatment and regressed after treatment with photodynamic therapy (PDT). Following treatment, the patient had a successful anatomic and clinical outcome, with no recurrence of serous detachment and 20/25 visual acuity. This is the first report of choroidal RDD successfully treated with PDT. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:568-571.].

Leptotrichia species isolated from a chronic recurrent corneal ulcer.

PURPOSE: To report a case of recurrent corneal ulcer caused by an oropharyngeal cavity pathogen. OBSERVATIONS: A patient presented with recurrent corneal ulcers with hypopyon. Leptotrichia species was eventually isolated from the corneal ulcer on bacterial polymerase chain reaction (PCR) after many negative bacterial culture attempts. Due to correct identification of the pathogen, it was discovered that the patient was exposing her eye to saliva. Modification of patient behavior and initiation of the appropriate antibacterial treatment resulted in resolution of recurrent episodes of active infection. CONCLUSIONS: Although Leptotrichia species are not typically ocular pathogens, they can become pathogenic in the cornea with direct transmission from the oral cavity to the eye.

Determining the Prevalence and Costs of Unnecessary Referrals in Adolescent Idiopathic Scoliosis.

Background: Adolescent idiopathic scoliosis (AIS) has been associated with unnecessary referrals, but the provider and patient costs associated with these referrals remain unknown. The purpose of this study was to determine the prevalence and associated costs of unnecessary referrals for AIS in a university hospital-based orthopaedic clinic. These data are required to estimate the cost-efficacy of scoliosis screening programs. Methods: We accessed the electronic medical records of all patients referred during 2013-2014 with suspected AIS. Spine radiographs were reviewed to determine whether the referral was "unnecessary," defined as a Cobb angle <20 degrees. Patient and provider costs were estimated. Patient costs included transportation expenses and parental lost wages. Provider costs included orthopaedic evaluation, diagnostic imaging, and overhead. Transportation costs were based on actual driving distances and the Internal Revenue Service standard mileage rate. Parental lost wages and the cost of evaluation by an orthopaedic surgeon were calculated with time-driven activity-based costing. Diagnostic imaging costs were calculated with a traditional activity-based costing methodology. Results: Three hundred thirty-seven patients were included. The prevalence of unnecessary referrals was 39% (n=131). 17% of patients had a Cobb angle <10 degrees and 22% had a Cobb angle between 10-20 degrees. Males were more likely to be referred unnecessarily than females, 49% to 35% (p=0.02) as were non-Caucasians (54% vs. 37%, p=0.04). No difference was noted related to source of insurance (private or public, p=0.18). The average total cost of an unnecessary referral was $782.13 USD, including $231.07 in patient costs and $551.06 in provider costs. Conclusions: Nearly 40% of all referrals for AIS were deemed unnecessary. The average cost of an unnecessary referral is approximately $780, imposing significant costs on both patients and the healthcare system.Level of Evidence: III.