@article {1456, title = {Association of weather variables with pathogens contributing to conjunctivitis worldwide.}, journal = {Clin Infect Dis}, year = {2024}, month = {2024 Aug 19}, abstract = {

PURPOSE: To identify weather variables associated with pathogens contributing to infectious conjunctivitis globally.

METHODS: Sample collection and pathogen identification from patients with acute infectious conjunctivitis was performed from 2017 to 2023. We linked pathogens identified from 13 sites across 8 countries with publicly available weather data by geographic coordinates. Mixed effects logistic regression analysis was performed to estimate the associations between temperature, precipitation, and relative humidity exposures, and the prevalence of infection types (RNA virus, DNA virus, bacteria, and fungus).

RESULTS: 498 cases from the United States, India, Nepal, Thailand, Burkina Faso, Niger, Vietnam, and Israel were included in the analysis. 8-day average precipitation (mm) was associated with increased odds of RNA virus infection (odds ratio (OR)=1.47, 95\% confidence interval (CI): 1.12 to 1.93, P=0.01) and decreased odds of DNA infection (OR=0.62, 95\% CI: 0.46 to 0.82, P\<0.001). Relative humidity (\%) was associated with increased odds of RNA virus infections (OR=2.64, 95\% CI: 1.51 to 4.61, P\<0.001), and fungal infections (OR=2.35, 95\% CI: 1.19 to 4.66, P=0.01), but decreased odds of DNA virus (OR=0.58, 95\%CI: 0.37 to 0.90, P=0.02) and bacterial infections (OR=0.42, 95\% CI: 0.25 to 0.71, P\<0.001). Temperature ({\textdegree}C) was not associated with ocular infections for any pathogen type.

CONCLUSIONS: This study suggests that weather factors affect pathogens differently. Particularly, humidity and precipitation were predictors for pathogens contributing to conjunctivitis worldwide. Additional work is needed to clarify the effects of shifts in weather and environmental factors on ocular infectious diseases.

}, issn = {1537-6591}, doi = {10.1093/cid/ciae417}, author = {Yan, Daisy and Prajna, N Venkatesh and Lalitha, Prajna and Sansanayudh, Wiwan and Satitpitakul, Vannarut and Laovirojjanakul, Wipada and Chaudhary, Meenu and Bountogo, Mamadou and Sie, Ali and Coulibaly, Boubacar and Amza, Abdou and Nassirou, Beido and Almou, Ibrahim and Tran, Huy and Tran, Yen and Tsui, Edmund and Onclinx, Tania and Sella, Ruti and Goren, Lee and McClean, Esmeralda and Tham, Vivien and Chen, Cindi and Ruder, Kevin and Zhong, Lina and Liu, YuHeng and Yu, Danny and Abraham, Thomas and Lebas, Elodie and Arnold, Benjamin F and McLeod, Stephen D and Deiner, Michael S and Porco, Travis C and Seitzman, Gerami D and Lietman, Thomas M and Shantha, Jessica and Hinterwirth, Armin and Doan, Thuy} } @article {1451, title = {Biomarker Detection and Validation for Corneal Involvement in Patients With Acute Infectious Conjunctivitis.}, journal = {JAMA Ophthalmol}, year = {2024}, month = {2024 Aug 15}, abstract = {

IMPORTANCE: Infectious conjunctivitis can lead to corneal involvement and result in ocular morbidity. The identification of biomarkers associated with corneal involvement has the potential to improve patient care.

OBJECTIVE: To identify biomarkers in patients with acute infectious conjunctivitis.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study took place from December 2016 to March 2024. Analyses were performed in 3 phases. First, logistic regression and machine learning algorithms were used to predict the probability of demonstrating corneal involvement in patients with presumed infectious conjunctivitis. Second, quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to confirm the most important biomarker gene identified by the algorithm. Third, the biomarker gene was validated in prospectively collected conjunctival samples of adult patients from 3 outpatient centers in Thailand and 1 in India. Patients with signs and symptoms of infectious conjunctivitis and onset within less than 14 days were eligible. Exclusion criteria were the inability to consent, presumed toxicity, or allergic conjunctivitis.

EXPOSURES: Acute infectious conjunctivitis.

MAIN OUTCOMES AND MEASURES: The identification and validation of ocular surface gene expression associated with corneal findings on slitlamp examination.

RESULTS: Thirteen genes exhibited a 1.5-log2 fold change in expression in patients with corneal involvement compared to patients without corneal involvement. Using the 13 genes to train and cross validate, logistic regression produced the highest mean area under the receiver operating characteristic curve (AUROC; 0.85; 95\% CI, 0.84-0.86) for corneal involvement. The removal of apolipoprotein E (APOE) from the gene ensemble led to a decline in predictive performance of the logistic regression classifier (from mean AUROC 0.85 [95\% CI, 0.84-0.86] to 0.74 [95\% CI, 0.73-0.75]; adjusted P = .001 [Tukey test]). Orthogonal testing of APOE expression level with RT-qPCR showed that APOE expression was higher in patients with corneal involvement compared to patients without (median [IQR], 0.23 [0.04-0.47] vs 0.04 [0.02-0.06]; P = .004 [Mann-Whitney U test]). Using a Youden index of 0.23 Δ threshold cycle, APOE had a sensitivity of 56\% (95\% CI, 33-77) and a specificity of 88\% (95\% CI, 79-93) in 106 samples with conjunctivitis at Aravind, India (P < .001 [Fisher exact test]). When applied to a different patient population in Thailand, the same criteria could discriminate between disease states (58 samples; sensitivity, 47\%; 95\% CI, 30-64 and specificity, 93\%; 95\% CI, 77-99; P = .001 [Fisher exact test]).

CONCLUSIONS AND RELEVANCE: The results from this study suggest that the host conjunctival immune response can be meaningfully interrogated to identify biomarkers for ocular surface diseases.

}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2024.2891}, author = {Seitzman, Gerami D and Prajna, Lalitha and Prajna, N Venkatesh and Sansanayudh, Wiwan and Satitpitakul, Vannarut and Laovirojjanakul, Wipada and Chen, Cindi and Zhong, Lina and Ouimette, Kevin and Redd, Travis and Deiner, Michael C and Porco, Travis C and McLeod, Stephen D and Lietman, Thomas M and Hinterwirth, Armin and Doan, Thuy} } @article {1371, title = {Use of Large Language Models to Assess the Likelihood of Epidemics From the Content of Tweets: Infodemiology Study.}, journal = {J Med Internet Res}, volume = {26}, year = {2024}, month = {2024 Mar 01}, pages = {e49139}, abstract = {

BACKGROUND: Previous work suggests that Google searches could be useful in identifying conjunctivitis epidemics. Content-based assessment of social media content may provide additional value in serving as early indicators of conjunctivitis and other systemic infectious diseases.

OBJECTIVE: We investigated whether large language models, specifically GPT-3.5 and GPT-4 (OpenAI), can provide probabilistic assessments of whether social media posts about conjunctivitis could indicate a regional outbreak.

METHODS: A total of 12,194 conjunctivitis-related tweets were obtained using a targeted Boolean search in multiple languages from India, Guam (United States), Martinique (France), the Philippines, American Samoa (United States), Fiji, Costa Rica, Haiti, and the Bahamas, covering the time frame from January 1, 2012, to March 13, 2023. By providing these tweets via prompts to GPT-3.5 and GPT-4, we obtained probabilistic assessments that were validated by 2 human raters. We then calculated Pearson correlations of these time series with tweet volume and the occurrence of known outbreaks in these 9 locations, with time series bootstrap used to compute CIs.

RESULTS: Probabilistic assessments derived from GPT-3.5 showed correlations of 0.60 (95\% CI 0.47-0.70) and 0.53 (95\% CI 0.40-0.65) with the 2 human raters, with higher results for GPT-4. The weekly averages of GPT-3.5 probabilities showed substantial correlations with weekly tweet volume for 44\% (4/9) of the countries, with correlations ranging from 0.10 (95\% CI 0.0-0.29) to 0.53 (95\% CI 0.39-0.89), with larger correlations for GPT-4. More modest correlations were found for correlation with known epidemics, with substantial correlation only in American Samoa (0.40, 95\% CI 0.16-0.81).

CONCLUSIONS: These findings suggest that GPT prompting can efficiently assess the content of social media posts and indicate possible disease outbreaks to a degree of accuracy comparable to that of humans. Furthermore, we found that automated content analysis of tweets is related to tweet volume for conjunctivitis-related posts in some locations and to the occurrence of actual epidemics. Future work may improve the sensitivity and specificity of these methods for disease outbreak detection.

}, issn = {1438-8871}, doi = {10.2196/49139}, author = {Deiner, Michael S and Deiner, Natalie A and Hristidis, Vagelis and McLeod, Stephen D and Doan, Thuy and Lietman, Thomas M and Porco, Travis C} } @article {916, title = {Very late onset LASIK flap Acremonium fungal keratitis confirmed by metagenomic deep sequencing.}, journal = {Am J Ophthalmol Case Rep}, volume = {25}, year = {2022}, month = {2022 Mar}, pages = {101294}, abstract = {

Purpose: To describe a unique case of LASIK flap fungal keratitis confirmed by next generation sequencing.

Observations: A 56-year-old female presented with refractory keratitis involving her LASIK flap 21 years after surgery. Confocal was positive for filamentous structures. The patient underwent immediate flap amputation followed by topical antifungal treatment. Corneal culture was positive for sp. Metagenomic deep sequencing confirmed as the primary source of infection and also identified as a likely contributor of a mixed fungal infection. Sequencing also identified hay as the likely source of the infection. Treatment resulted in eradication of the infection. The patient{\textquoteright}s final best corrected visual acuity was 20/30 with rigid contact lens overrefraction.

Conclusions: Metagenomic deep sequencing is a novel diagnostic tool that is increasingly being utilized for diagnosis of refractory keratitis. This case demonstrates the diagnostic potential of deep sequencing for identifying post-LASIK keratitis and reinforces the utility of LASIK flap amputation in the setting of tectonic flap instability due to keratolysis.

Importance: This case highlights several important clinical points for treating LASIK flap keratitis and highlights the emerging role metagenomic sequencing has in the diagnosis of infectious keratitis. This is first known case using next generation sequencing to diagnose a post-LASIK infectious keratitis.

}, issn = {2451-9936}, doi = {10.1016/j.ajoc.2022.101294}, author = {Greenwald, Miles F and Redd, Travis K and Doan, Thuy and McLeod, Stephen D and Seitzman, Gerami D} } @article {906, title = {Keeping an eye on pink eye: a global conjunctivitis outbreak expert survey.}, journal = {Int Health}, year = {2021}, month = {2021 Aug 19}, abstract = {

BACKGROUND: Recurrent conjunctivitis epidemics are prevalent worldwide. Aetiologies are often undetermined.

METHODS: We surveyed conjunctivitis researchers about perceived trends in prevalence, incidence and aetiologies of conjunctivitis epidemics.

RESULTS: Of the 155 participants, 7\% endorsed globally variable and dynamic microbial aetiologies of conjunctivitis epidemics. Increased incidence of conjunctivitis epidemics over the last decade were reported by 21\% of respondents. Peak seasons differed between the northern and southern hemispheres.

CONCLUSIONS: There is regional equipoise regarding the increasing incidence and emerging underlying aetiologies of epidemic conjunctivitis. Further investigation of global surveillance and microbial characterization of conjunctivitis outbreaks could improve prevention and outcomes.

}, issn = {1876-3405}, doi = {10.1093/inthealth/ihab049}, author = {Kaur, Gurbani and Seitzman, Gerami D and Lietman, Thomas M and McLeod, Stephen D and Porco, Travis C and Doan, Thuy and Deiner, Michael S} } @article {61, title = {Infectious corneal ulceration: a proposal for neglected tropical disease status.}, journal = {Bull World Health Organ}, volume = {97}, year = {2019}, month = {2019 Dec 01}, pages = {854-856}, keywords = {Anti-Bacterial Agents, Bacterial Infections, Corneal Ulcer, Developing Countries, Global Health, Health Promotion, Humans, Leprosy, Neglected Diseases, Onchocerciasis, Ocular, Trachoma}, issn = {1564-0604}, doi = {10.2471/BLT.19.232660}, author = {Ung, Lawson and Acharya, Nisha R and Agarwal, Tushar and Alfonso, Eduardo C and Bagga, Bhupesh and Bispo, Paulo Jm and Burton, Matthew J and Dart, John Kg and Doan, Thuy and Fleiszig, Suzanne Mj and Garg, Prashant and Gilmore, Michael S and Gritz, David C and Hazlett, Linda D and Iovieno, Alfonso and Jhanji, Vishal and Kempen, John H and Lee, Cecilia S and Lietman, Thomas M and Margolis, Todd P and McLeod, Stephen D and Mehta, Jod S and Miller, Darlene and Pearlman, Eric and Prajna, Lalitha and Prajna, N Venkatesh and Seitzman, Gerami D and Shanbhag, Swapna S and Sharma, Namrata and Sharma, Savitri and Srinivasan, Muthiah and Stapleton, Fiona and Tan, Donald Th and Tandon, Radhika and Taylor, Hugh R and Tu, Elmer Y and Tuli, Sonal S and Vajpayee, Rasik B and Van Gelder, Russell N and Watson, Stephanie L and Zegans, Michael E and Chodosh, James} }