Allergic rhinitis and keratoconus: a systematic review and meta-analysis.

BACKGROUND: The relationship between keratoconus and various allergic diseases has been a subject of controversy. OBJECTIVE: In the present study, a systematic review and meta-analysis was conducted to investigate the association between allergic rhinitis (AR) and keratoconus. METHODS: Relevant and eligible studies from PubMed, Web of Science, and Cochrane Library were systematically reviewed to evaluate the association between AR and keratoconus. Observational studies containing the number of patients with and without keratoconus and the number of patients with keratoconus diagnosed with or without AR were included. Two reviewers independently screened for eligible studies and extracted data from the included studies. A bivariate meta-analysis was conducted to compare the odds of keratoconus occurrence in patients with and without AR. The main outcome was the odds ratio of keratoconus occurrence in patients with AR. A sensitivity test was performed using the adjusted odds ratio reported in the included studies to validate the findings. RESULTS: Seven studies involving 775,574 participants were included in this meta-analysis. Among them, 29,082 patients had keratoconus. The pooled odds ratio of keratoconus occurrence in patients with AR was 1.71 (95% confidence interval [CI]: 1.36-2.15; P < 0.001; I2 = 96%), and the pooled adjusted odds ratio was 1.72 (95% CI: 1.23-2.40; P = 0.001; I2 = 97%). CONCLUSION: Patients with AR showed significantly higher odds of keratoconus occurrence than those without AR. Future studies are warranted to investigate the causal relationship and evaluate the cost-effectiveness of early screening using methods such as corneal topography and referral for keratoconus in patients with AR.

Patient-Reported Outcomes and Higher Order Aberrations Following Topography-Guided Femtosecond Laser-Assisted In Situ Keratomileusis.

PURPOSE: To examine patient-reported outcomes and higher order aberrations following topography-guided laser-assisted in situ keratomileusis (LASIK). METHODS: This was a prospective, nonrandomized observational study at a single academic center. Sixty eyes from 30 patients underwent bilateral topography-guided femtosecond LASIK for correction of myopia using the VisuMax 500 femtosecond laser (Zeiss; Oberkochen, Germany) and Allegretto Wave Eye-Q 400 Hz Excimer Laser (Alcon/Wavelight; Erlangen, Germany) with the Contoura topography system (Alcon; Geneva, Switzerland) for topography-modified refraction. The main outcomes of this study were higher order aberrations (HOAs) and results from the Patient-Reported Outcomes with LASIK questionnaire. RESULTS: There was a small, significant increase in HOA root mean square, spherical aberration, and coma at 1, 3, 6, and 12 months following topography-guided LASIK (all P < 0.05), but no change in trefoil. In addition, self-reported worry related to vision (P < 0.001) and ability to perform activities (P < 0.001) significantly improved after surgery. The prevalence of double images, glare, halos, or starbursts decreased from 73% preoperatively to 56%, and no participants reported "very" or "extremely" bothersome visual symptoms after 12 months. Dry eye symptoms per Ocular Surface Disease Index score decreased significantly at 6 (P = 0.01) and 12 (P = 0.002) months after surgery. There was a 100% satisfaction rate with visual outcomes and duration of time to improvement in vision following the procedure. CONCLUSIONS: Although there was an increase in HOAs following topography-guided LASIK, there were significant improvements in the presence of double images, glare, halos, and starbursts and vision-related quality-of-life metrics. Overall satisfaction rates in this study were high.

MRI-Based Prediction of Clinical Improvement Following Ventricular Shunt Placement for Normal Pressure Hydrocephalus (NPH): Development and Evaluation of an Integrated Multi-Sequence Machine Learning Algorithm.

BACKGROUND AND PURPOSE: Symptoms of normal pressure hydrocephalus (NPH) are sometimes refractory to shunt placement, with limited ability to predict improvement for individual patients. We evaluated an MRI-based artificial intelligence method to predict post-shunt NPH symptom improvement. MATERIALS AND METHODS: NPH patients who underwent magnetic resonance imaging (MRI) prior to shunt placement at a single center (2014-2021) were identified. Twelve-month post-shunt improvement in modified Rankin Scale (mRS), incontinence, gait, and cognition were retrospectively abstracted from clinical documentation. 3D deep residual neural networks were built on skull stripped T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Predictions based on both sequences were fused by additional network layers. Patients from 2014-2019 were used for parameter optimization, while those from 2020-2021 were used for testing. Models were validated on an external validation dataset from a second institution (n=33). RESULTS: Of 249 patients, n=201 and n=185 were included in the T2-based and FLAIR-based models according to imaging availability. The combination of T2-weighted and FLAIR sequences offered the best performance in mRS and gait improvement predictions relative to models trained on imaging acquired using only one sequence, with AUROC values of 0.7395 [0.5765-0.9024] for mRS and 0.8816 [0.8030-0.9602] for gait. For urinary incontinence and cognition, combined model performances on predicting outcomes were similar to FLAIR-only performance, with AUROC values of 0.7874 [0.6845-0.8903] and 0.7230 [0.5600-0.8859]. CONCLUSIONS: Application of a combined algorithm using both T2-weighted and FLAIR sequences offered the best image-based prediction of post-shunt symptom improvement, particularly for gait and overall function in terms of mRS. ABBREVIATIONS: NPH = normal pressure hydrocephalus; iNPH = idiopathic NPH; sNPH = secondary NPH; AI = artificial intelligence; ML = machine learning; CSF = cerebrospinal fluid; AUROC = area under the receiver operating characteristic; FLAIR = fluid attenuated inversion recovery; BMI = body mass index; CCI = Charlson Comorbidity Index; SD = standard deviation; IQR = interquartile range.

Is Workload Associated With Oblique Injuries in Professional Baseball Players?

Background: Oblique strains have become a common injury among professional baseball players. The influence of player workload on oblique strains remains unknown. Purpose/Hypothesis: To determine whether workload is a risk factor for oblique strains in professional baseball players. We hypothesized that fewer days of rest, more innings pitched/fielded per game, and more batters faced/plate appearances per game would significantly increase a player's risk of sustaining an oblique strain. Study Design: Case-control study; Level of evidence, 3. Methods: All professional baseball players who sustained an oblique strain between 2011 and 2017 were identified using the Major League Baseball Health and Injury Tracking System. A separate dataset of player usage-days of rest per game, innings pitched or fielded per game, and batters faced or plate appearances per game-was used to determine the workload. We compared these usage variables between player games ≤2, ≤6, ≤12, and >12 weeks before a documented oblique strain with player games from a control group of players with no oblique strains. In a paired analysis, we compared acute (player games ≤2, ≤6, and ≤12 weeks preinjury) versus chronic (player games >12 weeks preinjury) workloads. Results: There were 311 oblique strains in pitchers and 392 oblique strains in position players during the study period. In pitchers, more innings pitched and more batters faced were associated with a subsequent oblique strain (P < .001 for all). In position players, fewer days of rest, more innings fielded, and more plate appearances were associated with a subsequent oblique strain (P < .001 for all). Pitchers who pitched ≥7 innings per game had a 2.4-fold (95% CI, 1.4-4.9) increased risk of subsequent oblique strain compared with those who pitched 1 inning per game. The percentage of position players with a subsequent oblique strain increased by 2.1-fold (95% CI, 1.3-3.5) with >4 plate appearances compared with 1 plate appearance per game. Conclusion: Our analysis demonstrated that workload was associated with an increased risk of sustaining an oblique injury in professional baseball players. High workload over time was more predictive of oblique strains compared to acute increases over chronic baseline workload.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

Performance and Return to Play After Surgery for Thoracic Outlet Syndrome in Professional Baseball Players: A Matched Cohort Analysis.

BACKGROUND: Thoracic outlet syndrome (TOS) remains a rare diagnosis but is being recognized as a cause of upper extremity dysfunction in professional baseball players. PURPOSE/HYPOTHESIS: The purpose was to determine performance and return-to-play (RTP) outcomes in professional baseball players after surgical treatment of TOS. The hypothesis was that there would be a high RTP rate in professional baseball players after TOS surgery with no statistical differences in performance between pitchers who had TOS surgery and matched controls. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All professional baseball players who underwent surgical treatment of TOS between 2010 and 2017 were identified using the Major League Baseball Health and Injury Tracking System database. Demographic and performance data (before and after surgery) for each player were recorded. Performance variables were then compared between players who underwent TOS surgery and matched controls. The matching criteria were no history of previous surgeries on affected arm, age at time of surgery, throwing side, level of play (Major or Minor League Baseball), and years of experience playing professional baseball. RESULTS: Overall, 52 players underwent surgery for TOS, of whom 46 (88%) were pitchers. The type of TOS was neurogenic in 69% and venous in 29%. One player had arterial TOS. After TOS surgery, 79% of players returned to play at the same or higher level (RTSP) by 9.5 months and played ≥3 years after surgery. No differences were found in RTSP rate based on the type of TOS. No statistical difference was found in RTP rates between major and minor league players. Pitchers had a 76% RTSP, which was similar to the natural attrition for control pitchers (P = .874). After TOS surgery, pitchers saw a decline in several performance metrics, but these declines were not different from those of control pitchers, indicating that the decline in performance after TOS surgery was no faster than is seen in healthy professional pitchers as they age. CONCLUSION: The rate of RTSP after surgery for TOS in professional baseball players was 79%. There was no difference in RTP based on the type of TOS. Pitchers who underwent surgery for TOS had no significant differences in pitching performance metrics after surgery compared with matched controls.

Safety and efficacy of liposomal irinotecan as the second-line treatment for advanced pancreatic cancer: A systematic review and meta-analysis.

INTRODUCTION: The use of nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and increased area under the concentration-time curve. However, comprehensive systematic reviews or meta-analyses evaluating its efficacy as a second-line treatment have been scarce. Therefore, this study aims to review the current body of evidence on nal-IRI, assessing its overall clinical performances regarding the disease. METHODS: A systemic literature search was conducted based on articles published before September 26, 2023 in PubMed, Cochrane Library, EMBASE, and Web of Science databases. The fixed effect model was performed to calculate pooled mean difference and odds ratio for essential outcomes, such as overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events. RESULTS: A total of 21 studies, including 3017 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, together with 5-fluorouracil and leucovorin, resulted in significantly improved PFS and OS, with a pooled mean difference of 1.01 months (95% confidence interval (95%CI)=0.97-1.05, p<0.01) and 0.29 months (95% CI=0.18-0.39, p<0.01) respectively; a pooled risk ratio of 2.06 (95%CI=1.30-3.27, p=0.002) for ORR compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted. CONCLUSION: Nal-IRI-based second-line treatments exhibited significantly improved PFS, OS and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.

Health Insurance and Access to Care in U.S. Working Age Adults Experiencing Long COVID.

INTRODUCTION: Long COVID encompasses a wide range of health problems that emerge, persist, or recur following acute COVID-19 illness. Given that the prevalence of self-reported Long COVID is highest among U.S. adults in their prime working years, it is important to identify unmet needs and gaps in healthcare access and coverage among working age adults. METHODS: Prevalences (95% CI) of health insurance coverage and access to care by Long COVID status were estimated among adults 18-64 years (n = 18,117), accounting for survey design and weighted to the U.S. non-institutionalized population in the 2022 National Health Interview Survey. Analyses were conducted in 2023. RESULTS: Overall, 3.7% (95% CI 3.4, 4.0) of respondents were experiencing Long COVID. Adults experiencing Long COVID were less likely to report being uninsured relative to adults not experiencing Long COVID (P=0.004); however, 49.0% (95% CI 43.2, 54.7) had high deductible health plans. Adjusting for sociodemographic characteristics, adults experiencing Long COVID were more likely to access healthcare compared to adults not experiencing Long COVID (P<0.01 for seeing a doctor, telemedicine appointments, ≥2 urgent care visits, ≥2 emergency department visits, and hospitalized overnight). Despite more frequent healthcare use, adults experiencing Long COVID were also more likely to abstain from and delay medical care, therapy, and prescriptions due to cost compared to adults not experiencing Long COVID (P<0.0001 for all comparisons). CONCLUSIONS: These findings may be used to inform healthcare planning for adults experiencing Long COVID and highlight the ongoing need to improve access and affordability of quality and comprehensive care.

Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN.

PURPOSE: Sequential PET/CT studies oncology patients can undergo during their treatment follow-up course is limited by radiation dosage. We propose an artificial intelligence (AI) tool to produce attenuation-corrected PET (AC-PET) images from non-attenuation-corrected PET (NAC-PET) images to reduce need for low-dose CT scans. METHODS: A deep learning algorithm based on 2D Pix-2-Pix generative adversarial network (GAN) architecture was developed from paired AC-PET and NAC-PET images. 18F-DCFPyL PSMA PET-CT studies from 302 prostate cancer patients, split into training, validation, and testing cohorts (n = 183, 60, 59, respectively). Models were trained with two normalization strategies: Standard Uptake Value (SUV)-based and SUV-Nyul-based. Scan-level performance was evaluated by normalized mean square error (NMSE), mean absolute error (MAE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). Lesion-level analysis was performed in regions-of-interest prospectively from nuclear medicine physicians. SUV metrics were evaluated using intraclass correlation coefficient (ICC), repeatability coefficient (RC), and linear mixed-effects modeling. RESULTS: Median NMSE, MAE, SSIM, and PSNR were 13.26%, 3.59%, 0.891, and 26.82, respectively, in the independent test cohort. ICC for SUVmax and SUVmean were 0.88 and 0.89, which indicated a high correlation between original and AI-generated quantitative imaging markers. Lesion location, density (Hounsfield units), and lesion uptake were all shown to impact relative error in generated SUV metrics (all p < 0.05). CONCLUSION: The Pix-2-Pix GAN model for generating AC-PET demonstrates SUV metrics that highly correlate with original images. AI-generated PET images show clinical potential for reducing the need for CT scans for attenuation correction while preserving quantitative markers and image quality.

Profile of Patients Receiving Computed Tomography Scans for Mild Traumatic Brain Injury in a Tertiary Care Hospital in Ethiopia.

BACKGROUND: Traumatic brain injury (TBI) is a leading contributor to emergency department (ED) mortalities in Ethiopia. Mild TBI patients comprise half of all TBI patients presenting for care in Ethiopia and have a high potential for recovery. As such, context-specific care-improving strategies may be highly impactful for this group of patients. OBJECTIVE: This study examines the presentation and disposition of mTBI patients who received a computed tomography scan of the head upon arrival at the largest teaching hospital in Ethiopia. METHODS: A retrospective cohort study was conducted from 2018 to2021 including patients >13 years old with a head injury and a Glasgow Coma Score of 13-15 who obtained a computed tomography scan of the head. Variables were collected from medical charts and single and multivariable analyses assessed outcomes of clinically important TBI (ciTBI) requiring a neurosurgical procedure or admission. RESULTS: A total of 193 patients were included. They were predominantly young men with no comorbidities, injured in road traffic accidents or by assault, had stable vital signs and were treated in lower-acuity ED areas. A minority demonstrated focal deficits, and 29.5% of patients had ciTBI. Most patients were discharged from the ED, but 13% were taken for operative neurosurgical procedures and 10.4% were admitted to the neurosurgery ward for observation. ED stays ranged from 8 hours to 10 days, as patients waited for CT availability, neurosurgical decision, or transportation. Female sex was independently protective of ciTBI. Self-referral status was independently protective against operative intervention. Female sex and self-referral status were independently protective of a disposition of admission and/or going to the operating room. CONCLUSIONS: This study characterizes the mTBI subgroup of head injury patients in Ethiopia's busiest ED: predominantly healthy young men with low-acuity presentations and only a fraction with abnormal neurological examinations. Nonetheless, about one-third had ciTBI and a minority were taken for neurosurgical procedures or admission, with female sex and self-referral identified as protective factors. Meanwhile, many patients stayed in the ED for days due to social or other nonmedical reasons. As TBI care in Ethiopia continues to improve, optimizing care for the mTBI subgroup is tantamount given their high recovery potential. This care will benefit from efficiently identifying those who need intervention or hospital level of care, and discharging those who do not.

Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

Impact of programmed cell death protein 1 inhibitor therapy on the survival of patients with advanced or recurrent uterine cancers: a meta-analysis.

Introduction: No prior meta-analysis has investigated the impact of programmed cell death protein 1 (PD-1) inhibitor therapy on survival outcomes in patients with advanced or recurrent uterine cancers (including both corpus and cervical cancers). Methods: A comprehensive search of PubMed and Embase databases was conducted, covering the past 10 years (up to August 2023) and encompassing all clinical research related to uterine cancer. Five randomized controlled trials and one cohort study met the inclusion criteria and were included in the meta-analysis. Data on patient demographics, clinical characteristics, treatment regimens, and survival outcomes were extracted. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as the relative risk of grade 3 or higher adverse events, were pooled using random-effects models. Results: Patients receiving PD-1 inhibitors had better OS (HR, 0.65, 95% CI, 0.59-0.72; P<.001) and PFS (HR, 0.59, 95% CI, 0.49-0.70; P<.001) than those receiving variable non-PD-1 inhibitor therapies among 3452 uterine cancer patients. The leave-one-out meta-analysis of the HR of OS showed no individual study impact on the estimation of the overall effect size. Subgroup analysis revealed better OS in the PD-1 inhibitors use than the controls in cervical cancer (HR, 0.68, 95% CI, 0.59-0.79), endometrial cancer (HR, 0.62, 95% CI, 0.54-0.72), and pembrolizumab use (HR, 0.66, 95% CI, 0.57-0.75) subgroups. Patients with advanced cervical cancer, who had CPS > 1, receiving PD-1 inhibitors have statistically significant benefits in OS compared to controls (HR, 0.65, 95% CI, 0.53-0.80). The pooled HR for overall survival was 0.71 (95% CI, 0.60-0.82; P<.001) in patients who received PD-1 inhibitors as compared to those who did not receive PD-1 inhibitors in proficient mismatch repair (MMR) endometrial cancer patients. However, in deficient MMR patients, the HR was 0.30 (95% CI, 0.13-0.70). The relative risk of grade 3 or higher adverse events was not higher in the PD-1 inhibitor group (relative risk, 1.12, 95% CI, 0.98-1.27). Conclusion: Survival was significantly better using PD-1 inhibitor therapy than variable non-PD-1 inhibitor chemotherapies among patients with advanced or recurrent uterine cancers.

Tooth Loss and Chronic Pain: A Population-based Analysis of the National Health and Nutrition Examination Survey.

Poor oral health conditions in adults are associated with chronic pain. A nationwide cross-sectional study was conducted to investigate the link between tooth loss and chronic pain. The study involved 8,662 participants from the National Health and Nutrition Examination Survey. Tooth count was categorized into 4 groups, and chronic pain was defined as persistent pain lasting over 3 months despite treatment. Location of the chronic pain, demographics, comorbidities, lifestyle determinants, and dietary intake were retrieved. Univariate and multivariate logistic regression were used to explore cross-sectional associations between tooth count and chronic pain. Compared to participants with more than 20 teeth, those with severe tooth loss presented greater odds of chronic pain (adjusted odds ratio [aOR] = 2.111, 95% confidence intervals (CI) = 1.213-3.676 for patients with 1-8 teeth). Edentulous participants presented with significantly higher odds of chronic pain in the lower extremities (78.4%) and buttocks (49.5%). In the multivariate model, apart from rheumatic arthritis (aOR = 4.004, 95% CI = 2.766-5.798), variables of higher chronic pain included smoking (aOR = 1.518, 95% CI = 1.228-1.878), and hypertension (aOR = 1.463, 95% CI = 1.013-2.112). On the contrary, being Mexican American (aOR = .603, 95% CI = .414-.880) was associated with lower odds of chronic pain. The findings suggested a significant link between chronic pain and tooth loss, independent of ethnicity, lifestyle determinants, and immune-mediated inflammatory diseases including rheumatoid arthritis. PERSPECTIVE: A U.S. nationwide study examined tooth loss and chronic pain. Those with severe tooth loss had increased odds of chronic pain. Edentulous individuals presented higher odds of pain in lower extremities and buttocks. This study highlighted the link between tooth loss and chronic pain, independent of comorbidities and lifestyle factors.

New-onset keratitis associated with epidermal growth factor receptor-based targeted therapies in Han Chinese patients with lung cancer: A multi-center cohort study.

PURPOSE: To determine the risk and incidence of keratitis following treatment with epidermal growth factor receptor inhibitors (EGFRi) and subtypes of EGFRi-associated keratitis. METHODS: This multi-center cohort study included EGFRi-treated patients and non-users with lung cancer between 2010 and 2023. EGFRi included first-generation agent gefitinib and erlotinib, second-generation agent afatinib, and third-generation agent osimertinib. The primary outcome was new-onset keratitis. Cox proportional hazard models with multivariable adjustment were applied to determine the effect of EGFRi on keratitis over time. Subgroup analyses were conducted, stratified by agents of EGFRi. Sub-outcome analyses were performed to identify the subtypes of EGFRi-associated keratitis. RESULTS: A total of 1549 EGFRi-treated patients and 6146 non-users were included. 38 (2.5%) EGFRi-treated patients developed keratitis. The incidence of keratitis in EGFRi-treated patients was significantly higher than that in controls (incidence rate, IR, per 1000 person-years = 14.7 vs 4.49, p < 0.0001). EGFRi-treated patients presented with an increased risk for keratitis (adjusted hazard ratio, aHR = 3.14, 95% CI = 1.85-5.35, p < 0.001). Erlotinib (aHR = 2.64, 95% CI = 1.35-5.15, p = 0.004), afatinib (aHR = 4.42, 95% CI = 2.17-9.02, p < 0.001), and osimertinib (aHR = 4.67, 95% CI = 1.60-13.64, p = 0.005), but not gefitinib (aHR = 2.30, 95% CI = 0.96-5.55, p = 0.063), significantly contributed to the risk of keratitis. Subtypes of EGFRi-associated keratitis included corneal ulcer (IR = 2.31 vs 0.166, p < 0.0001) and keratoconjunctivitis (IR = 9.27 vs 2.91, p < 0.0001). None of the EGFRi-treated patients developed perforated corneal ulcer, interstitial and deep keratitis, or corneal neovascularization. CONCLUSION: Treatment with EGFRi was associated with an increased risk of keratitis. Ocular toxicity of EGFRi was highest for third-generation agents, followed by second-generation agents, and then first-generation agents.