Assessing the Impact of Image Quality on Deep Learning Classification of Infectious Keratitis.

Objective: To investigate the impact of corneal photograph quality on convolutional neural network (CNN) predictions. Design: A CNN trained to classify bacterial and fungal keratitis was evaluated using photographs of ulcers labeled according to 5 corneal image quality parameters: eccentric gaze direction, abnormal eyelid position, over/under-exposure, inadequate focus, and malpositioned light reflection. Participants: All eligible subjects with culture and stain-proven bacterial and/or fungal ulcers presenting to Aravind Eye Hospital in Madurai, India, between January 1, 2021 and December 31, 2021. Methods: Convolutional neural network classification performance was compared for each quality parameter, and gradient class activation heatmaps were generated to visualize regions of highest influence on CNN predictions. Main Outcome Measures: Area under the receiver operating characteristic and precision recall curves were calculated to quantify model performance. Bootstrapped confidence intervals were used for statistical comparisons. Logistic loss was calculated to measure individual prediction accuracy. Results: Individual presence of either light reflection or eyelids obscuring the corneal surface was associated with significantly higher CNN performance. No other quality parameter significantly influenced CNN performance. Qualitative review of gradient class activation heatmaps generally revealed the infiltrate as having the highest diagnostic relevance. Conclusions: The CNN demonstrated expert-level performance regardless of image quality. Future studies may investigate use of smartphone cameras and image sets with greater variance in image quality to further explore the influence of these parameters on model performance. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Alternaria fungus growing on top of cyanoacrylate glue in a patient with perforated corneal ulcer.

Purpose: To demonstrate a case where Alternaria fungus grew on top of cyanoacrylate glue used to seal a perforated corneal ulcer. Observations: We document the clinical course of a rare case of Alternaria keratitis over the course of 6 months. Despite the purported antifungal properties of cyanoacrylate glue demonstrated in vitro, this case provides in vivo evidence that this substance can serve as a scaffold on which pathogenic fungi may grow. Conclusion: This report demonstrates the importance of close follow up of patients with corneal glue patches in place. Ophthalmologists should continue to inspect the cornea and glue for possible development of secondary infection, particularly with concomitant contact lens and/or steroid use.

Hawai'i Rural Health Program: Shaping the Next Generation of Rural Doctors.

Like many areas of the United States, Hawai'i and its rural communities are suffering from a significant physician shortage. The University of Hawai'i (UH) John A. Burns School of Medicine (JABSOM) developed the Hawai'i Rural Health Program (HRHP) in 2011 to help provide early and substantial rural training experiences for its medical students in hopes of generating more rural health care providers. Thus far, 20.6% of the students who participated in this program and have since graduated from residency are now practicing in rural communities. Final exam grades of students who participated in the program were not statistically different from those who did not participate, suggesting a similar quality of training between both the rural and traditional cohorts of students. Reflections from students who completed the program demonstrate the large and lasting impact that this immersive experience has on their medical education and desire to help rural communities.

Neurotrophic keratopathy: current challenges and future prospects.

Neurotrophic keratopathy (NK), or neurotrophic keratitis, is a degenerative condition that results from decreased innervation to the cornea. The cornea is innervated by the ophthalmic branch of the trigeminal nerve. Neurotrophic keratopathy is most commonly caused by herpes keratitis however, any condition that disrupts the normal corneal innervation can cause NK. Neurotrophic keratopathy is a clinical diagnosis and is classified into three stages based on the disease severity. Stage 1 has mild epithelial defects, such as punctate keratopathy, stage 2 disease has persistent epithelial defects, and stage 3 is defined by the presence of ulcers. Current treatment modalities consist of medical and surgical options. Stage 1 is treated with lubrication through artificial tears, eyelid taping, and punctal plug/cautery. Stage 2 treatment can involve therapeutic contact lenses, topical autologous or allogenic serum, tarsorrhaphy, botulinum toxin injections, and possibly anti-inflammatory medications. Stage 3 disease may require human nerve growth factor, amniotic membrane transplantation, conjunctival flap, or corneal neurotization. New therapies, such as matrix regenerating therapy, plasma rich in growth factors, Thymosin ß4, Substance P/Insulin like growth factor-1, and nicergoline represent exciting future options.KEY MESSAGESNeurotrophic keratopathy is a rare degenerative disease defined by decreased innervation to the cornea that is associated with significant morbidity.Treatment options range from lubrication alone to various medical and surgical treatments.Matrix regenerating therapy, plasma rich in growth factors, Thymosin ß4, Substance P/Insulin like growth factor-1, and nicergoline are exciting novel therapies that will influence how neurotrophic keratopathy is treated in the future.

ACCELERATE: A Patient-Powered Natural History Study Design Enabling Clinical and Therapeutic Discoveries in a Rare Disorder.

Geographically dispersed patients, inconsistent treatment tracking, and limited infrastructure slow research for many orphan diseases. We assess the feasibility of a patient-powered study design to overcome these challenges for Castleman disease, a rare hematologic disorder. Here, we report initial results from the ACCELERATE natural history registry. ACCELERATE includes a traditional physician-reported arm and a patient-powered arm, which enables patients to directly contribute medical data and biospecimens. This study design enables successful enrollment, with the 5-year minimum enrollment goal being met in 2 years. A median of 683 clinical, laboratory, and imaging data elements are captured per patient in the patient-powered arm compared with 37 in the physician-reported arm. These data reveal subgrouping characteristics, identify off-label treatments, support treatment guidelines, and are used in 17 clinical and translational studies. This feasibility study demonstrates that the direct-to-patient design is effective for collecting natural history data and biospecimens, tracking therapies, and providing critical research infrastructure.

Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review.

The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA . Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols.

Migraine Headache Treated with Famciclovir and Celecoxib: A Case Report.

INTRODUCTION: Herpes simplex virus (HSV) has been speculated to play a role in migraine headache pathophysiology. We present the first successful migraine headache treatment with therapy specifically targeting HSV infection. CASE PRESENTATION: A previously healthy 21-year-old white woman presented with a severe headache and was diagnosed with severe migraine headache disorder. She initially was treated with standard migraine headache medications without symptomatic improvement. She was then given famciclovir and celecoxib. The patient fully recovered within days and continues to enjoy significant reduction in severity and frequency of symptoms. DISCUSSION: Famciclovir and celecoxib may work synergistically against HSV. The virus may play a role in the pathophysiology of migraine headaches, and this is the first case report of successful migraine headache treatment with these medications. Further studies are needed to elucidate the efficacy of these medications in treating migraine disorder.