Comparative analysis of traditional machine learning and automated machine learning: advancing inverted papilloma versus associated squamous cell carcinoma diagnosis.

KEY POINTS: Inverted papilloma conversion to squamous cell carcinoma is not always easy to predict. AutoML requires much less technical knowledge and skill to use than traditional ML. AutoML surpassed the traditional ML algorithm in differentiating IP from IP-SCC.

Cardenolides in the defensive fluid of adult large milkweed bugs have differential potency on vertebrate and invertebrate predator Na+/K+-ATPases.

Aposematic animals rely on diverse secondary metabolites for defence. Various hypotheses, such as competition, life history and multifunctionality, have been posited to explain defence variability and diversity. We investigate the compound selectivity hypothesis using large milkweed bugs, Oncopeltus fasciatus, to determine if distinct cardenolides vary in toxicity to different predators. We quantify cardenolides in the bug's defensive secretions and body tissues and test the individual compounds against predator target sites, the Na+/K+-ATPases, that are predicted to differ in sensitivity. Frugoside, gofruside, glucopyranosyl frugoside and glucopyranosyl gofruside were the dominant cardenolides in the body tissues of the insects, whereas the two monoglycosidic cardenolides-frugoside and gofruside-were the most abundant in the defensive fluid. These monoglycosidic cardenolides were highly toxic (IC50 < 1 µM) to an invertebrate and a sensitive vertebrate enzyme, in comparison to the glucosylated compounds. Gofruside was the weakest inhibitor for a putatively resistant vertebrate predator. Glucopyranosyl calotropin, found in only 60% of bugs, was also an effective inhibitor of sensitive vertebrate enzymes. Our results suggest that the compounds sequestered by O. fasciatus probably provide consistency in protection against a range of predators and underscore the need to consider predator communities in prey defence evolution.

Importance of Baseline Fluorescein Angiography for Patients Presenting to Tertiary Uveitis Clinic.

PURPOSE: To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic. DESIGN: Retrospective comparison of diagnostic approaches. METHODS: Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by 3 uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering) and UWFFA (Optos Plc) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA compared with Set 1. RESULTS: The mean age of the patients was 46.9 ± 22.4 years (range, 7-96), and 91 (57.6%) were female. With Set 1 alone, 138 eyes (55.2%) were found to have active disease; localization was anterior in 58 eyes (42.0%), posterior in 53 eyes (38.4%), and anterior + posterior in 27 eyes (19.6%). With Set 2, 169 eyes of 107 patients had active anterior, posterior, or panuveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 eyes (18.3%) with active disease (P = .006) and an additional 31 eyes (18.3%) having disease in both anterior + posterior segments (P < .001). Regarding the primary outcome, management was changed in 68 eyes (27.4%) in Set 2 compared with Set 1. CONCLUSIONS: Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared with clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of patients with uveitis at the baseline visit.

A User-friendly Approach for the Diagnosis of Diabetic Retinopathy Using ChatGPT and Automated Machine Learning.

Purpose: To assess the capabilities of Chat Generative Pre-trained Transformer (ChatGPT) and Vertex AI in executing code-free preprocessing, training machine learning (ML) models, and analyzing the data. Design: Evaluation of diagnostic test or technology. Participants: ChatGPT and Vetrex AI as publicly available large language model and ML platform, respectively. Methods: ChatGPT was employed to improve the resolution of fundus photography images from the Methods to Evaluate Segmentation and Indexing Techniques in the field of Retinal Ophthalmology (Messidor-2) open-source dataset using the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique by Fiji software. Subsequently, Vertex AI, an automated ML (AutoML) platform, was utilized to develop 2 classification models. The first model served as a binary classifier for detecting the presence of diabetic retinopathy (DR), while the second determined its severity. Finally, ChatGPT was used to provide scripts for R and Python programming languages for data analysis and was also directly employed in analyzing the data in a code-free method. Main Outcome Measures: Evaluating the utility of ChatGPT in generating scripts for preprocessing images using Fiji and analyzing data across Python and R and assessing its potential in analyzing data through a code-free method. Investigating the capabilities of Vertex AI to train image classification models for detection of DR and its severity. Results: Two ML models were trained using 1740 images from the Messidor-2 database. The first model, designed to detect the severity of DR, achieved an area under the precision-recall curve (AUPRC) of 0.81, with a precision rate of 81.81% and recall of 72.83%. The second model, tailored for the detection of the presence of DR, recorded a precision and recall of 84.48% with an AUPRC of 0.90. Conclusions: ChatGPT and Vertex AI have the potential to enable physicians without coding expertise to preprocess images, analyze data, and train ML models. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Impact of first eye cataract surgery on falls among patients of advanced age: a comparative study.

OBJECTIVE: To compare the incidence of falls between patients with visually significant cataracts in both eyes and those who have undergone first-eye cataract surgery. METHODS: This retrospective case-control study involved patients with a history of cataracts in both eyes who had undergone first-eye cataract surgery within the past 9 to 12 months (pseudophakic group). The control group comprised patients with cataracts in both eyes (cataract group). We assessed best-corrected visual acuity (BCVA), systemic comorbidities and medications (using the Charlson comorbidity index), and independent daily activities (using the Lawton Instrumental Activities of Daily Living scale). The patients were questioned about experiencing two or more falls in the last 6 months. RESULTS: Each group comprised 50 patients. Binocular BCVA was significantly better in the pseudophakic group (0.05 ± 0.06 logMAR) than in the cataract group (0.77 ± 0.34 logMAR). Of all participants, 22% reported experiencing two or more falls in the last 6 months. Multivariate analysis demonstrated significantly better BCVA in participants with less than two falls. CONCLUSIONS: Patients of advanced age with visually significant cataracts in both eyes are at a higher risk of falling. First-eye cataract surgery may mitigate the occurrence of falls by improving binocular BCVA.

Recent advances in uveitis therapy: focus on selected phase 2 and 3 clinical trials.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Investigating the safety and efficacy of nerve stimulation for management of groin pain after surgical herniorrhaphy: a systematic review and meta-analysis.

PURPOSE: Chronic post-operative inguinal pain (CPIP) following inguinal hernia repair has been a major sequela affecting 4000-48000 patients annually. Optimal management of CPIP has been a challenge, and pharmacological management particularly with opioids has shown unsatisfactory results. The main objective of this systematic review is to investigate the safety and efficacy of neuromodulation as an alternative intervention for the management of post-operative inguinal pain. METHODS: A literature search was conducted by three reviewers to identify all relevant studies on the use of neuromodulatory interventions for treating post-operative inguinal pain. Data on study characteristics, neuromodulatory modalities, and patient's clinical data such as pre/post-interventional pain scores and analgesic requirements were extracted and reported. RESULTS: A total of 389 patients with 357 (95.9%) males and 15 (4.1%) females were evaluated. The mean age of study participants was 47.9 ± 10.4 years. There were 187 (48.1%) and 202 (51.9%) patients allocated to the control and trial groups, respectively. The most common neuromodulation modality was TENS (4, 36.4%), followed by SCS (3, 27.3%), PNS (3, 27.3%), and acupuncture-assisted (2, 18.2%). The overall mean follow-up duration of the entire cohort was 3.8 months. The mean difference between pre-operative and post-operative VAS scores in the trial groups was 4.65 (95% Confidence Interval [CI], 2.97, 6.33), which was statistically significant (P value < 0.05). Patient-reported outcome measures showed significant responsiveness toward their treatments. CONCLUSION: Nerve stimulation, in its many forms, is a safe and feasible option for the management of post-operative inguinal pain.

Comparative real-time PCR quantification of cytomegalovirus in severe early childhood caries and caries-free children.

PURPOSE: The present study was undertaken to evaluate cytomegalovirus (CMV) load in carious lesions in children with severe early childhood caries (S-ECC) and compare it with caries-free (CF), healthy children, by quantitative real-time polymerase chain reaction (PCR). MATERIALS AND METHODS: Dental plaque samples were collected from 57 subjects including S-ECC (n = 33) and CF (n = 24) patients. The two groups were matched in terms of age, gender, and socioeconomic status. After deoxyribonucleic acid (DNA) extraction, SYBR Green real-time PCR was used to quantify CMV DNA. RESULTS: The CMV DNA was detected in seven patients in the S-ECC group. The mean of decayed, missing, and filled tooth surfaces (dmfs) was 11.90 ± 5.95 in the S-ECC group. There was no significant difference in gender between the two groups. There was a significant relationship between CMV positivity in children and the S-ECC group (p = 0.043). CONCLUSION: Results of this study suggest a relationship between the presence of CMV in the oral cavity and S-ECC. We can design clinical trials to confirm these results and improve children's dental care.

Tomographic phase and attenuation extraction for a sample composed of unknown materials using x-ray propagation-based phase-contrast imaging.

Propagation-based phase-contrast x-ray imaging (PB-PCXI) generates image contrast by utilizing sample-imposed phase-shifts. This has proven useful when imaging weakly attenuating samples, as conventional attenuation-based imaging does not always provide adequate contrast. We present a PB-PCXI algorithm capable of extracting the x-ray attenuation  ß and refraction  δ, components of the complex refractive index of distinct materials within an unknown sample. The method involves curve fitting an error-function-based model to a phase-retrieved interface in a PB-PCXI tomographic reconstruction, which is obtained when Paganin-type phase retrieval is applied with incorrect values of δ and ß. The fit parameters can then be used to calculate true δ and ß values for composite materials. This approach requires no a priori sample information, making it broadly applicable. Our PB-PCXI reconstruction is single-distance, requiring only one exposure per tomographic angle, which is important for radiosensitive samples. We apply this approach to a breast-tissue sample, recovering the refraction component  Î´, with 0.6-2.4% accuracy compared with theoretical values.

Vestibular evaluation following cochlear implantation in patients with inner-ear anomalies.

OBJECTIVE: This cross-sectional study investigated vestibular function outcomes after cochlear implantation in patients with inner-ear anomalies. METHODS: Twenty-two patients with bilateral symmetric inner-ear anomalies and 28 patients with normal inner ears were included. All were congenitally or progressively deaf persons implanted unilaterally during the previous 15 years. Vestibular system function was assessed by vestibular-evoked myogenic potential and bithermal caloric tests. RESULTS: The vestibular-evoked myogenic potential abnormality rate in implanted ears with an inner-ear anomaly was 81.8 per cent, compared with 39.3 per cent in implanted ears with normal anatomy. In the non-implanted sides, the rate was 45.5 per cent (10 out of 22 cases) in the inner-ear anomaly patients compared with 17.9 per cent in patients with normal inner-ear structure. The respective abnormal caloric test rates in inner-ear anomaly versus normal anatomy patients were 81.8 per cent and 17.9 per cent (implanted ears), 77.3 per cent and 14.3 per cent (non-implanted sides). CONCLUSION: Inner-ear anomaly and implantation were both associated with more vestibular-evoked myogenic potential abnormalities; when occurring together, these factors showed a synergistic effect. Caloric test abnormality is mainly dependent on the presence of an inner-ear anomaly, but implantation is not associated with caloric abnormality.

Intravitreal Methotrexate.

Intravitreal methotrexate (MTX) has been proven to be an effective treatment for various intraocular diseases. In this article, a comprehensive review was performed on intravitreal applications of methotrexate. Different aspects of the administration of intravitreal MTX for various clinical conditions such as intraocular tumors, proliferative vitreoretinopathy, diabetic retinopathy, age-related macular degeneration, and uveitis were reviewed and the adverse effects of intravitreal injection of MTX were discussed. The most common indications are intraocular lymphoma and uveitis. Other applications remain challenging and more studies are needed to establish the role of intravitreal MTX in the management of ocular diseases.

Isolated Intraconal Meningioma.

PURPOSE: To report a rare case of isolated intraconal meningioma. CASE REPORT: A 24-year-old woman presented with painless proptosis in her left eye which started and progressed during her pregnancy about 10 months ago. Hertel exophthalomometry revealed anterior displacement of the globe with 4 mm of proptosis which was remarkable. Magnetic resonance imaging (MRI) demonstrated an intraconal circumscribed oval-shaped mass with hypointense signals on T1-weighted images and hyperintense signals on T2-weighted images, mimicking cavernous hemangioma. This mass, however, was free of any connections to optic nerve or bones. Due to the imaging characteristics, more prevalent diagnoses like cavernous hemangioma were placed on the top of the differential diagnoses list. However, during the surgical excision, the tumor's consistency and gross features were not compatible with cavernous hemangioma. The pathologic findings instead determined meningotheliomatous meningioma, a very rare condition, which was far from our expectations prior to the surgery. CONCLUSION: Ectopic orbital meningiomas are rare tumors that are not easily diagnosed without postoperative histopathology. Despite its low prevalence, they should be considered in the differential diagnosis list of intraconal masses with hypointense signals on T1-weighted images and hyperintense signals on T2-weighted images.

Management of refractory Acanthamoeba keratitis, two cases.

Acanthamoeba keratitis is a serious infection of the eye that can result in permanent visual impairment or blindness, caused by free-living amoebae of the genus Acanthamoeba. Early diagnosis is necessary for effective treatment of Acanthamoeba keratitis. Acanthamoeba is abundant in nature and can be found in water, soil, and air. Acanthamoeba keratitis is usually diagnosed by culture from a scraping of the eye or by confocal microscopy. In this paper, two complicated Acanthamoeba keratitis cases are reported.

Infectious keratitis: trends in microbiological and antibiotic sensitivity patterns.

OBJECTIVES: To report the spectrum and trends of isolated microorganisms and their antibiotic susceptibility profile in patients with infectious keratitis in a 6-year period at a referral centre in Tehran. METHODS: The microbiology records of all corneal scrapings with a diagnosis of infectious keratitis were reviewed. RESULTS: A total of 6282 corneal scrapings were performed during the study period, of which 2479 (39.5%) samples were culture positive. Pseudomonas aeruginosa was found to be the most common causative agent in patients with keratitis, although Streptococcus pneumonia was the most prevalently isolated microorganism in patients older than 50 years. Fusarium sp. was the most common responsible pathogen in patients with fungal keratitis. The prevalence of bacterial keratitis due to gram positive microorganisms increased over time, however the number of Pseudomonas keratitis decreased in the second half of the study. Gram negative organisms showed a good sensitivity to levofloxacin, however, 34.1% of S. aureus isolates and 29.7% of coagulase negative staphylococci were resistant to this antibiotic. The odds of ciprofloxacin and levofloxacin resistance increased 1.25 and 1.15 for each 1-year increase in culture date, respectively (P < 0.001, P = 0.004). CONCLUSIONS: We documented an increasing trend in the percentage of gram positive bacteria. Levofloxacin monotherapy might still be a good option in patients with gram negative bacterial keratitis, however owing to increasing resistance of staphylococci to fluoroquinolones, a regimen consisting of a combination of fortified antibiotics may be more effective in staphylococcal keratitis.

Curcumin-gold-polyethylene glycol nanoparticles as a nanosensitizer for photothermal and sonodynamic therapies: In vitro and animal model studies.

Photothermal and ultrasound therapies are novel non-invasive strategies for tumor treatment which are equipped with a photosensitizer and sonosensitizer subsequent activation by laser irradiation and ultrasound exposure. In this study, curcumin-gold-polyethylene glycol nanoparticles (Cur-Au NPs-PEG) were synthesized, and the dual role in photothermal (PTT) and sonodynamic (SDT) therapies of melanoma cancer was evaluated. The toxicity effect of Cur-Au NPs-PEG against a mouse malignant melanoma cell line C540 (B16/F10) was firstly inspected in vitro. Cur-Au NPs-PEG provided a hyperthermal microenvironment and generated reactive oxygen species upon PTT and STD, respectively, with representing synergism effects. Studies in vivo in a tumor-bearing animal also demonstrate the superiority of PTT and SDT in destroying melanoma tumor.

Hemolytic disease of the fetus and newborn caused by anti-Hr0 in a 27-year-old female with Dc- phenotype: A case report.

Anti-Hr0 (Anti-Rh17) is a rare immune Immunoglobulin G (IgG) to high-frequency Rh antigens that may cause severe and often fatal Hemolytic disease of the fetus and newborn (HDFN) in D--, Dc- and DCw- mothers who have been exposed to red cells of the common Rh phenotype by transfusion or pregnancy. Several pregnant women have been affected by this antibody leading to perinatal death. Therefore, immediate and effective management of these cases is of great importance. We report a case of HDFN in a 27-year-old (G5, P3, L1), woman with Rh Dc- phenotype managed successfully using intravenous immunoglobulin (IVIg) and simple transfusions.

Longitudinal Epithelial Thickness Profile Changes 18 Months After Photorefractive Keratectomy.

PURPOSE: Long-term evaluation of corneal epithelial thickness (ET) profile changes after photorefractive keratectomy (PRK) using Fourier-domain anterior segment optical coherence tomography. METHODS: Three hundred twenty-six eyes of 163 patients were included in this prospective observational study. The corneal epithelial map was obtained across a 9-mm diameter area of the cornea before and up to 27 months after surgery. ET was assessed in 25 sectors and 4 annular zones (central 2 mm, paracentral 2-5 mm, midperipheral 5-7 mm, and peripheral 7-9 mm). RESULTS: There was a significant reduction in mean ET in all zones 1 month after PRK. Subsequently, ET increased in all annular zones. The change in mean ET became stable in the midperipheral and peripheral zones at 3 to 6 months and in the central zone at 12 months, and it continued to increase in the paracentral zone even after 18 months after surgery. The ET was 3.40 µm and 4.05 µm in the central and paracentral zones at 6 months, respectively. Postoperative spherical equivalent changed significantly only from 1 to 3 months (P < 0.04). There was a significant correlation between postoperative spherical equivalent at month 1 and ET change in the paracentral and midperipheral zones (P < 0.027). CONCLUSIONS: There is a significant reduction in ET 1 month after myopic PRK with a gradual thickening thereafter until it reaches stability at 12 months in the central zone. However, it continues to change even after 18 months in the paracentral zone. The greatest thickening is in the paracentral zone, followed by the central zone.