ABSTRACT
Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor2-negative breast cancer (HR+/HER2- BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2- BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Immunoconjugates , Lung Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Immunoconjugates/adverse effects , Trastuzumab , Receptor, ErbB-2 , Camptothecin , Clinical Trials, Phase I as TopicABSTRACT
OBJECTIVE: To compare results of simulator-based vs traditional training of medical students in direct ophthalmoscopy. DESIGN: Randomized controlled trial. METHODS: First-year medical student volunteers completed 1 hour of didactic instruction regarding direct ophthalmoscopes, fundus anatomy, and signs of disease. Students were randomized to an additional hour of training on a direct ophthalmoscope simulator (n = 17) or supervised practice examining classmates (traditional method, n = 16). After 1 week of independent student practice using assigned training methods, masked ophthalmologist observers assessed student ophthalmoscopy skills (technique, efficiency, and global performance) during examination of 5 patient volunteers, using 5-point Likert scales. Students recorded findings and lesion location for each patient. Two masked ophthalmologists graded answer sheets independently using 3-point scales. Students completed surveys before randomization and after assessments. Training groups were compared for grades, observer- and patient-assigned scores, and survey responses. RESULTS: The simulator group reported longer practice times than the traditional group (P = .002). Observers assigned higher technique scores to the simulator group after adjustment for practice time (P = .034). Combined grades (maximum points = 20) were higher for the simulator group (median: 5.0, range: 0.0-11.0) than for the traditional group (median: 4.0, range: 0.0-9.0), although the difference was not significant. The simulator group was less likely to mistake the location of a macular scar in 1 patient (odds ratio: 0.28, 95% confidence interval: 0.056-1.35, P = .013). CONCLUSIONS: Direct ophthalmoscopy is difficult, regardless of training technique, but simulator-based training has apparent advantages, including improved technique, the ability to localize fundus lesions, and a fostering of interest in learning ophthalmoscopy, reflected by increased practice time.
Subject(s)
Students, Medical , Clinical Competence , Fundus Oculi , Humans , Ophthalmoscopy/methods , Prospective Studies , TeachingABSTRACT
PURPOSE: To evaluate the effect of brimonidine tartrate 0.025% ophthalmic solution on pupil size under scotopic conditions in healthy adults METHODS: Pupil size was measured in 56 eyes of 28 volunteer participants using a pupillometer under scotopic conditions. Age, gender, and iris color were recorded. Subjects using any ophthalmic medications other than artificial tears were excluded. The pupil size was subsequently measured again under scotopic conditions 60 min after instillation of brimonidine tartrate 0.025% ophthalmic solution. RESULTS: Statistically significant miosis was seen after instillation of brimonidine tartrate 0.025% (p = 0.04). Average pupil size prior to brimonidine 0.025% instillation was 7.28 ± 1.05 mm, and average pupil size after instillation of brimonidine 0.025% was 6.36 ± 1.68 mm, a reduction of - 23.7% in pupil area. Subjects with light irides demonstrated a greater miotic effect than subjects with dark irides (1.55 mm vs. 0.67 mm, p < 0.0001), with a pupil area reduction of - 37.6% and - 17.4%, respectively. The amount of miosis was independent of initial pupil size. CONCLUSIONS: Brimonidine tartrate 0.025% causes significant miosis in scotopic settings, although the effect is not as great in darker colored eyes. Further studies are needed to determine the latency and duration of the effect and whether the amount of miosis is clinically significant.
Subject(s)
Pupil , Quinoxalines , Adult , Brimonidine Tartrate , Humans , Lubricant Eye Drops , Miotics , Ophthalmic SolutionsABSTRACT
PURPOSE: To report complications of cosmetic artificial iris implantation and explantation outcomes. DESIGN: Retrospective case series. METHODS: Medical records of 12 patients (24 eyes) who presented to us after being implanted with cosmetic artificial irises elsewhere were reviewed. Data collected included baseline demographics, presenting symptoms, examination findings, and management outcomes. RESULTS: Eight eyes had NewColorIris implants and 16 had BrightOcular implants. The mean interval from cosmetic iris implantation to presentation was 61.7 ± 60.0 months. The mean follow-up after explantation was 35.5 ± 38.1 months. Complications at presentation included iris abnormalities (11 eyes, 45.8%), elevated intraocular pressure (8 eyes, 33.3%), corneal edema (6 eyes, 25%), intraocular inflammation (5 eyes, 20.8%), and cataract (4 eyes, 16.7%). Surgical interventions included cosmetic iris removal (19 eyes, 79.2%), cataract extraction (7 eyes, 29.2%), corneal transplantation (7 eyes, 29.2%), and glaucoma surgery (4 eyes, 16.7%). Complications at the last follow-up examination included native iris defects (11 eyes, 45.8%), persistent glaucoma (7 eyes, 29.2%), cataract (5 eyes, 20.8%), corneal edema (4 eyes, 16.7%), and intraocular inflammation (2 eyes, 8.3%). The mean logarithm of the minimum angle of resolution was 0.56 ± 0.47 at presentation and 0.78 ± 0.88 at the last examination (P = .30). The mean intraocular pressure was 22.7 ± 15.8 mm Hg at presentation and 13.4 ± 6.99 mm Hg at the last examination (P = .02). CONCLUSION: Cosmetic iris implantation was associated with serious complications at the time of presentation, and adverse sequelae persisted for years after explantation.
Subject(s)
Artificial Organs , Device Removal , Iris , Postoperative Complications , Prosthesis Implantation/adverse effects , Surgery, Plastic/adverse effects , Adult , Corneal Edema/etiology , Endophthalmitis/etiology , Female , Follow-Up Studies , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Ocular Hypertension/etiology , Retrospective Studies , Visual Acuity/physiologyABSTRACT
BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is characterized by a congenital triad of keratitis, ichthyosis, and deafness, and is most commonly associated with mutations in the gap junction protein beta 2 gene (GJB2) on chromosome 13q11-q12. METHODS: Multimodal anterior segment imaging and genetic testing were used to supplement clinical examination findings in the diagnosis and management of a 12-year-old boy with suspected KID syndrome. RESULTS: The patient presented with hearing loss, ichthyosis of the face and extremities, and corneal scarring and keratinization. The corneal limbal stem cell population was found to be normal on in vivo confocal microscopy, whereas the basal epithelium of the cornea demonstrated scarring and areas of cellular loss. Screening of GJB2 revealed a presumed pathogenic heterozygous missense mutation, c.148G>A, confirming the diagnosis of KID syndrome. CONCLUSIONS: Multimodal imaging including in vivo confocal microscopy suggests that dysfunctional corneal basal epithelium maturation might contribute to the pathophysiology of keratopathy in KID syndrome.
Subject(s)
Cornea/pathology , Keratitis/diagnosis , Microscopy, Confocal/methods , Multimodal Imaging , Tomography, Optical Coherence/methods , Child , Humans , MaleABSTRACT
Patient satisfaction after modern day cataract surgery requires excellent surgical technique but increasingly demands superior refractive outcomes as well. In many cases, there exists an expectation from patients, as well as surgeons, to achieve emmetropia after cataract surgery. This is particularly true in patients electing premium intraocular lens technology to correct astigmatism and presbyopia to minimize spectacle dependence. Despite continued advances in preoperative and intraoperative diagnostics, refractive planning, and surgical technology, residual refractive error remains a primary source of dissatisfaction after cataract surgery. The need to enhance refractive outcomes and treat residual astigmatic or spherical refractive errors postoperatively becomes paramount to meeting the expectations of patients in their surgical outcome. This article reviews the potential preoperative and intraoperative pitfalls that can be the source of refractive error, the various options to enhance refractive outcomes, and potential future technologies to limit residual refractive error after cataract surgery.
Subject(s)
Astigmatism , Cataract Extraction , Cataract , Lenses, Intraocular , Refractive Errors , Astigmatism/etiology , Astigmatism/prevention & control , Astigmatism/surgery , Humans , Lens Implantation, Intraocular , Refractive Errors/etiologyABSTRACT
BACKGROUND: Anterior segment optical coherence tomography (AS OCT) is a helpful tool used to diagnose and manage many corneal conditions, but its use has not been reported in case of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS OCT findings in cases of PUK. METHODS: Retrospective observational case series of six eyes presenting with a PUK and proven systemic vasculitis. Clinical course, slit lamp photographs, and AS OCT findings were the main outcomes. RESULTS: The AS OCT findings were found to correlate with the ocular disease's level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed. The mean total corneal thickness at last follow-up was significantly thicker (509 ± 147 µm) compared with the mean corneal thickness at onset (408 ± 131 µm; P = 0.03). CONCLUSIONS: AS OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.
Subject(s)
Anterior Eye Segment/diagnostic imaging , Corneal Stroma/diagnostic imaging , Corneal Ulcer/diagnostic imaging , Epithelium, Corneal/diagnostic imaging , Tomography, Optical Coherence , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Corneal Stroma/pathology , Corneal Ulcer/drug therapy , Drug Therapy, Combination , Epithelium, Corneal/pathology , Female , Follow-Up Studies , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Retrospective Studies , Slit Lamp MicroscopyABSTRACT
We report a method for sensing analytes in tear-fluid using commercial contact lenses (CLs) as sample collectors for subsequent analysis with a cost-effective and field-portable reader. In this study we quantify lysozyme, the most prevalent protein in tear fluid, non-specifically bound to CLs worn by human participants. Our mobile reader uses time-lapse imaging to capture an increasing fluorescent signal in a standard well-plate, the rate-of-change of which is used to indirectly infer lysozyme concentration through the use of a standard curve. We empirically determined the best-suited CL material for our sampling procedure and assay, and subsequently monitored the lysozyme levels of nine healthy human participants over a two-week period. Of these participants who were regular CL wearers (6 out of 9), we observed an increase in lysozyme levels from 6.89 ± 2.02 µg mL-1 to 10.72 ± 3.22 µg mL-1 (mean ± SD) when inducing an instance of digital eye-strain by asking them to play a game on their mobile-phones during the CL wear-duration. We also observed a lower mean lysozyme concentration (2.43 ± 1.66 µg mL-1) in a patient cohort with dry eye disease (DED) as compared to the average monitoring level of healthy (no DED) human participants (6.89 ± 2.02 µg mL-1). Taken together, this study demonstrates tear-fluid analysis with simple and non-invasive sampling steps along with a rapid, easy-to-use, and cost-effective measurement system, ultimately indicating physiological differences in human participants. We believe this method could be used in future tear-fluid studies, even supporting multiplexed detection of a panel of tear biomarkers toward improved diagnostics and prognostics as well as personalized mobile-health applications.
Subject(s)
Contact Lenses, Hydrophilic , Dry Eye Syndromes , Antiviral Agents , Humans , Muramidase , TearsABSTRACT
Various machine learning techniques have been developed for keratoconus detection and refractive surgery screening. These techniques utilize inputs from a range of corneal imaging devices and are built with automated decision trees, support vector machines, and various types of neural networks. In general, these techniques demonstrate very good differentiation of normal and keratoconic eyes, as well as good differentiation of normal and form fruste keratoconus. However, it is difficult to directly compare these studies, as keratoconus represents a wide spectrum of disease. More importantly, no public dataset exists for research purposes. Despite these challenges, machine learning in keratoconus detection and refractive surgery screening is a burgeoning field of study, with significant potential for continued advancement as imaging devices and techniques become more sophisticated.
Subject(s)
Diagnosis, Computer-Assisted/methods , Keratoconus/diagnosis , Machine Learning , Mass Screening/methods , Refractive Surgical Procedures , Humans , Patient SelectionABSTRACT
Salzmann's nodular degeneration (SND) typically occurs in patients who are female, 50-60 years old, and have a history of corneal inflammation and irritation. Multiple case reports have documented associations between SND and trachoma, viral infections, trauma, contact lens wear, corneal surgeries and corneal exposure. The authors describe a patient with bilateral SND confirmed by anterior segment optical coherence tomography (OCT) imaging in the context of thyroid eye disease (TED) and history of LASIK. Treatment involved propylthiouracil (PTU), artificial tear use, loteprednol etabonate ophthalmic gel, eyelid taping and selenium supplementation and prospective superficial keratectomy with diamond burr polish.
Subject(s)
Corneal Dystrophies, Hereditary/etiology , Graves Ophthalmopathy/complications , Limbus Corneae/pathology , Adult , Corneal Dystrophies, Hereditary/diagnostic imaging , Corneal Dystrophies, Hereditary/physiopathology , Corneal Topography , Female , Graves Ophthalmopathy/diagnosis , Humans , Limbus Corneae/diagnostic imaging , Prospective Studies , Slit Lamp , Tomography, Optical Coherence , Vision Disorders/diagnosis , Vision Disorders/etiology , Vision Disorders/physiopathology , Visual Acuity/physiologyABSTRACT
As cataract surgery continues to evolve, the intraoperative small pupil continues to pose challenges to even the most experienced cataract surgeon. Several steps can be taken preoperatively to decrease the chance of intraoperative miosis. Even so, the problem of miosis during cataract surgery remains a relatively common occurrence. This paper discusses many steps, both preoperative and intraoperative, that can make surgery technically easier and safer, thus maximizing the postoperative outcomes and patient satisfaction. Complications associated with small-pupil cataract surgery, risk factors for intraoperative miosis, the preoperative and intraoperative management of the small pupil during cataract surgery, and postoperative care are reviewed.
Subject(s)
Cataract Extraction/methods , Cataract/complications , Miosis/surgery , Humans , Intraoperative Complications/prevention & control , Mydriatics/therapeutic useABSTRACT
An 86-year-old woman underwent penetrating keratoplasty for pseudophakic bullous keratopathy and presented with an acute corneal ulcer thereafter. Examination demonstrated a fluffy white infiltrate and epithelial defect with subsequent endothelial plaque formation and anterior chamber inflammation. The ulcer was cultured, and fortified topical vancomycin and tobramycin were initiated but failed to significantly improve the clinical course. Cultures were ultimately positive for fungus Microcyclosporella mali that responded well to topical natamycin with stabilisation of the ulcer after 6â weeks of topical therapy. This is the first reported case of fungal keratitis due to M. mali.