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Introduction: Antibody-drug conjugates (ADCs) are increasingly utilized in patients with solid tumors and hematologic malignancies. However, the adverse ocular toxicity induced by ADCs has not been comprehensively evaluated in real-world clinical settings. Methods: Data from April 2019 to March 2024 based on the FDA Adverse Event Reporting System (FAERS) were extracted and analyzed. Disproportionality analysis was used to evaluate the association between ADCs and ocular adverse events (AEs). The median time to onset (TTO) of various ADCs was compared. Results: A comprehensive analysis identified 2,686 ocular AEs associated with ADCs. Among these, Tisotumab vedotin had the most positive signals at the preferred terms (PTs) level, followed by trastuzumab emtansine and enfortumab vedotin. In contrast, gemtuzumab ozogamicin demonstrated minimal ocular toxicity signals. Cluster analysis revealed that ADC-related ocular toxicities predominantly manifested as corneal disorders or ocular neuromuscular disorders. The median onset of ocular toxicity varied considerably, with enfortumab vedotin showing the earliest median onset at 12.5 days. Conclusions: Our study demonstrates the association between ADCs and ocular AEs based on real-world data, providing valuable guidance for clinicians when prescribing ADCs. And we found some important safety signals that have not been mentioned in the label or previous studies. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV)-based vectors are the most frequently used platform for retinal gene therapy. Initially explored for the treatment of loss-of-function mutations underpinning many inherited retinal diseases, AAV-based ocular gene therapies are increasingly used to transduce endogenous cells to produce therapeutic proteins, thus producing site-specific biofactories. Relatively invasive ocular routes of administration (ROA) mean prominent procedure-related in-life, and histopathological findings may be observed with some regularity. Test article-related findings may vary with the ROA and cell populations transduced, with retinal pigmented epithelium (RPE) changes prominent (ranging from pigment alteration through degeneration, with or without associated degeneration of the overlying retina) with subretinal ROA, and more anterior changes (iris, ciliary body) generally observed with the intravitreal ROA. Ocular inflammation is the most frequent finding that occurs nonclinically and in patients, and is particularly pronounced with intravitreal administration. Extraocular findings may be observed in extraocular muscles, regional ganglia, or central visual pathways with multiple ocular ROA. Work is still needed to understand the mechanisms underpinning many of these ocular and extraocular findings. Emerging patient data is helping to clarify both the potential for translating nonclinical findings to predict possible human responses and the applicability of nonclinical biomonitoring methods to the clinical setting. [ABSTRACT FROM AUTHOR]

MEDI2228 is an antibody drug conjugate (ADC) comprised of a fully human B-cell maturation antigen (BCMA) antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer. This phase 1 trial evaluated MEDI2228 in patients with relapsed/refractory (R/R) multiple myeloma (MM), who received prior treatment with approved agents from 3 classes of antimyeloma drugs (proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies). Primary endpoint was safety and tolerability; secondary endpoints included efficacy, pharmacokinetics, and immunogenicity. A total of 107 patients were treated and the maximum tolerated dose (MTD) was 0.14 mg/kg Q3W. Two patients had dose-limiting toxicities (DLTs; thrombocytopenia; 0.20 mg/kg Q3W). The most frequent treatment-related adverse events were photophobia (43.9%), rash (29.0%), and thrombocytopenia (19.6%). In MTD cohort A (n = 41), the objective response rate (ORR) was 56.1%, with 1 stringent complete response, 9 very good partial responses, and 13 partial responses. ORR was 53.3% in triple refractory patients. In cohort B (n=25), ORR was 32%. Although MEDI2228 demonstrated efficacy in R/R MM, ocular toxicity precluded further development of this drug. KEY POINTS: MEDI2228 is an ADC comprised of a fully human anti-BCMA antibody conjugated to the cytotoxic PBD payload, tesirine. MEDI2228 monotherapy demonstrated efficacy across all dose levels; and responses were observed in patients with triple refractory MM. This study further validates BCMA as a target for ADC-based therapy in MM; ocular toxicity precluded further clinical development. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are an emerging field of cancer treatments that are becoming more widespread in their use. However, there are potential ocular toxicities associated with these drugs that ophthalmologists need to be aware of to better maintain ocular health as patients undergo rigorous medical treatment for their conditions. While many ADCs have been approved by the Food and Drug Administration (FDA), many subsequent reports have been published regarding additional ocular side effects these drugs may cause. This review provides ophthalmologists with a practical guide on how to treat ocular toxicities associated with all FDA-approved ADCs to date. The potential pathophysiology of side effects is also discussed. [ABSTRACT FROM AUTHOR]

Objective: The widespread use of nanoparticles in recent years has increased the risk of ocular exposure. zinc oxide (ZnO) is widely used in the field of cosmetics because of its unique chemical properties. The application of graphene oxide (GO) as an emerging nanomaterial in the field of eye drops is also gradually emerging. Currently, research on ZnO and GO eye exposure mainly focuses on application or toxicity to optic nerve cells. There's less study on corneal wound healing effects. and the previous research hasn't compared ZnO and GO corneal toxicity. Methods: We systematically established a complete chain study of in vitro and in vivo experiments and mouse corneal injury model, and comprehensively evaluated the ocular safety and toxicity of ZnO and GO. Results: We found that 50 ug/mL GO and 0.5 ug/mL ZnO can reduce human corneal epithelial cells (HCEpiC) viability in a concentration-dependent manner. Short-term repeated exposure to ZnO can cause sterile inflammation of the cornea with concentration-dependence, while GO have not been significantly altered. 50 ug/mL ZnO could significantly delay the healing of corneal wounds, while GO did not change wound healing. Conclusion: The toxic effect of ZnO is higher than that of GO. Inflammatory signal transduction, oxidative stress and apopnano zitosis are involved in the ocular toxicity injury process of nanoparticles. Research can provide a judgement basis for people's eye health and eye protection risk control. [ABSTRACT FROM AUTHOR]

Anti‐vascular endothelial growth factor (VEGF) drugs suppress choroidal neovascularisation (CNV), thus improving vision. However, some patients may have a poor response or develop resistance to anti‐VEGF drugs. Geraniin (GE), a polyphenol isolated from an herb called Phyllanthus amarus, possesses anti‐angiogenic properties. This study aimed to explore the mechanism of action of GE in CNV. GE was found to activate the angiotensin‐converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang‐[1–7])/MAS1 proto‐oncogene, G protein‐coupled receptor (MasR)/interleukin‐10 (IL‐10) pathway in hypoxic human choroidal endothelial cells (HCECs) in vitro and mouse models of laser‐induced CNV in vivo. Activation of the ACE2/Ang‐(1–7)/MasR/IL‐10 pathway by GE attenuated the proliferative, migratory, and tube‐forming abilities of hypoxic HCECs and prevented the development of CNV in mice. Notably, GE did not cause ocular or systemic toxicity in mice with CNV. These findings suggest that GE alleviates CNV by activating the ACE2/Ang‐(1–7)/MasR/IL‐10 pathway in choroidal endothelial cells (CECs). [ABSTRACT FROM AUTHOR]

Eye examination plays an important role when living individuals are forensically investigated. The iris colour, retinal scans and other biometric features may be used for identification purposes while visual impairments may have legal implications in employment, driving and accidents. Ocular manifestations provide clues regarding substance abuse, poisoning and toxicity, and evidence of trauma, abuse or disease can be revealed along with psychological traits and lifestyle. Thus, the eye is a valuable tool in forensic investigations of living subjects, providing identifying characteristics along with health information. This review focuses on the medico-legal aspects of the eye's contribution when the living are subjected to forensic examination. [ABSTRACT FROM AUTHOR]

Considering the limited information on the impact of PM2.5 content on ocular health, a follow-up study was conducted on 50 healthy adults. Samples were collected twice, once before the PM2.5 exposure season and again after exposure. Daily PM2.5 concentration data was gathered from Thung Satok monitoring station. All subjects completed the self-structured ocular symptom questionnaire. The concentrations of 1-OHP were determined using HPLC-FLD. Logistic regression analysis investigated the relationship between PM2.5 toxicity and ocular symptoms. The findings revealed that daily PM2.5 concentrations surpassed the WHO-recommended range by around threefold. Exposure to PM2.5 significantly raised the likelihood of ocular redness (adjusted OR: 12.39, 95% CI), watering (adjusted OR: 2.56, 95% CI), and dryness (adjusted OR: 5.06, 95% CI). Additionally, these symptoms had an exposure-response relationship with increasing 1-OHP levels. Ocular symptoms worsened in frequency and severity during the high PM2.5 season, showing a strong link to elevated PM2.5 levels. Lymphocyte counts were also positively correlated with redness, watering, and dryness during high PM2.5 exposure. In conclusion, our study shows that subjects exposed to higher PM2.5 levels presented more significant ocular surface alterations. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) are a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy agents. ADCs have been available for over a decade, but in gynecological cancers, these agents are relatively new with great promise ahead. More than 80% of ongoing trials in gynecological cancers are evaluating ADCs' safety and efficacy, of which 40% are early-phase trials. Around twenty ADCs are currently under investigation, either alone or in combination with chemotherapies or immune checkpoint inhibitors. Among them, mirvetuximab soravtansine has been recently approved by the Food and Drug Administration (FDA) in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent or in combination. Tisotumab vedotin and trastuzumab deruxtecan are also now approved by the FDA in patients with pre-treated cervical and uterine cancers and further investigation is ongoing. Overall, the toxicity profiles of ADCs are acceptable. Ocular toxicity is one of the specific side effects of some ADCs, but most of the cases are manageable with the use of prophylactic steroids and dose adjustments. This review aims to provide an overview of the fundamental and operational features of ADCs and examine the latest and most promising data, with a particular focus on the Canadian viewpoint. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering significant improvements in patient survival across various malignancies. However, their use is associated with a broad spectrum of immune-related adverse events (irAEs), including those affecting the eye and its surrounding structures, collectively termed ocular irAEs (OirAEs). Although rare, OirAEs (e.g., keratitis, uveitis, retinal vasculitis, etc.) can significantly impact a patient's quality of life, leading to ocular complications if left untreated. This review provides a comprehensive overview of OirAEs associated with ICIs, including their clinical manifestations, underlying mechanisms, and current management strategies. We delve into the anterior and posterior segment adverse events, highlighting conditions such as dry eye, uveitis, and retinal disorders, as well as neuro-ophthalmic and orbital complications. Furthermore, we discuss the challenges in diagnosing and treating these conditions, particularly given the overlap with other autoimmune and paraneoplastic syndromes. Finally, we identify key knowledge gaps and suggest future research directions aimed at optimizing the management of OirAEs while maintaining the efficacy of cancer therapy. This review underscores the need for increased awareness among clinicians to prevent irreversible ocular damage and enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Various techniques using fluorescent reporter probes have been developed, such as GFP transgenic mouse lines that are used to detect spatial–temporal expression levels of genes. Although GFP expression is largely considered non-toxic, recent reports have indicated that under certain conditions GFP can display cellular toxicity. We hereby report the nuclear toxicity of H2B-GFP using a K14 specific Tet-on reporter mouse system. Using this system, GFP accumulates in the nucleus of all K14 expressing cells, such as the ocular surface epithelia and ocular adnexa. Expression of high levels of nuclear GFP during embryonic stages led to an eye open-at-birth (EOB) phenotype and abnormal ocular adnexa development and during adult and aging stages showed notable toxicity to ocular tissues. Other tissues, such as skin, also presented multiple defects associated with H2B-GFP expression. This toxicity was found to be concentration dependent, with homozygous mice presenting extremely high toxicity, while heterozygous mice presented limited toxicity. Upon induction, the accumulation of H2B-GFP in the nucleus of homozygous mice led to apoptosis within 2 weeks. This study therefore shows that although the use of nuclear GFP reporter mice is a valuable tool, at high levels, nuclear GFP can be toxic, leading to cell death and affecting tissue function. [ABSTRACT FROM AUTHOR]

Cancer continues to pose a substantial global health burden and remains one of the leading causes of mortality worldwide. Encouragingly, survival rates have consistently improved, largely due to advancements in diagnosis and treatment. The development of anticancer drugs, including cytotoxic chemotherapy, hormonal agents, and targeted therapies, has significantly enhanced the efficacy of cancer treatments. Chemotherapy-induced ocular toxicity encompasses a wide range of disorders, influenced by the eye's unique anatomical and physiological characteristics. The mechanisms of these drugs can lead to systemic and ocular side effects, including cytotoxicity, inflammation, and neurotoxicity. While ocular side effects from targeted therapies are less common, they can be severe, disabling, and potentially irreversible. In some cases, immediate discontinuation of the drug may be necessary to prevent vision-threatening complications. Understanding these ocular side effects is crucial for early recognition and intervention by ophthalmologists and oncologists to prevent blindness. Additionally, anticipating treatment-related toxicities enables pharmacists to develop strategies that minimize or mitigate these side effects. This review focuses on the ocular toxicity associated with the most significant anticancer chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is an autoimmune disorder requiring long-term combination therapy with diseasemodifying antirheumatic drugs (DMARDs), non-steroidal anti-inflammatory agents (NSAIDS), low-dose steroids, proton pump inhibitors, calcium, and folic acid and these drugs cause multitude of side effects. This study on the efficacy and tolerability of drugs used in RA among South Indian patients can guide in tailoring a treatment regimen more suited for South Indian population. Aims and Objectives: The main objective of this study was to evaluate the efficacy and tolerability of drugs used in the treatment of RA among South Indian patients. Materials and Methods: In this prospective observational study, 120 newly diagnosed RA patients attending rheumatology outpatient department in a tertiary care center in South India were recruited after obtaining Institutional Ethics Committee approval and informed consent. Sociodemographic details and baseline investigations were done. Each patient was followed up for a period of 6 months wherein, response to treatment was evaluated and adverse drug reactions (ADRs) reported were collected, analyzed and appropriate treatment was instituted. Data analysis was done using SPSS software. Results: One hundred patients completed the study. There was female preponderance (85%) and 38% were rheumatoid factor positive. Efficacy of combination therapy was evidenced falling erythrocyte sedimentation rate (P < 0.001), modified health assessment questionnaire,and disease activity score 28 scorings after 1st, 3rd, and 6th month of therapy (P < 0.001) and improvement in hemoglobin count (P < 0.001). The number of swollen joints was also significantly reduced (P < 0.001). Common ADRs reported were gastritis (29%), mucosal ulcers (10%), macrocytic anemia (3%), chloroquine-related ocular toxicity (2%). Conclusion: NSAIDS and steroids helped to achieve early remission and caused most of adverse effects. Methotrexate and chloroquine had good tolerability and were preferred DMARDs in our center. Thus, we conclude that the combination therapy used in our center is efficacious and well tolerated by South Indian population. [ABSTRACT FROM AUTHOR]

Background: Ocular toxicity is a severe adverse effect that limits the chronic clinical use of the antiarrhythmic drug amiodarone. Here, we aimed to evaluate the cytoprotective effect of artemisinin and explore the potential signalling pathways in human retinal pigment epithelial (RPE) cell cultures. Methods: D407 cell cultures were exposed to amiodarone and the impact of artemisinin was evaluated. The key parameters included lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) generation, and the mitochondrial membrane potential (MMP). We also assessed the protein levels of cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), phosphorylated adenosine monophosphate-activated protein kinase (AMPK)ɑ (p-AMPK), calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), and nuclear factor erythroid 2-related factor 2 (Nrf2). Results: Artemisinin reduced the cytotoxicity induced by amiodarone, as reflected by decreased LDH release, ROS generation, and MMP disruption. Additionally, artemisinin increased p-AMPK, CaMKK2, and Nrf2 protein levels. Inhibition of AMPK, CaMKK2, or Nrf2 abolished the cytoprotective effect of artemisinin. AMPK activation and Nrf2 knockdown further supported its protective role. Conclusions: Artemisinin protected RPE cells from amiodarone-induced damage via the CaMKK2/AMPK/Nrf2 pathway. The in vivo experiments in mice confirmed its efficacy in preventing retinal injury caused by amiodarone. These results suggest that an artemisinin-based eye formulation could be repurposed for treating amiodarone-induced ocular toxicity. [ABSTRACT FROM AUTHOR]

Ocular damage in systemic lupus erythematosus (SLE) may cause insidious visual impairment, but its clinical features and the risk of hydroxychloroquine (HCQ)-related complications are still controversial. We performed a meta-analysis to evaluate ocular damage in SLE, the correlation between eye and systemic involvement, and the ocular side effects of treatment. The database PubMed, Embase, and Ovid were used for literature from reception to July, 2023, and the calculation was carried out with R. About 48,693 patients from 66 studies were included. The results indicated that ocular damage in SLE was insidious, appearing in 28 % of patients with no complaints. The most common symptoms and manifestations were dry eye (30 %) and keratoconjunctivitis sicca (26 %). Retinopathy was detected in 10 % of patients and was related to antiphospholipid antibodies (25 % versus 8 %). The proportion of retinopathy also significantly increased in patients with lupus nephropathy or neuropsychiatric systemic lupus erythematosus (risk ratio of 2.29 and 1.95, respectively). HCQ was used in 82 % of patients, of which 4 % suffered from ocular toxicity. HCQ-related retinopathy was dose-dependent. Dosage below 5 mg/kg/d was relatively effective and safe for long-term use, while routine examination was recommended. • Ocular damage in SLE. • Retinopathy is related with APL, as well as renal and CNS involvement. • HCQ-related retinopathy in SLE is dose-dependent. [ABSTRACT FROM AUTHOR]

As the cosmetic market continues to transform, innovative ingredients such as biosurfactants (BS) emerge as a fundamental step towards a generation of cosmetic products characterized by efficacy, safety, and environmental responsibility. In alignment with the global push towards natural, renewable, and non‐toxic materials, BS stands out as an interesting alternative to conventional synthetic surfactants. BS are a type of green surfactants and compared to synthetic surfactants derived from petroleum they are more biodegradable and have low or no toxicity. This work aimed to investigate the suitability of a biosurfactant extracted from the yeast Scheffersomyces shehatae (BS‐SS) to be used in cosmetic applications. The cytotoxicity of the BS‐SS was tested in fibroblast (L929) and keratinocyte (HaCaT) cell lines and the potential for ocular irritation was assessed by the hen's egg chorioallantoic membrane test (HET‐CAM). The cleaning efficiency of the BS‐SS was measured as the ability of make‐up removal in pig skin. Our results showed that the IC 50 values were 10.49 mg/mL for fibroblasts and 11.77 mg/mL for keratinocytes, and the biosurfactant did not result in hemorrhage, lysis, and coagulation damages in the chorioallantoic membrane, which classifies the biosurfactant solution as non‐irritant. Therefore, ocular toxicity and in vitro skin cell toxicity results showed that BS‐SS can be tolerable and safe for cosmetic purposes. BS‐SS featured promising cleaning properties, similar to the cleansing activity of the 1% SDS solution and of micellar water for lipstick and foundation products. In conclusion, the results indicate its potential use in cosmetic applications. [ABSTRACT FROM AUTHOR]

Purpose: Antibody-drug conjugates (ADCs) are a relatively recent advance in the delivery of chemotherapeutics that improve targeting of cytotoxic agents. However, despite their antitumor activity, severe ocular adverse effects, including vision loss, have been reported for several ADCs. The nonspecific uptake of ADCs into human corneal epithelial cells (HCECs) and their precursors via macropinocytosis has been proposed to be the primary mechanism of ocular toxicity. In this study, we evaluated the ability of a novel polymer, poly(l-lysine)–graft–poly(ethylene glycol) (PLL-g-PEG), to decrease the ADC rituximab-mc monomethylauristatin F (MMAF) (RIX) uptake into human corneal epithelial (HCE-T) cells. Methods: HCE-T cells were exposed to increasing concentrations of RIX to determine inhibition of cell proliferation. HCE-T cells were treated with PLL-g-PEG, the macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA), or vehicle. After 30 min of incubation, RIX was added. ADC was detected by fluorescent anti-human immunoglobulin G and fluorescently conjugated dextran as viewed by microscopy. Results: RIX caused dose-dependent inhibition of HCE-T cell proliferation. EIPA significantly reduced RIX uptake and decreased macropinocytosis as assessed by direct quantification of RIX using a fluorescently conjugated anti-human antibody as well as quantification of macropinocytosis using fluorescently conjugated dextran. PLL-g-PEG resulted in a dose-dependent inhibition of RIX uptake with half-maximal inhibitory concentrations of 0.022%–0.023% PLL-g-PEG. Conclusion: The data show PLL-g-PEG to be a potent inhibitor of RIX uptake by corneal epithelial cells and support its use as a novel therapeutic approach for the prevention of ocular adverse events associated with ADC therapy. [ABSTRACT FROM AUTHOR]

The treatment landscape of gynecologic cancers has expanded in recent years to include targeted and immune-based therapies. These therapies often have ocular side effects not seen with conventional chemotherapies, some of which can cause significant visual impairment if not recognized in a timely fashion. Clinicians must know how to appropriately identify, mitigate, and treat these ocular adverse events. Management often involves working with an interdisciplinary team of eye specialists, and it is important to know when to refer patients for specialized care. Proactive identification of eye specialists, especially in rural and community settings where access to care can be limited, may be necessary. Here, we discuss the management of common ocular toxicities seen with novel anticancer agents used to treat gynecologic cancers. • Novel targeted and immunological agents may cause ocular toxicity. • Eye examination and mitigation strategies are required for some of these agents. • Prompt recognition and appropriate management of ocular adverse events are imperative. [ABSTRACT FROM AUTHOR]

Eye plaque brachytherapy (EPBT) is the most common treatment for uveal melanoma with high local control rates of 95–100%. When local recurrences occur following EPBT, salvage options include enucleation, transpupillary thermotherapy (TTT), external beam radiation, or re-irradiation with EPBT. The purpose of this study is to report our institution's experience with EPBT re-irradiation for locally recurrent uveal melanoma. Patients were included if they were previously treated for uveal melanoma with EPBT, experienced local recurrence, and were subsequently treated at our institution with EPBT from 2016– 2020. A total of 5 patients with median age 68 years were included. All patients were initially treated at an outside institution (OSI) with Iodine-125 or Ruthenium-106 EPBT. Mean time between EPBT at the OSI and EPBT at our facility was 130 months (range 28–231 months). Patients were re-irradiated with Iodine-125 EPBT prescribed to 85 Gy over 168 hours. Median follow up after re-treatment at our center was 24 months. Local control among this cohort was 100%. Metastasis occurred in two patients after re-treatment, at 8 months and 7 months. At last follow up, all treated lesions were decreased in size. Four patients experienced worsening visual acuity. Four patients developed cataracts, while two patients developed radiation retinopathy with cystoid macular edema requiring anti-VEGF injections. One patient developed radiation retinopathy but did not require injections. No patients required enucleation. Re-treatment of locally recurrent uveal melanomas with EPBT is a feasible alternative to enucleation with a high local control rate. Ocular toxicities have not been significant enough to require enucleation. [ABSTRACT FROM AUTHOR]

Background: Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database. Methods: Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated. Results: A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26–1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2–24.58)], dry eye [ROR = 9.69, 95% CI (8.81–10.66)], night blindness [ROR = 259.87, 95% CI (228.23–295.89)], vision blurred [ROR = 1.78, 95% CI (1.57–2.02)], photophobia [ROR = 10.45, 95% CI (9.07–12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88–27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3–178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66–156.69)], eye disorder [ROR = 2.71, 95% CI (2.21–3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days. Conclusion: ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and tolerability of pooled human immune globulins, Flebogamma® 5% DIF and Flebogamma® 10% DIF, administered by topical ophthalmic instillation to New Zealand White (NZW) rabbits. Methods: Male NZW rabbits were used in this study. In the acute single dose tolerability study, rabbits (n = 12) received a single topical dose of Flebogamma® 5% DIF. In the two-week repeated-dose tolerability study, rabbits (n = 5 for each group) were administered either Flebogamma® 5% DIF or Flebogamma® 10% DIF by topical bilateral administration four times daily (q.i.d.) between 8 am and 6 pm for a period of two weeks. Full ophthalmic examinations were conducted to evaluate ocular tolerability at baseline, Day 7, and Day 14. Results: In the acute single dose study, mild hyperaemia was observed in 1 out of 4 eyes at each 4 h and 24 h post-instillation of Flebogamma® 5% DIF. In the repeated dose study, no ocular signs were detected after q.i.d. topical instillation of Flebogamma® 5% DIF, while Flebogamma® 10% DIF resulted in mild hyperaemia in 8 out of 10 eyes on Day 7, and 5 out of 10 eyes on Day 14. No positive corneal fluorescein staining was detected. Schirmer tear test results were unremarkable. No other ocular signs were observed. Administration of immune globulins had no effect on intraocular pressure. Conclusions: Flebogamma® 5% DIF and Flebogamma® 10% DIF were well-tolerated by NZW rabbits following single and repeat dose topical ophthalmic administration, supporting the future development of topical pooled human immune globulins for the treatment of ocular surface disease. [ABSTRACT FROM AUTHOR]

Objective: Miltefosine stands as the sole oral medication approved for the treatment of leishmaniasis. The appearance of severe ophthalmic toxicities induced by miltefosine in the context of leishmaniasis treatment is a matter of significant concern. The main objective of this study is to present a comprehensive summary of the ophthalmic adverse effects associated with miltefosine when used in the treatment of leishmaniasis. Methods: A systematic search was performed on PubMed, ScienceDirect, Embase, Scopus, and Google Scholar, covering articles from inception up to June 2023, without language restrictions, to identify relevant studies documenting ocular toxicity following miltefosine treatment for leishmaniasis. Results: A total of eight studies involving 31 leishmaniasis patients who developed ocular toxicities while undergoing miltefosine treatment were included in the analysis. These studies were conducted in various regions, with five originating from India, two from Bangladesh, and one from Nepal. Patients presented a spectrum of ophthalmic complications, including uveitis, keratitis, scleritis, and Mooren's ulcer. Commonly reported symptoms included pain, redness, excessive tearing, partial vision impairment, permanent blindness, light sensitivity, and the appearance of white spots on the eye. On average, patients received miltefosine treatment for a duration of 47 days before experiencing the onset of ocular problems. It is important to note that the risk of ocular toxicities increases with prolonged use of miltefosine. Conclusions: Therefore, to mitigate the potential for irreversible damage to the eyes, it is imperative that all individuals undergoing miltefosine therapy undergo regular eye examinations. [ABSTRACT FROM AUTHOR]

Aims: Vigabatrin is an antiepileptic drug used to treat some forms of severe epilepsy in children. The main adverse effect is ocular toxicity, which is related to the cumulative dose. The aim of the study is to identify an acceptable exposure range, both through the development of a population pharmacokinetic model of vigabatrin in children enabling us to calculate patient exposure and through the study of therapeutic response. Methods: We performed a retrospective study including children with epilepsy followed at Necker‐Enfants Malades hospital who had a vigabatrin assay between January 2019 and January 2022. The population pharmacokinetic study was performed on Monolix2021 using a nonlinear mixed‐effects modelling approach. Children treated for epileptic spasms were classified into responder and nonresponder groups according to whether the spasms resolved, in order to identify an effective plasma exposure range. Results: We included 79 patients and analysed 159 samples. The median age was 4.2 years (range 0.3–18). A 2‐compartment model with allometry and creatinine clearance on clearance best fit our data. Exposure analysis was performed on 61 patients with epileptic spasms. Of the 22 patients who responded (36%), 95% had an AUC0–24 between 264 and 549 mg.h.L−1. Conclusions: The population pharmacokinetic model allowed us to identify bodyweight and creatinine clearance as the 2 main factors explaining the observed interindividual variability of vigabatrin. An acceptable exposure range was defined in this study. A target concentration intervention approach using this pharmacokinetic model could be used to avoid overexposure in responder patients. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to describe a case of bilateral keratoconjunctivitis after exposure to the toxic sap of Euphorbia lathyris. Case Report: A 76-year-old gentleman presented after exposure to E. lathyris whilst he was gardening. He had 6/12 visual acuity in his right eye, and 6/4 in his left. Examination revealed marked periocular dermatitis, conjunctival injection and corneal oedema in the right eye with diffuse punctate epithelial staining. He was treated with ocular irrigation, topical steroids, antibiotics, cycloplegics and lubricants. Over 48 h, his left eye started to become symptomatic. He developed bilateral corneal epithelial defects and anterior chamber inflammation. His visual acuity worsened to 6/36 right and 6/24 left. At his 3-week follow-up, there was marked improvement in the resolution of the toxic keratoconjunctivitis in both eyes. Conclusion: Toxic sap from E. lathyris can cause severe keratoconjunctivitis. Irrigation of both eyes despite unilateral symptoms and early follow-up should be considered signs of toxicity may only become evident after 24–48 h. [ABSTRACT FROM AUTHOR]

Systemic use of Ivermectin has been reported to incite blindness in humans and veterinary patients. This study was designed to investigate the systemic and intravitreal effect of Ivermectin on ocular and retinal health and its attenuation with topical Dexamethasone. Systemic injection of Ivermectin@ 1.6 mg/kg S/C was administered, thrice a week for three weeks to New Zealand White rabbits (N = 4) with and without topical drops of Verapamil (N = 4). Pre and post-treatment ocular examination was conducted. At the end of three weeks the eyes were collected for histopathology. 0.2 ml of Ivermectin solution (1.6 mg/ml) was injected intravitreally in one eye of the rabbit (N = 8), Half the rabbits received 0.1% dexamethasone drops thrice daily for 7 days, while the controls received PBS. Pre and post-treatment, detailed examination was conducted, which included the Schirmer Tear test, Fluorescein staining, Intraocular pressure, slit lamp biomicroscopy and fundus photography. The retina was harvested for histopathological and tunnel assay. Systemic therapy with Ivermectin, with and without Verapamil did not incite any adverse response in the eye. Intravitreal Ivermectin evoked severe uveitis 4/4, cataract 3/4, corneal erosion 3/4 eyes and severe inflammatory response. Eyes that received dexamethasone were rescued from the adverse changes as demonstrated clinically, by histopathology and prevention of apoptosis. Intravitreal Ivermectin incites severe inflammatory response. Topical dexamethasone counters the ocular toxicity incited by Ivermectin. [ABSTRACT FROM AUTHOR]

Although the therapeutic landscape for multiple myeloma (MM) has expanded, the disease always tends to relapse. In an attempt to obtain deep and durable responses, each relapse requires the use of a new strategy. In recent years, new treatment options have emerged, even for heavily treated patients. Novel, well-tolerated, and highly effective therapies in the relapsed/refractory (RRMM) setting currently represent a real hope. Belantamab mafodotin (BLENREP™) is a first-in-class monoclonal antibody-drug conjugate whose target is B-cell maturation antigen conjugated to the cytotoxic microtubule inhibitor monomethyl auristatin F. Here, we present two cases of heavily pre-treated RRMM patients that were favorably treated with belantamab mafodotin, obtaining at least a partial response. Treatment was well tolerated and is ongoing. This is a rare report on real life clinical use of belantamab mafodotin outside of controlled clinical trials and provides information on efficacy and safety of this anti-myeloma new class of drugs. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) is a chemotherapeutic agent employed as a therapy for different solid tumors. CP elicits many negative side effects including ocular toxicity. L-arginine able to increase the anti-inflammatory cytokine levels in the bloodstream. This study aimed to evaluate the possible protective impact of L-arginine against ocular toxicity of cisplatin through its anti-inflammatory action. Forty male rats were utilized in this experiment. The treatment protocol duration lasted for one week. The rats were divided randomly into four equal groups, as follows: the normal control group (G1) received a single intraperitoneal injection of normal saline, Cisplatin-administered group (G2) received single intraperitoneal injection of cisplatin in a dose (10 mg/kg body weight), Cisplatin + L-arginine-treated group (G3) received i.p. injection of cisplatin in a dose (10 mg/kg b.wt.) followed immediately by i.p. injection of L-arginine in a dose (10 mg/kg b.wt.), and L-arginine-treated group (G4) received intraperitoneal injection of 10 mg/kg b.wt. L-arginine. The protective effect of L-arginine was assessed through histopathology and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) in ocular tissues. Cisplatin-administered group revealed corneal neovascularization, stromal inflammatory infiltration, corneal epithelial hyperplasia, and endothelial degeneration. Sclera revealed vascular congestion and inflammatory infiltrates. There were congested blood vessels, apoptosis, and a decrease the ganglionic cells number in the retinal tissue. Ciliary body had epithelial necrosis, congestion, and hemorrhage. These pathological changes were attenuated to be mild in the cisplatin + L-arginine-treated group. The intensity of the immunohistochemical expression of iNOS appeared weak and significantly decreased in G3 compared to G2. The obtained data validate that Co-treatment of cisplatin with L-arginine cause a reduction in histopathological ocular damage through its anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

The accurate identification of chemicals with ocular toxicity is of paramount importance in health hazard assessment. In contemporary chemical toxicology, there is a growing emphasis on refining, reducing, and replacing animal testing in safety evaluations. Therefore, the development of robust computational tools is crucial for regulatory applications. The performance of predictive models is heavily reliant on the quality and quantity of data. In this investigation, we amalgamated the most extensive dataset (4901 compounds) sourced from governmental GHS‐compliant databases and literature to develop binary classification models of chemical ocular toxicity. We employed 12 molecular representations in conjunction with six machine learning algorithms and two deep learning algorithms to create a series of binary classification models. The findings indicated that the deep learning method GCN outperformed the machine learning models in cross‐validation, achieving an impressive AUC of 0.915. However, the top‐performing machine learning model (RF‐Descriptor) demonstrated excellent performance with an AUC of 0.869 on the test set and was therefore selected as the best model. To enhance model interpretability, we conducted the SHAP method and attention weights analysis. The two approaches offered visual depictions of the relevance of key descriptors and substructures in predicting ocular toxicity of chemicals. Thus, we successfully struck a delicate balance between data quality and model interpretability, rendering our model valuable for predicting and comprehending potential ocular‐toxic compounds in the early stages of drug discovery. Effective identification of chemicals causing ocular toxicity is critical to health hazard assessment. In this study, we carefully integrated the largest dataset (4,901 compounds) from official GHS‐compliant databases and literature. Machine learning and deep learning classification prediction models were constructed, among which the RF‐Descriptor model performed the best. Furthermore, we used the SHAP method and attention weights analysis to enhance the model's interpretability, making it valuable in predicting and understanding potential ocular‐toxic compounds in the early stages of drug discovery. [ABSTRACT FROM AUTHOR]

Purpose: Favipiravir (FAV) used against COVID-19 is an antiviral drug that causes adverse reactions, such as hyperuricaemia, liver damage, and hematopoetic toxicity. The aim of the study was to investigate the systemic and ocular side-effects of FAV in rats, for the first time.Materials and methods: A total of 18 albino male Wistar rats were used in the study. The rats were divided into 3 groups as the healthy group (HG), the group given 50 mg/kg/day favipiravir (FAV50), and the group given 200 mg/kg/d favipiravir (FAV200). These doses were given to the experimental groups for one week. At the end of the experiment histopathological examinations were performed on the conjunctiva and sclera of the eye. In addition, malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were measured in blood samples taken from rats. Results: Compared to HG, the MDA (1.37 ± 0.61 vs. 4.82 ± 1.40 µmol/mL), IL-1β (2.52 ± 1.14 vs. 6.67 ± 1.99 pg/mL), and TNF-α levels (3.28 ± 1.42 vs. 8.53 ± 3.06 pg/mL) of the FAV200 group were higher. The levels of tGSH (7.58 ± 1.98 vs. 2.50 ± 0.98 nmol/mL) and SOD (13.63 ± 3.43 vs. 3.81 ± 1.43 U/mL) the FAV200 group were lower than the HG (p < 0.05, for all). The degree of damage to the cornea and sclera of the FAV200 group was quite high according to HG (p < 0.001). Conclusions: FAV can cause damage to rat conjunctiva and sclera by increasing oxidant stress and inflammation at high dose. [ABSTRACT FROM AUTHOR]

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity. [ABSTRACT FROM AUTHOR]

Ocular tissue, especially the cornea, is overly sensitive to chemical exposures. The availability and adoption of chemical threat agent chloropicrin (CP) is growing in the United States as a pesticide and fumigant; thereby increasing the risk of its use in warfare, terrorist attacks and non-intentional exposure. Exposure to CP results in immediate ocular, respiratory, and dermal injury; however, we lack knowledge on its mechanism of toxicity as well as of its breakdown products like chlorine and phosgene, and effective therapies are elusive. Herein, we have reviewed the recent findings on exposure route, toxicity and likely mechanisms of CP induced ocular toxicity based on other vesicating chemical warfare agents that cause ocular injury. We have focused on the implication of their toxicity and mechanistic outcomes in the ocular tissue, especially the cornea, which could be useful in the development of broad-spectrum effective therapeutic options. We have discussed on the potential countermeasures, overall hallmarks and challenges involved in studying ocular injuries from chemical threat agent exposures. Finally, we reviewed useful available technologies and methods that can assist in the identification of effective medical countermeasures for chemical threat agents related ocular injuries. [Display omitted] • Chloropicrin, a warfare agent, is used as a pesticide and fumigating agent. • Chloropicrin is a choking chemical threat agent that caused severe ocular injury. • The mechanism of ocular injury from chloropicrin exposure is unknown. • There is currently no available targeted treatment for chloropicrin induced injuries. [ABSTRACT FROM AUTHOR]

Background: Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. Purpose: This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. Methods: The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. Results: While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. Conclusion: This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice. [ABSTRACT FROM AUTHOR]

Background: Ocular Toxicity is one of the most common complication of Ethambutol. It can be in the form of both reversible and irreversible blindness. Aim and Objective: To study Ethambutol induced ocular toxicity in patients using anti tuberculosis treatment (ATT). To characterize duration of treatment at which ocular symptoms are starting. To evaluate the dose of ethambutol at which ocular toxicity is evident. To study the reversibility of ocular toxicity in the form of improvement in visual acuity after stopping ethambutol. Methodology: Patients on ATT referred to ASRAM Respiratory Medicine department from various ophthalmology hospitals for blurring of vision due to Ethambutol were taken into study from April 2022-2023 after taking consent. Results: Most of the patient's symptoms that is blurring of vision started after 3-4 months of ATT [40.15%] and mean dosage is 20.86 mg/kg/day. Conclusion: In most patients Ethambutol induced ocular toxicity is observed in continuation phase of treatment and those who are falling at lower end of body-weight band. In few patients with stopping of Ethambutol blurring of vision was reversible. [ABSTRACT FROM AUTHOR]

Anti‐human epidermal growth factor receptor 2 (HER2) agents have exhibited pronounced tumor‐inhibitory activity, yet the accompanying ocular toxicity has frequently been underestimated. We aim to conduct a comprehensive comparative analysis of ocular toxicity risk related to various anti‐HER2 agents. We executed a retrospective pharmacovigilance investigation based on the FDA Adverse Event Reporting System (FAERS) database, covering the period from Q2 2018 to Q1 2023. The disproportionality analysis was performed to assess ocular toxicity risk. Multivariate logistic regression was implemented to mitigate potential biases. Moreover, the time to onset of ocular toxicity was also evaluated. A total of 3467 ocular adverse event (AE) reports concerning anti‐HER2 agents were collected. At the preferred term (PT) level, there were 69 positive signals, among which excessive eye blinking, abnormal sensation in the eye, and asthenopia presented a significant risk. In comparison to tyrosine kinase inhibitors (TKIs), antibody drugs were associated with a broader range of ocular disorders at Standardized MedDRA Queries (SMQ)levels, including conjunctival disorders, corneal disorders, ocular infections, ocular motility disorders, optic nerve disorders, and retinal disorders. In terms of onset time, pertuzumab displayed an earlier onset at 21.5 days, while trastuzumab deruxtecan had the latest at 91.5 days. In summary, our study reveals varying degrees of ocular toxicity related to anti‐HER2 agents, with a significantly higher risk observed in antibody drugs. Additionally, novel ocular toxicity signals, not documented in product labels, have been detected. In the future, further research will be necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is one of the most commonly used organophosphosphatebased (OP) insecticides. Its wide use has led to higher morbidity and mortality, especially in developing countries. Moringa seed extracts (MSE) have shown neuroprotective activity, antioxidant, anti-inflammatory, and antibacterial features. The literature lacks data investigating the role of MSE against CPFinduced cerebral and ocular toxicity in mice. Therefore, we aim to investigate this concern. A total of 40 mature male Wistar Albino mice were randomly distributed to five groups. Initially, they underwent a one-week adaptation period, followed by a one-week treatment regimen. The groups included a control group that received saline, MSE 100 mg/kg, CPF 12 mg/kg, CPF-MSE 50 mg/kg, and CPF-MSE 100 mg/kg. After the treatment phase, analyses were conducted on serum, ocular, and cerebral tissues. MSE100 and CPF-MSE100 normalized the pro-inflammatory markers (interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) and AChE serum levels. CPFMSE50 significantly enhanced these serum levels compared to CPF; however, it showed higher levels compared to the control. Moreover, the tissue analysis showed a significant decrease in oxidative stress (malondialdehyde (MDA) and nitric oxide (NO)) and an increase in antioxidant markers (glutathione (GSH), glutathione peroxidase (GSH-PX)), superoxide dismutase (SOD), and catalase (CAT) in the treated groups compared to CPF. Importantly, the significance of these effects was found to be dose-dependent, particularly evident in the CPFMSE100 group. We conclude that MSE has a promising therapeutic effect in the cerebral and ocular tissues of CPF-intoxicated mice, providing a potential solution for OP public health issues. [ABSTRACT FROM AUTHOR]

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990–0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ. [ABSTRACT FROM AUTHOR]

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation. [ABSTRACT FROM AUTHOR]

Benzocaine is a widely employed local anaesthetic; however, there is a notable dearth of preclinical and clinical evidence regarding its safety in ophthalmological products. To address this, a comprehensive strategy incorporating in silico and in vitro methodologies was proposed for assessing benzocaine's ocular toxicity without animal testing. To collect the in silico evidence, the QSAR Toolbox (v4.5) was used. A single exposure to two benzocaine concentrations (2% and 20%) was evaluated by in vitro methods. Hen's Egg Chorioallantoic Membrane Test (HET-CAM) was performed to evaluate the effects on the conjunctiva. To study corneal integrity, Short Time Exposure test (STE) and Bovine Corneal Opacity and Permeability (BCOP) assay, followed by histopathological analysis, were carried out. Results from both in silico and in vitro methodologies categorize benzocaine as non-irritating. The histopathological analysis further affirms the safety of using benzocaine in eye drops, as no alterations were observed in evaluated corneal strata. This research proposes a useful combined strategy to provide evidence on the safety of local anaesthetics and particularly show that 2% and 20% benzocaine solutions do not induce eye irritation or corneal damage, supporting the potential use of benzocaine in the development of ophthalmic anesthetic products. • Benzocaine is a possible local anesthetic to be used topically in eye drops. • Benzocaine acute eye damage was evaluated by a non-animal integrated approach. • 2% and 20% benzocaine solutions do not induce eye irritation or corneal corrosion. [ABSTRACT FROM AUTHOR]

Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision. While these complications remain rare, they are probably underreported. It is likely that both oncologists and ophthalmologists will come across MATs-associated ocular surface-adverse events in their practices, owing to the increasing number of patients being treated with MATs. Rapid identification of ocular surface-adverse events is crucial, as early intervention can manage these conditions to avoid vision loss and reduce negative impacts on quality of life. We discuss characteristics of ocular surface pathologies attributed to MATs, describe the suspected underlying pathophysiological mechanisms, and outline the main lines of treatment. • Immune checkpoint inhibitors can trigger many inflammatory ocular surface pathologies. • EGFR inhibitors can cause trichomegaly, keratitis, and corneal ulceration. • Antibody-drug conjugates induce vision-threatening corneal epitheliopathy. • Close communication between ophthalmologists and oncology specialists is required. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether low‐dose belantamab mafodotin (B‐MAF) dosing results in lower toxicity and better overall outcome. Methods: We retrospectively evaluated nine consecutive patients treated with low‐dose (1.9 mg/kg) B‐MAF. Results: The median age was 70 years. Most patients were penta‐refractory. Ocular toxicity was observed in 77.7%. Adverse events resulting in treatment delays were recorded in 9 out of 124 cycles being given. Overall response rate was 66% (6/9), and all responding patients achieved very good partial response or better. Within a median follow‐up of 12 (range 0.5–13.8) months, median progression‐free survival and overall survival were 14 (CI95% 6–22) and 20 (95%CI 0–41) months, respectively. Conclusion: Low‐dose B‐MAF regimen showed high‐efficacy and low‐toxicity profile. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a major public health issue in developing, often agricultural-based, tropical countries, which causes substantial mortality and morbidity. Most studies have been conducted on well-known toxic effects such as neurotoxicity, cytotoxicity, and hemotoxicity, however, there is scarce information on their indirect effects on the eye. In this review, we provide an overview of ocular pathologies caused by snakebite envenoming. In total, 65 cases, described in 42 case reports and series, were identified in the PubMed and Embase databases. Most reported ocular toxicities/disorders after snakebite envenoming were ophthalmoplegia (12 cases), intra- and peri-ocular hemorrhages (9 cases), and acute glaucoma (13 cases). We also discuss the possible mechanisms for these ocular pathologies. Interestingly, optic neuropathy might be an adverse effect of antivenom instead of directly being caused by envenoming. We prompt recognition of this largely overlooked topic within the field of snakebite, and further stress the need to combat this neglected tropical disease. [ABSTRACT FROM AUTHOR]

Background: Recurrent miscarriage (RM) refers to the unfortunate loss of pregnancy at least three times before the 20th week of gestation. The present study examined hydroxychloroquine (HCQ)'s therapeutic effects in recurrent miscarriage owing to potential positive outcomes like increased rate of live births and negative outcomes like ocular and retinal toxicity. Methods: The investigation involved the randomization of 400 mg of HCQ intervention in 91 pregnant women attending a monthly clinic at the Wenzhou TCM Hospital of Zhejiang Chinese Medical University. Results: According to the results, HCQ results in positive pregnancy outcomes, with improving rates of live births with continued use of the medication. At the same time, the results produced significant safety issues, including HCQ deposition in the retina and ocular toxicity. An investigation of HCQ's effects on the retinal nerve fiber layer measurements, ganglion cell layer measurements, and the inner plexiform layer measurements revealed a dynamic trend. Conclusion: We did not obtain conclusive outcomes regarding HCQ's effects on the changes in retinal measurements. However, the deposition of HCQ in the retina and the resulting vision loss, especially loss of color vision, stood out. These outcomes represent the safety and therapeutic effects of HCQ in pregnancy, posing concerns and creating the need for further studies. Interestingly, none of these outcomes were related to or dependent on the participants' age. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor (FGFR) inhibitors are an emerging class of small molecule targeted cancer drugs with promising therapeutic possibilities for a wide variety of malignancies. While ocular adverse events from FGFR inhibitors are reported in clinical trials, subsequent case studies continue to reveal new toxicities. Disease pathology affecting multiple parts of the eye has been reported, but the ocular surface and the retina are the most commonly encountered areas affected by FGFR inhibitors, manifesting as dry eye and FGFR inhibitor-associated retinopathy, respectively. Corneal thinning and melt is a rare but serious and potentially vision-threatening complication of FGFR inhibitor toxicity. Similarities between toxicities observed from other targeted cancer therapy drugs and FGFR inhibitors may help us understand underlying pathophysiological changes. The management of these adverse events requires close ophthalmologic follow-up and may require discontinuation of the offending agents in some cases. [ABSTRACT FROM AUTHOR]

Background: Although the side effects of chemotherapy are frequently described in research studies, there is little evidence on how common they are in everyday clinical care. This study's goal was to assess the most prevalent short-term side effects experienced by patients with localized breast cancer, undergoing chemotherapy based on anthracyclines and taxane-containing treatments, at the medical oncology department of the Mohammed VI University Hospital of Marrakech, Morocco. Methods: This was a descriptive study. We conducted a listening session at the outpatient department of the hospital with the help of a structured questionnaire. The session engaged 122 women who had undergone cycles of chemotherapy. A chi-square test was used to compare the incidence and relative risk of short side effects with both anthracycline and taxane-containing regimens. Results: The average age of participants was 49.1 years. In both regimens, the findings highlighted the frequency and relative risk of the following adverse effects: systemic symptoms (fever, asthenia and sleep disorder), gastrointestinal toxicity (Vomiting, nausea, diarrhoea, constipation, mucositis and loss of appetite), dermatological toxicity (Skin reactions on hands/feet, nail toxicity, allergies, alopecia and peripheral edema), neurological toxicity (neuropathy), arthromyalgia and ocular toxicity. Conclusions: In conclusion, it is crucial for healthcare professionals to be conscious of the significance of these adverse effects. They must also know how to manage them. Likewise, the listening approach highlights its importance in the daily follow-up and monitoring of patients. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class. [ABSTRACT FROM AUTHOR]

Studies comparing the ocular toxicity potential between legacy and alternative PFAS are lacking. To address this research gap, zebrafish larvae were exposed to both legacy PFAS (i.e., perfluorooctanesulfonic acid [PFOS] and perfluorooctanoic acid [PFOA]) and their corresponding alternatives (i.e., perfluorobutanesulfonic acid [PFBS] and perfluorobutanoic acid [PFBA]). Alterations in their visual behaviors, such as phototactic and optomotor responses (OMR), were assessed at sublethal concentrations. Gene expression variations in visual function-associated pathways were also measured. Visual behavioral assessment revealed that PFOS exposure resulted in concentration-dependent reductions in phototactic responses at 10–1000 μg/L, with PFOA exerting reduction effects only at 100 mg/L. However, their two alternatives had no effect at all tested concentrations. Following an improved contrast-OMR (C-OMR) assessment, PFOS decreased the OMR to a water flow stimulus at 10, 100, and 1000 μg/L. The gene expression analysis revealed that PFOS exposure markedly downregulated most genes involved in the opsins in the photoreceptor and phototransduction cascade, which explains the observed visual behavior changes well. Our findings indicate that PFOS is the most likely PFAS to cause visual toxicity, with PFOA present but less likely, and their substitutes, PFBS and PFBA, cannot be classified as visually toxic to zebrafish. [ABSTRACT FROM AUTHOR]

Phenylarsine oxide (PAO), an analog of lewisite, is a highly toxic trivalent arsenical and a potential chemical warfare agent. PAO-induced toxicity has been studied in lung, liver, and skin tissues. Nevertheless, very few studies have been published to comprehend the impact of PAO-induced toxicity on ocular tissues, even though eyes are uniquely vulnerable to injury by vesicants. Notably, arsenical vesicants such as lewisite have been shown to cause edema of eyelids, inflammation, massive corneal necrosis, and blindness. Accordingly, human corneal epithelial cells were used to study the effects of PAO exposure. PAO (100 and 200 nM) induced significant oxidative stress in corneal epithelial cells. Simultaneous treatment with N-acetyl- l -cysteine (NAC), an FDA-approved antioxidant, reversed the PAO-induced toxicity in human corneal epithelial cells. Furthermore, oxidative stress induction by PAO was accompanied by unfolded protein response (UPR) signaling activation and ferroptotic cell death. Further, to validate the findings of our in vitro studies, we optimized injury biomarkers and developed an ex vivo rabbit corneal culture model of PAO exposure. Investigations using PAO in ex vivo rabbit corneas revealed similar results. PAO (5 or 10 μg) for 3, 5, and 10 min caused moderate to extensive corneal epithelial layer degradation and reduced the epithelial layer thickness in a concentration- and time-dependent manner. Similar to human corneal cells, injuries by PAO in ex vivo cultured rabbit corneas were also associated with elevated oxidative stress, UPR signaling, and ferroptosis induction. NAC mitigated PAO-induced corneal injuries in rabbit ex vivo cornea culture as well. The reversal of PAO toxicity upon NAC treatment observed in our studies could be attributed to its antioxidant properties. These findings suggest that PAO exposure can cause significant corneal injury and highlight the need for further mechanistic studies to better understand the pathobiology of different arsenical vesicants, including PAO and lewisite. [Display omitted] • Optimized an ex vivo rabbit corneal injury model of PAO exposure. • PAO induces ROS and UPR in HCE-S cells and ex vivo rabbit corneas. • PAO induces ferroptosis in HCE-S cells and ex vivo rabbit corneas. • PAO causes severe pathophysiological injury in ex vivo rabbit corneas. • NAC counters PAO-induced toxicities in HCE-S cells and ex vivo rabbit corneas. [ABSTRACT FROM AUTHOR]

Purpose: The systemic and ocular pharmacokinetics (PK), and ocular toxicity of benzalkonium chloride (BAK)-free TearClear latanoprost ophthalmic solution, 0.005% formulation (TC-002) were evaluated. TC-002 is designed to selectively capture BAK at the time of drug administration; therefore, the dose delivered to the eye contains no quantifiable level of preservative. Methods: The systemic and ocular PK of TC-002 were compared to a BAK containing reference listed drug (RLD, Xalatan™) over a 24-h period, after a single topical ocular dose to 1 eye of male Dutch Belted (DB) rabbits (n = 3/timepoint). Latanoprost acid concentrations were measured in plasma and ocular tissues. The ocular toxicity was evaluated in a separate study and included toxicokinetic evaluation of TC-002 after once daily topical ocular dosing into each eye of DB rabbits (n = 8/group) for at least 28 days. Toxicity endpoints included ophthalmic and clinical evaluations, necropsy, and microscopic evaluation of ocular tissues. Results: Average ratios of Cmax values for TC-002/RLD ranged from 0.6 to 1.6, and Cmax and area under the concentration-time curve of last observed concentration (AUClast) exposures to latanoprost acid were similar (<2-fold) between the 2 treatments. In the 28-day study, the Tmax was achieved in both groups in <0.5 h. There were no abnormal ocular findings. Conclusions: TC-002 with no quantifiable preservative or BAK-containing RLD exhibited similar ocular and systemic PK profiles. TC-002 was well tolerated and comparable to RLD. TC-002 retains the safety and PK characteristics of RLD without the added concern of long-term exposure of the eye to preservatives. [ABSTRACT FROM AUTHOR]

Their improvement following treatment withholding was not significantly different (B); corneal epithelial changes following Belantamab therapy. Belantamab mafodotin-blmf: a novel antibody-drug conjugate for treatment of patients with relapsed/refractory multiple myeloma. Keywords: Belantamab mafodotin; Multiple myeloma; Corneal toxicity; Dry eye; Tear Film EN Belantamab mafodotin Multiple myeloma Corneal toxicity Dry eye Tear Film 3201 3204 4 10/24/23 20231101 NES 231101 Graph Findings Multiple myeloma (MM) is the second most prevalent hematological cancer and has a 5-year survival rate of 47% and a higher preponderance for males and the age group, 65-74 years [[1]]. [Extracted from the article]