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.

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.

Aim: The purpose of this study was to comprehensively explore the ocular toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. Materials & methods: Data were assembled from the US FDA\'s Adverse Event Reporting System (FAERS) database from 2017 to 2023. Information component and reporting odds ratio methods were used for signal detection in total/categorized CAR T-cell therapy. Results: A total of 17 positive signals (preferred term) were detected, yet none of them were documented in the product information. Some adverse events were with death outcomes and overlapped a lot with cytokine-release syndrome. Conclusion: The ocular adverse events associated with CAR-T cell therapy are noteworthy, and it is imperative to maintain increased alertness and institute early intervention strategies.
CAR-T-cell therapy is a highly effective treatment for blood cancers that has gained significant attention as a promising therapy in recent years. However, a complete analysis of its side effects on eyes has not been determined. In this study, we examined eye-related adverse events with five US Food and Drug Administration (FDA)-approved CAR T-cell therapies by using data from the FDA. We found that certain eye issues such as dilated pupils, impaired pupillary light reflex and eye surface bleeding deserve attention. Surprisingly, these problems were not mentioned in the product information. Since some adverse events can have severe outcomes, it is important to be vigilant and take early action.

BACKGROUND: Veterinary antiparasitic drugs are widely used in countries and regions in which parasitic diseases are endemic, which leads to the risk of accidental ingestion and poisoning in humans.  CASE PRESENTATION: A 40-year-old male patient with a history of cirrhosis sought medical attention on November 25, 2021, due to progressive vision loss. He had previously taken triclabendazole and bithionol and was diagnosed with toxic optic neuropathy on examination. Steroid, neurotonic, and high-pressure oxygen therapy were ineffective.
CONCLUSIONS: Triclabendazole and bithionol have potential risk of optic neurotoxicity and should be considered for enhanced supervision and warning labels.

Montmorillonite (Mt) and its derivatives are now widely used in industrial and biomedical fields. Therefore, safety assessments of these materials are critical to protect human health after exposure; however, studies on the ocular toxicity of Mt are lacking. In particular, varying physicochemical characteristics of Mt may greatly alter their toxicological potential. To explore the effects of such characteristics on the eyes, five types of Mt were investigated in vitro and in vivo for the first time, and their underlying mechanisms studied.
The different types of Mt caused cytotoxicity in human HCEC-B4G12 corneal cells based on analyses of ATP content, lactate dehydrogenase (LDH) leakage, cell morphology, and the distribution of Mt in cells. Among the five Mt types, Na-Mt exhibited the highest cytotoxicity. Notably, Na-Mt and chitosan-modified acidic Na-Mt (C-H-Na-Mt) induced ocular toxicity in vivo, as demonstrated by increases corneal injury area and the number of apoptotic cells. Na-Mt and C-H-Na-Mt also induced reactive oxygen species (ROS) generation in vitro and in vivo, as indicated by 2\',7\'-dichlorofluorescin diacetate and dihydroethidium staining. In addition, Na-Mt activated the mitogen-activated protein kinase signaling pathway. The pretreatment of HCEC-B4G12 cells with N-acetylcysteine, an ROS scavenger, attenuated the Na-Mt-induced cytotoxicity and suppressed p38 activation, while inhibiting p38 activation with a p38-specific inhibitor decreased Na-Mt-induced cytotoxicity.
The results indicate that Mt induces corneal toxicity in vitro and in vivo. The physicochemical properties of Mt greatly affect its toxicological potential. Furthermore, ROS generation and p38 activation contribute at least in part to Na-Mt-induced toxicity.

The purpose of this research was to explore the antifungal and anti-inflammatory effects of perillaldehyde (PAE) in Aspergillus fumigatus (A. fumigatus) keratitis and the underlying mechanism.
The biofilm formation, adherence assay, and propidium iodide uptake test were used to determine the possible mechanism of PAE in terms of antifungal effects in vitro. The severity of corneal infection was evaluated by clinical scores. The immunofluorescence staining (IFS) was adopted to detect the number of macrophages in infected corneas. Draize test was performed to assess the ocular toxicity of PAE. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot reflected the expression of inflammatory cytokines and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in mice corneas and RAW264.7 cells.
PAE was able to inhibit the formation of biofilm, reduce conidial adhesion, and damage the integrity of membranes to exert antifungal activity. In C57BL/6 mice models, PAE alleviated the severity of infected corneas, reduced the recruitment of macrophages and had low ocular toxicity. In addition, the mRNA and protein levels of TNF-α, CCL-2, and LOX-1 could be significantly decreased by the application of PAE after A. fumigatus infection in vivo and in vitro.
Our study indicated that PAE protected against A. fumigatus keratitis by reducing fungal load, accumulation of macrophages, and inhibiting the expression of inflammatory cytokines.

Pertuzumab is a recombinant anti-HER2 humanized monoclonal antibody widely used for the adjuvant treatment of HER2-positive breast cancer. Its safety is well established with the most common adverse effects being diarrhea and rash. To our knowledge, severe pertuzumab-induced ocular adverse events have never been reported. Herein, we describe several cases of pertuzumab/QL1209 (pertuzumab biosimilar)-induced blurred vision in healthy Chinese male subjects after a single injection of 420 mg pertuzumab/QL1209. Persistent optic nerve damage and vision loss occurred in the most severe case even after ophthalmic treatment. We conducted whole-exome sequencing (WES) of DNA samples from 5 cases and 13 controls to analyze the potential genetic factors and identified some associated variants (rs80303690 in RBM24, rs117375173 in CASR, rs1805097 in IRS2, and rs1227049 in CDH23). Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms gene enrichment analyses were carried out for differentially expressed genes clustered in the PI3K/AKT/mTOR and Ras/Raf/MAPK signaling pathways, which were exactly activated by HER2 phosphorylation. In summary, this is the first report describing the occurrence of ocular toxicity induced by pertuzumab in the Chinese population and exploring the possible genetic mechanisms. These findings could provide evidence for clinicians to raise concerns about the risk of ocular toxicity with the clinical use of pertuzumab.

By reviewing the recent articles regarding the ocular side effect of tamoxifen when treating breast cancer and glioma, this article summarized the incidence and the potential mechanism of the side effects of tamoxifen, and the specific ocular toxicity including keratopathy, cataract, retinopathy, optic neuropathy. This review would provide guidance for clinical ophthalmologists to early identify and appropriately manage tamoxifen induced ocular diseases. (Chin J Ophthalmol, 2021, 57: 232-236).
本文回顾总结了近年来他莫昔芬应用于乳腺癌、神经胶质瘤治疗时出现的相关眼部病变的文献，将他莫昔芬导致眼部病变出现的发生率、发病机制、相关眼部病变特征性表现（角膜病变、白内障、视网膜病变、视神经病变以及其他一些少见病变）进行综述，为眼科医师对他莫昔芬眼部病变的识别和眼部病变的监测提供指导。（中华眼科杂志，2021，57：232-236）.

BACKGROUND: We investigated structural injury patterns in the peripapillary retinal nerve fibre layer (p-RNFL) and ganglion cell inner plexiform layer (GCIPL) caused by ethambutol treatment.
METHODS: Sixty-four patients undergoing ethambutol treatment at Zhejiang Chinese Medicine and Western Medicine Integrated Hospital were recruited. Fourteen (14) exhibited visual dysfunction (abnormal group), and the remaining 50 had no visual dysfunction (subclinical group). The thickness of the p-RNFL, total macular retina layer and GCIPL were measured using Cirrus-HD Optical coherence tomography (Cirrus-HD OCT, Cirrus high-definition optical coherence tomography), and compared with 60 healthy, age-matched controls.
RESULTS: The p-RNFL thickness was similar in both subclinical and control groups. When compared with the control group, p-RNFL thickness in the abnormal group was significantly increased in the inferior and superior quadrants (GEE, P = 0.040, P = 0.010 respectively). In contrast with the subclinical group, p-RNFL thickness in the inferior quadrant was increased in the abnormal group (GEE, P = 0.047). The GCIPL thickness in the inferonasal and inferior sectors was significantly deceased in the subclinical group when compared with controls (GEE, P = 0.028, P = 0.047, respectively). The average and minimum value of GCIPL thickness, and thickness in the superonasal, inferior, inferotemporal, superotemporal and superior sectors were significantly decreased in the abnormal group when compared with controls (GEE, P = 0.016, P = 0.001, P = 0.028, P = 0.010, P = 0.012, P = 0.015, P = 0.010, respectively). The cube average macular thickness (CAMT) in the abnormal group was significantly thinner than controls (GEE, P = 0.027).
CONCLUSIONS: GCIPL measurements using Cirrus-HD OCT detected retinal ganglion cell layer loss following ethambutol treatment, before visual dysfunction occurred.