Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

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.

Toxic optic neuropathy associated with lamotrigine and levetiracetam dual therapy.

We report the case of an early adolescent male on lamotrigine and levetiracetam therapy with a 1-month history of progressive, bilateral, painless visual loss which resolved on cessation of lamotrigine. To our knowledge, we present the first case of lamotrigine and levetiracetam dual therapy associated with toxic optic neuropathy, supported by electrophysiology and optical coherence tomography (OCT) changes. Electrophysiology findings were consistent with retinal ganglion cell dysfunction, with bilateral optic nerve involvement. Macula OCT showed mild retinal ganglion cell loss in all inner quadrants bilaterally. This case highlights the importance of asking patients with epilepsy treated with lamotrigine and levetiracetam about visual problems and considering early dose reduction or cessation of treatment.

Visual Recovery Time in Patients with Ethambutol-induced Toxic Optic Neuropathy.

PURPOSE: We aimed to investigate the visual recovery time in patients with ethambutol-induced toxic optic neuropathy (EON) and identify the factors associated with the visual recovery time. METHODS: In this retrospective cohort study, we reviewed the medical records of 35 eyes from 35 patients with EON. Visual recovery was defined as a gain of three or more lines from the nadir. RESULTS: Patients were observed following discontinuation of ethambutol (EMB), with the mean follow-up period of 21.0 ± 16.0 months. The visual acuity at nadir was logarithm of the minimum angle of resolution 1.4 ± 0.4, and the final visual acuity was logarithm of the minimum angle of resolution 0.6 ± 0.5. Twenty-seven eyes (77.1%) showed significant visual recovery. In Kaplan-Meier survival, the mean estimated time for visual recovery was 15.2 ± 3.0 months, and 50% of the patients experienced visual recovery at 8.3 ± 2.2 months following EMB discontinuation. Multivariate Cox regression analysis identified several significant risk factors for delayed visual recovery, including duration of EMB medication ≤6 months, period from symptom onset to EMB discontinuation >14 days, and baseline peripapillary retinal nerve fiber layer thickness >98 µm. CONCLUSIONS: Our study indicated a mean time of visual recovery of 15 months for EON cases. Therefore, patients diagnosed with EON should be followed up for more than 1 to 2 years to evaluate their visual recovery. Delayed EMB discontinuation, short duration of EMB use, and initial peripapillary retinal nerve fiber layer thickening were associated with delayed visual recovery. Therefore, patients taking EMB should be followed up regularly for early detection of EON and immediate discontinuation of EMB to prevent severe damage to the optic nerve.

Ethambutol and its ophthalmic effects; is screening and collaboration the new way forward?

AIM: To screen patients on ethambutol and evaluate its role on visual functions and toxic optic neuropathy. SETTING AND DESIGN: Retrospective, observational single tertiary centre cohort of 80 patients. METHODS AND MATERIAL: A total of 69 from the initial 80 patients with visual complaints were categorised into two groups A and B; ongoing anti-tubercular therapy with ethambutol and having stopped ethambutol for greater than six months respectively. All patients underwent vision (V) testing on ETDRS chart and anterior and posterior segment evaluation. Additionally, patients in group A recorded color vision (CV) on Ishihara chart and visual evoked potential (VEP). STATISTICAL ANALYSIS USED: P value was calculated using Chi square test (SPSS ver. 20). RESULTS: Out of 69 patients in our study, 58 (84.05%) patients recorded reduced visual acuity. The mean visual acuity was 0.58 logMAR units. 33 out of our 58 (57%) patients with reduced visual acuity showed normal optic discs while 25 out of 58 (43%) showed altered optic discs. In group B, 14 out of 32 patients with vision of less than 20/20 also had optic disc pallor (p = 0.02). 12 out of 15 patients in group A recorded an altered color vision and also had a vision of less than 20/20 (p = 0.023). 15 patients who recorded altered VEP also had vision of less than 20/20 (p = 0.037). CONCLUSION: Visual acuity, color vision and vep are sensitive and sustainable tools which can be implemented in regular screening. Ethambutol toxicity is a real problem and a collaborative approach is necessary to establish screening protocols and prevent ethambutol induced toxic optic neuropathy.

Ocular toxicity associated with anti-HER2 agents in breast cancer: A pharmacovigilance analysis using the FAERS database.

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.

The Involvement of Unfolded Protein Response in the Mechanism of Nitrogen Mustard-Induced Ocular Toxicity.

Nitrogen mustard (NM) is a known surrogate of sulfur mustard, a chemical-warfare agent that causes a wide range of ocular symptoms, from a permanent reduction in visual acuity to blindness upon exposure. Although it has been proposed that the two blistering agents have a similar mechanism of toxicity, the mode of NM-induced cell death in ocular tissue has not been fully explored. Therefore, we hypothesized that direct ocular exposure to NM in mice leads to retinal tissue injury through chronic activation of the unfolded protein response (UPR) PERK arm in corneal cells and VEGF secretion, eventually causing cell death. We topically applied NM directly to mice to analyze ocular and retinal tissues at 2 weeks postexposure. A dramatic decline in retinal function, measured by scotopic and photopic electroretinogram responses, was detected in the mice. This decline was associated with enhanced TUNEL staining in both corneal and retinal tissues. In addition, exposure of corneal cells to NM revealed 228 differentially and exclusively expressed proteins primarily associated with the UPR, ferroptosis, and necroptosis. Moreover, these cells exhibited activation of the UPR PERK arm and an increase in VEGF secretion. Enhancement of VEGF staining was later observed in the corneas of the exposed mice. Therefore, our data indicated that the mechanism of NM-induced ocular toxicity should be carefully examined and that future research should identify a signaling molecule transmitted via a prodeath pathway from the cornea to the retina. SIGNIFICANCE STATEMENT: This study demonstrated that NM topical exposure in mice results in dramatic decline in retinal function associated with enhanced TUNEL staining in both corneal and retinal tissues. We also found that the NM treatment of corneal cells resulted in 228 differentially and exclusively expressed proteins primarily associated with ferroptosis. Moreover, these cells manifest the UPR PERK activation and an increase in VEGF secretion. The latter was also found in the corneas of the cexposed mice.

Ocular toxicities in chimeric antigen receptor T-cell therapy: a real-world study leveraging FAERS database.

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.

Evaluation of histologic, antiapoptotic and antioxidant effects of melatonin against the acute ocular toxicity of Cisplatin.

This study aimed to investigate the protective effect of melatonin against the acute toxicity of cisplatin in ocular tissues. The eyes of 40 rats were divided into 4 groups: Control group (10 rats), Melatonin (Mel) group (10 rats), Cisplatin (Cis) group (10 rats), Melatonin (Mel) + Cisplatin (Cis) group (10 rats). Retina, cornea, and ciliary body tissues were examined after hematoxylin-eosin staining of sections obtained from the eyes and were scored for disorganization and degeneration. Apoptotic cells were counted for the retina, cornea, and ciliary body with the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) method. The total antioxidant status (TAS) / total oxidant status (TOS) of homogenized eye tissues were measured. While apoptotic cells were found to increase in the cornea of the Cisplatin (Cis) group, no difference was found regarding the retina and ciliary body cell count. An increased number of apoptotic cells in the cornea of the Cis group was found while there was a decrease in the group where Cisplatin and Melatonin were administered together (Mel+Cis group). There was no statistically significant difference amongst groups for TOS or TAS. Melatonin had a partial protective effect against histological damage.

Pharmacokinetic and Ocular Toxicity Evaluation of Latanoprost Ophthalmic Solution, 0.005%, with Preservative Level Reduced to Below the Limit of Quantitation.

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.

Ocular toxicities associated with antibody drug conjugates and immunotherapy in oncology: clinical presentation, pathogenesis, and management strategies.

INTRODUCTION: The development of molecularly targeted anticancer therapies and immunotherapy continues to revolutionize the treatment of cancer. FDA accelerated approvals of novel targeted therapies allowed for introduction of these agents into the clinic at a rapid rate. On-and off-target ocular toxicities are prevalent treatment-related adverse events of newer therapies including antibody drug conjugates (ADCs) and immunotherapy. Ocular toxicities associated with ADCs and immunotherapy have heterogeneous presentations and pathogenesis requiring unique and often complex monitoring, and management. AREAS COVERED: In this article, we provide an updated review of treatment-emergent ocular toxicity associated with new and novel oncologic therapies and summarize guidelines and best practice strategies for prevention, monitoring and management. A literature search was performed through PubMed, ClinicalTrials.gov, and FDA website (1 January 2017 to 10 May 2023) to identify relevant information. EXPERT OPINION: The implementation of a strategy for monitoring, prevention, and management of treatment-related ocular toxicities involves a multi-disciplinary, often cross-center approach. Communication with infusion nursing leadership, clinic staff, and eye care providers is crucial to the successful implementation of eye care plans to prevent and manage ocular toxicity.

Antibody-Drug Conjugates and Ocular Toxicity.

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.

Veterinary deworming agent-induced toxic optic neuropathy: a case report.

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.

Cyclopentenylcytosine (CPE-C): In Vitro and In Vivo Evaluation as an Antiviral against Adenoviral Ocular Infections.

Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral activity was evaluated in vitro using standard plaque reduction assays to determine the 50% effective concentrations (EC50s) and in vivo in the Ad5/NZW rabbit ocular replication model. Ocular toxicity was determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ranged from 0.03 to 0.059 µg/mL for nine adenovirus types that commonly infect the eye. Ocular toxicity testing determined CPE-C to be non-irritating or practically non-irritating by Draize scoring. In vivo, 3% CPE-C topically administered 4X or 2X daily for 7 days to adenovirus-infected eyes demonstrated effective antiviral activity compared with the negative control and comparable antiviral activity to the positive control, 0.5% cidofovir, topically administered twice daily for 7 days. We conclude CPE-C was relatively non-toxic to rabbit eyes and demonstrated potent anti-adenoviral activity in vitro and in vivo.

Ocular involvement in allergic drug reactions.

PURPOSE OF REVIEW: Many systemic medications have been observed to cause ocular toxicity. A subset of these reactions is thought to involve immunomodulation or a hypersensitivity reaction. As new medications are developed, ocular adverse effects are becoming increasingly prevalent. Herein we review immune-mediated drug reactions affecting they eye with special attention to the hypersensitivity mechanisms leading to ocular toxicity. RECENT FINDINGS: Recent work has focused on mechanisms and risk of immune-mediated ocular adverse drug reactions including genetic susceptibility and loss of ocular immune privilege. SUMMARY: Given the consequences of immune-mediated ocular adverse drug reactions, clinicians must be aware of these to facilitate early recognition and management. The prompt involvement of an ophthalmologist for diagnosis and management is often essential to preserve vision and avoid long-term morbidity.

[Ethambutol-induced toxic optic neuropathy during treatment of tuberculosis meningitis in a child]. / Neuropathie optique toxique à l'éthambutol au cours d'une méningite tuberculeuse chez un enfant.

INTRODUCTION: Toxic optic neuropathy is a severe optic nerve injury that can compromise the prognosis for vision, justifying early clinical and ancillary diagnosis. CASE DESCRIPTION: We report the case of an 11-year-old child being treated for tuberculous meningitis with a combination of ethambutol and three other anti-bacillary drugs, referred for a rapidly progressive bilateral decline in visual acuity. On ophthalmologic examination, the visual acuity was counting fingers within 1ft in both eyes, and bilateral optic disc pallor was noted, without other associated abnormalities. Neurological imaging was unremarkable, with red-green dyschromatopsia and a bilateral cecocentral scotoma. Faced with this clinical and paraclinical picture, we arrived at the diagnosis of ethambutol toxic optic neuropathy, with a multidisciplinary decision leading to a change in the antibacillary treatment protocol. No clinical improvement was noted after 3 months of follow-up. DISCUSSION: Optic nerve toxicity is rare in children and is classically described as dose- and time-dependent. CONCLUSION: Ethambutol ocular toxicity is extremely rare in children, and the required action when detected is to discontinue the drug. Reversibility is not always assured, which requires early detection of toxic optic neuropathy by close clinical and ancillary monitoring and, above all, sensitization of the treating physicians (pediatricians, pulmonologists and neurologists).

FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer.

On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx for treatment of adult patients with folate receptor-α (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic therapies. The VENTANA FOLR1 (FOLR-2.1) RxDx Assay was approved as a companion diagnostic device to select patients for this indication. Approval was based on Study 0417 (SORAYA, NCT04296890), a single-arm, multicenter trial. In 104 patients with measurable disease who received mirvetuximab soravtansine-gynx, the overall response rate was 31.7% [95% confidence interval (CI), 22.9-41.6] with a median duration of response of 6.9 months (95% CI, 5.6-9.7). Ocular toxicity was included as a Boxed Warning in the U.S. Prescribing Information (USPI) to alert providers of the risks of developing severe ocular toxicity including vision impairment and corneal disorders. Pneumonitis and peripheral neuropathy were additional important safety risks included as Warnings and Precautions in the USPI. This is the first approval of a targeted therapy for FRα-positive, platinum-resistant ovarian cancer and the first antibody-drug conjugate approved for ovarian cancer. This article summarizes the favorable benefit-risk assessment leading to FDA's approval of mirvetuximab soravtansine-gynx.

Dietary Alcohol Consumption Elicits Corneal Toxicity Through the Generation of Cellular Oxidative Stress.

Purpose: Clinical data suggest that alcohol use is associated with the development of signs and symptoms of dry eye disease. However, preclinical data investigating ocular toxicity after dietary alcohol consumption are lacking. In this study, we investigated the effects of alcohol on the ocular surface, in human corneal epithelial cells (HCE-T) in vitro and in C57BL/6JRj mice in vivo. Methods: HCE-T were exposed to clinically relevant doses of ethanol. To determine the effects of dietary alcohol consumption in vivo, wild-type mice were administered the Lieber-DeCarli liquid diet (5% vol/vol ethanol or isocaloric control) for 10 days ad libitum. Corneal fluorescein staining was performed to assess ocular surface damage. Histopathological and gene expression studies were performed on cornea and lacrimal gland tissue. Results: Sublethal doses of ethanol (0.01%-0.5%) resulted in a dose-dependent increase of cellular oxidative stress in corneal epithelial cells and a significant increase in NFE2L2 and downstream antioxidant gene expression, as well as an increase in NFκB signaling; short-term exposure (0.5%, 4 h) triggered significant corneal epithelial cell barrier breakdown. Exposure to the alcohol-containing diet caused a 3-fold increase in corneal fluorescein staining, with no effect on tear volumes. Corneal thickness was significantly reduced in the alcohol diet group, and corneal tissue revealed dysregulated antioxidant and NFκB signaling. Our data provide the first published evidence that alcohol exposure causes ocular toxicity in mice. Conclusions: Our results are consistent with clinical studies linking past alcohol consumption to signs of ocular surface disease.

ROS generation and p-38 activation contribute to montmorillonite-induced corneal toxicity in vitro and in vivo.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

Management of Belantamab Mafodotin-Associated Keratopathy With Rigid Gas-Permeable Corneal Contact Lenses.

ABSTRACT: Belantamab mafodotin is a relatively new drug used in the treatment of relapsed or refractory multiple myeloma. Clinical studies have shown promising responses, but ocular toxicity remains a major challenge with dose reduction or therapy discontinuation being the only available treatment option. We report a clinical case of a patient with severe keratopathy under therapy with belantamab. The use of rigid gas-permeable corneal contact lenses led to a major visual improvement and enabled therapy continuation at full dose over several months. Although this strategy may not be suitable for all patients, it provides an additional option for the treatment of ocular toxicity of this promising agent.

Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation.

The aim of this study was to investigate the molecular, biochemical, and histopathological effects of bromelain, which has antioxidant and anti-inflammatory properties, against cisplatin-induced ocular toxicity. The groups were designed as (1) Control, (2) Cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Bromelain (50 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Bromelain (100 mg/kg, orally for 14 consecutive days). The activity of total antioxidant capacity (TAC) and total oxidant status (TOS) and levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1ß (IL-1ß), IL-10, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and 8-OHdG were measured in ocular tissue. The mRNA expression of NF-κB and Caspase-3 was also evaluated. Also, ocular sections were evaluated histopathologically. Bromelain demonstrated a dose-dependent protective effect in cisplatin-induced toxicity by regulating oxidative stress, inflammation, and tissue damage. Our results suggested that bromelain may be a potential adjuvant that can protect the eye from cisplatin-induced toxicity.