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Purpose of Review: Cancer immunotherapy is one of the most emerging and rapidly growing fields.Ocular side effects associated with these therapies are common and can be present in up to 70% of patients.The cornea may be involved in different pathogenic mechanisms triggered by different immunotherapeutic agents, and corneal disease varies from mild symptoms to severe corneal ulceration and melting with visual loss.We aimed to review the incidence, mechanism, and management of ocular surface side effects in cancer patients receiving immunotherapy., Recent Findings: With the recent use of immunotherapeutic agents in cancer patients, in particular immune checkpoint inhibitors (ICIs) and epidermal growth factor receptor (EGFR) inhibitors, ocular surface and corneal involvement are common side effects.These patients can be at risk of sight threatening complications that warrant prompt diagnosis and careful monitoring and management., Summary: Immunotherapy- related corneal complications in cancer patients are associated with a decreased quality of life. Prompt recognition and an interdisciplinary approach between ophthalmologists and oncologists are crucial to handle immune related ocular adverse events in these patients, in order to maintain ocular surface integrity and avoid a vision threatening complication., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to investigate the relationship between diclofenac sodium ophthalmic solution (DFNa) and corneal epithelial cell damage and to evaluate the preventive effect of rebamipide (RBM) on it. Methods: DFNa, DFNa/preservative-free (PF), or 0.5% chlorobutanol (CB) solution was instilled into the conjunctival sac of a normal rabbit eye, and corneal resistance measurement (using a corneal resistance device [CRD]) was performed 120 min after the end of instillation. Then, fluorescent staining (FL), corneal tissue staining (hematoxylin and eosin [H&E]), and immunostaining (zona occlusion-1) were performed (RBM-untreated group). However, RBM was instilled into the eyes of another group of normal rabbits, followed by each of the solutions; 120 min after the end of instillation, all evaluations were performed for this group (RBM treatment group). Results: Using the CRD method, in the RBM-untreated group, corneal resistance (CR; %) was found to be significantly reduced in DFNa (79.9 ± 19.4%), DFNa/PF (89.1 ± 17.3%), and 0.5% CB (83.8 ± 10.6%). In addition, DFNa and 0.5% CB solutions showed positive staining in the FL staining method. In the H&E staining method, some clear voids were observed in the outermost layer of the cornea using DFNa and 0.5% CB solutions. However, corneal epithelial damage was suppressed in the RBM treatment group. ZO-1 immunostaining in DFNa and 0.5% CB solutions revealed discontinuous localization of ZO-1 at the cell periphery. Conclusions: RBM eye drops were effective in preventing corneal epithelial damage caused by DFNa eye drops, and CB was considered to be the main causative agent of this damage.

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

Background: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate., Methods: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control., Results: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples., Conclusion: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To report the case of a 75-year-old patient who presented crystalline keratopathy secondary to the use of topical ciprofloxacin with histopathological verification, after cataract surgery without complications., Method: Case report with clinical and photographic follow-up, as well as slides with samples of epithelium and crystalline deposits., Results: Corneal deposits resolved after drug suspension, topical lubricant change, and subsequent surgical debridement. The histopathological examination reported epithelial cells and basophilic particles compatible with drug precipitates., Conclusions: Crystalline keratopathy is a condition in which crystals of various kinds are deposited in the corneal epithelium and/or in the anterior stroma. It may have an infectious, pharmacological cause or, in rarer cases, corneal dystrophies. Certain factors such as a previous epithelial defect, systemic pathology with diabetes mellitus, ocular surgery and previous dry eye can favor the deposition of ciprofloxacin leading to the formation of a keratopathy., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL or 5 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1, 3, 7, 14, and 28 for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation was used to examine corneal cross-sections collected at the completion of follow-up. Following exposure, mice experienced central corneal epithelial erosion and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma in both dosages. The epithelium was recovered by day 3 in the low dose group, followed by exacerbated punctuate erosions alongside persistent corneal edema that arose and continued onward to four weeks post-exposure. The high dose group showed persistent epitheliopathy throughout the study. The endothelial cell density was reduced, more prominent in the high dose group, early after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at 4 weeks post-exposure included dysmorphic basal epithelial cells and reduced epithelial thickness, and in the limbal cornea included decreased cellular layers. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Intravitreal methotrexate injection (400 µg/0.1 mL) is the current mainstay for managing vitreoretinal lymphoma. Various complications associated with intravitreal methotrexate are cataract, keratopathy, maculopathy, sterile endophthalmitis, optic atrophy, vitreous haemorrhage, etc. The most common adverse effect of intravitreal methotrexate is keratopathy occurring in more than half of cases. The severity may range from diffuse punctate keratopathy to severe epitheliopathy leading to photophobia, pain, visual blurring, epiphora, etc. This may become a reason for reduced compliance with treatment. The management of these complications includes oral folic acid, topical folinic acid supplementations and reduced frequency or cessation of methotrexate intravitreal injections. Here, we report a simple method of eyewash in a large amount of balanced salt solution after the intravitreal injection procedure to reduce the severity of keratopathy, which helped the patient tolerate the treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries., Methods: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye.", Results: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging., Conclusions: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The authors describe two cases of corneal ocular surface squamous neoplasia (OSSN), presenting at our rural eyecare centre, which were initially misdiagnosed as viral epithelial keratitis and corneal pannus with focal limbal stem cell deficiency. Both the cases were refractory to initial treatment and corneal OSSN was suspected. Anterior segment-optical coherence tomography (AS-OCT) revealed a thickened, hyper-reflective epithelium with abrupt transition and an underlying cleavage plane, features typical of OSSN. Topical 1% 5-fluorouracil (5-FU) therapy was initiated and in two cycles (first case) to three cycles (second case), complete resolution was noted both clinically and on AS-OCT, with no significant side effects. Both patients are currently free of tumour at the 2-month follow-up period. The authors report the rare, atypical presentations of corneal OSSN, discuss the masquerades and highlight the role of primary topical 5-FU in managing corneal OSSN in limited resource settings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Drug-induced keratopathy occurs when the use of certain drugs, particularly ophthalmic preparations, causes pathological changes in the cornea. These changes can be related to the toxic effects of the drugs themselves or drug preservatives. The disease is characterized by a range of clinical features and lacks specific diagnostic criteria, which can lead to misdiagnosis and inappropriate treatment. In order to address these challenges, the Cornea Group of the Ophthalmology Branch of the Chinese Medical Association has brought together leading experts in the field to review key techniques for the diagnosis and treatment of drug-induced keratopathy. As a result, they have developed this consensus to guide the prevention and treatment of this condition.

Competing Interests: D. B. is a consultant and speaker for Novartis and Bayer, and a consultant for Alcon. S. S., D. R. M., T. H., A. B., M. R. J. W., S. A. Z., and F. B. declare no conflicts of interest related to the topic.

Ocular injuries following sulfur mustard (SM) exposure are characterized by an acute phase expressed by corneal erosions and inflammation of the anterior segment that after a clinically silent period may be followed by irreversible corneal injuries. The latter includes epithelial defects, chronic inflammation and neovascularization (NV), and were defined in rabbits and in humans as Limbal Stem Cell Deficiency (LSCD), that derived from a delayed loss of corneal epithelial stem cells (ESC), due to secondary processes most likely in the epithelial stem cell (SC) niche. The present study expands our research on SM-induced ocular injury to rodents (rats and mice) following whole body vapor exposure, aiming to define whether the delayed development of LSCD is a general characteristic of SM ocular toxicity. Freely moving rats and mice were exposed to SM vapor (155 μg/l, 10 min). Clinical examination was carried out in rats and included a slit-lamp bio-microscopy, up to 6 months. Eyes were taken for histology at different time points following exposure and evaluation included hematoxylin and eosin (H&E) staining for general morphology, PAS for identification of goblet cells and p63 immunohistochemistry for progenitor epithelial cells. Whole body exposure to SM vapor in rats and mice resulted in acute ocular injury characterized by corneal erosions and ocular inflammation. Following a brief recovery period, 80-90% of the exposed eyes developed corneal NV associated with abnormal corneal epithelium, stromal inflammation and endothelial damage. The late injury was accompanied by migration of conjunctival goblet cells to the cornea and a loss of limbal epithelial progenitor cells, indicating LSCD. The long-term ocular injury shown hereby in rats and mice was consistent with the lesions described in rabbits and in human casualties and demonstrated the general phenomenon of limbal epithelial stem cells deficiency in SM ocular toxicity. The delayed manifestation of this pathology points towards a therapeutic window for the development of medical countermeasures in small animals following exposure in a real life scenario., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to report a case of acute corneal endothelial decompensation caused by a topical dorzolamide/timolol fixed combination (DTFC) after Descemet stripping automated endothelial keratoplasty., Methods: A 75-year-old woman who was referred to our hospital with a chief complaint of visual disturbance in the right eye after cataract surgery. Anterior segment optical coherence tomography identified an extensive defect in Descemet membrane. The patient subsequently underwent uneventful Descemet stripping automated endothelial keratoplasty surgery for persistent corneal edema. Two weeks after surgery, she had been prescribed topical DTFC twice daily to control elevated intraocular pressure. On the day she started using the eye drops, the patient noticed an acute deterioration of visual acuity. Severe corneal edema was detected at follow-up 5 days later., Results: The topical DTFC was stopped immediately. Thereafter, the corneal edema improved gradually, and there was a reduction in corneal thickness., Conclusions: Topical DTFC should be used with caution after corneal endothelial transplantation because of the possibility of iatrogenic corneal endothelial dysfunction., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this article is to report 3 cases of corneal allograft rejection that occurred in temporal proximity to administration of the zoster subunit vaccine (RZV)., Methods: Three cases of corneal transplant rejection that developed after RZV administration were identified. Clinical history, including existence of other risk factors, timing of rejection, corticosteroid therapy at the time of onset of rejection, and course were reviewed., Results: The onset of symptoms occurred 5 weeks after the first RZV dose in 1 patient and 1 and 6 weeks after the second dose in the other 2 patients. Coexisting risk factors included history of endothelial keratoplasty in the fellow eye in 1 patient and previous failure of a penetrating keratoplasty because of rejection in a second patient. The third patient had a history of 1 episode of rejection in a previous graft that resolved and then experienced graft failure over several years. In 2 patients, rejection developed despite relatively high levels of topical steroid therapy: prednisolone acetate 1%, 4 × per day in 1 patient and difluprednate 0.05%, 3 × per day in a second patient., Conclusions: RZV, which elicits a more robust immune reaction than the zoster live-attenuated vaccine, ZVL, may increase the risk of allograft rejection in immunocompetent patients with preexisting corneal endothelial or penetrating transplants. Based on the available data, it may be reasonable to increase the topical corticosteroid regimen before the first dose, until approximately 3 months after the second dose of ZVL., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate the corneal toxicity of intravitreal methotrexate used for the prevention of proliferative vitreoretinopathy (PVR)., Methods: In this retrospective case series, eyes with recurrent retinal detachment secondary to PVR were treated with intravitreal injections of 400 μg methotrexate at an average frequency of every 7 days after vitrectomy with silicone oil tamponade. Corneas were examined for corneal epitheliopathy by slit-lamp biomicroscopy before each injection., Results: Thirteen eyes of 12 patients were reviewed. All had a history of recurrent retinal detachment secondary to PVR treated with vitrectomy and silicone oil. The median age was 35 years (range: 9-83). Four patients (33%) were female. The median follow-up duration was 8 weeks (range: 5-10). The median BCVA (logMAR notation) was 2.00 preoperatively, 2.00 at 1 month postoperatively, and 2.00 at the most recent follow-up (P = 0.969). Ten eyes (77%) were pseudophakic. Nine eyes (69%) had a preexisting ocular comorbidity. The median number of injections was 8 (range: 5-10). The median interval time between each injection was 7.0 days (range: 5.8-10.5), and the median follow-up period beyond last injection was 16 weeks (range: 8-28). Two eyes (15.4%) developed mild corneal epitheliopathy during the course of the treatment., Conclusions: Most eyes in this small series tolerated methotrexate injections without corneal toxicity. In eyes that developed epitheliopathy, the findings were mild and not treatment-limiting., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Patients receiving chemotherapy may experience ocular discomfort and dry eye-like symptoms; the latter may be neuropathic in nature. This study assessed corneal and somatic hypersensitivity in male rats treated with paclitaxel and whether it was relieved by nicotinamide riboside (NR)., Methods: Corneal sensitivity to tactile and chemical stimulation, basal tear production, and sensitivity of the hindpaw to tactile and cool stimuli were assessed before and after paclitaxel in the absence and presence of sustained treatment with 500 mg/kg per os NR. Corneal nerve density and hindpaw intraepidermal nerve fiber (IENF) density were also examined., Results: Paclitaxel-treated rats developed corneal hypersensitivity to tactile stimuli, enhanced sensitivity to capsaicin but not hyperosmolar saline, and increased basal tear production. Corneal nerve density visualized with anti-β-tubulin or calcitonin gene-related peptide (CGRP) was unaffected. Paclitaxel induced tactile and cool hypersensitivity of the hindpaw and a loss of nonpeptidergic hindpaw IENFs visualized with anti-protein gene product (PGP) 9.5 and CGRP. NR reversed tactile hypersensitivity of the cornea without suppressing tear production or chemosensitivity; it did not alter corneal afferent density. NR also reversed tactile and cool hypersensitivity of the hindpaw without reversing the loss of hindpaw IENFs., Conclusions: These findings suggest that paclitaxel may be a good translational model for chemotherapy-induced ocular discomfort and that NR may be useful for its relief. The ability of NR to relieve somatic tactile hypersensitivity independent of changes in sensory nerve innervation suggests that reversal of terminal arbor degeneration is not critical to the actions of NR.

Background: Drug reaction with eosinophilia and systemic symptoms, known as DRESS syndrome, is a rare drug induced hypersensitivity reaction syndrome., Methods: case resport., Results: We describe a patient who presented with acute erythematous rash on her face, fever>38ºC, lymphadenopathy, blood abnormalities, and reaction suspected to be amoxicillin clavulanate-related. The patient also had an associated bilateral redness of the conjunctiva, peripheral corneal infiltrates, and anterior chamber with 3+ cells., Conclusion: We describe the first occurrence of bilateral marginal corneal infiltrates and acute anterior uveitis associated with amoxicillin clavulanate-induced DRESS syndrome and discuss its pathogenesis.

Palytoxin (PTX) is produced by corals such as zoanthid corals. Here we present a case of bilateral PTX-induced keratoconjunctivitis. A 63-year-old man presented to the emergency department with symptoms of red eye, purulent discharge, and foreign body sensation in both eyes. On slit lamp examination, epithelial defects in both eyes with a ring-shaped corneal stromal infiltrate in the right eye and a marginal stromal infiltrate in the left eye were noted. High-resolution anterior segment optical coherence tomography (HR-AS-OCT) showed stromal hyperreflectivity and Descemet folds. Bacterial, fungal, and amoebic cultures were taken. Empirical treatment with topical dexamethasone as well as antibiotics and systemic doxycycline was started. The next day the patient stated that he had been handling zoanthid coral without gloves and had rubbed his eyes afterward. Bilateral PTX-induced keratoconjunctivitis was diagnosed. His eyes were irrigated abundantly with saline solution, and umbilical cord serum eye drops were added to the treatment. Treatment was tapered according to improvement of the corneal infiltrates and epithelial defects. After four months, the stromal infiltrates were resolved but corneal scars persisted in both eyes. HR-AS-OCT showed anterior stromal hyperreflectivity corresponding to corneal leucomas. PTX can cause ocular adverse effects such as keratolysis and corneal inflammation, and in some cases can lead to corneal perforation. It can also produce systemic adverse effects, hence the importance of the preventive measures when handling corals that can produce this toxin.

Background: New targeted antibody-drug conjugates (ADCs) against multiple myeloma are known to induce adverse effects that may lead to treatment discontinuation. Preclinical studies reported early severe ocular damage related to the use of belantamab mafodotin (belamaf), including ocular surface inflammation, severe dry eye, and a specific toxicity to the cornea, namely microcystic keratopathy. While belamaf-induced ocular changes have not been prospectively studied, a better understanding of mechanisms involved as well as kinetics may aid in anticipating dose adjustment rather than stopping the treatment once clinical ocular damage is too severe., Case Presentation: A 61-year-old woman scheduled for belamaf as a fifth-line treatment against multiple myeloma was prospectively included. Clinical examinations were performed before and every 3 weeks afterward, together with in vivo confocal microscopy (IVCM) of the cornea. Visual acuity, symptoms, slit-lamp examination, and ultrastructural changes of the cornea were recorded according to the received dose of belamaf. More precisely, kinetics, shape, density, and location of the toxic corneal lesions have been followed and analyzed using IVCM. Also, specific lesions at the sub-basal nerve plexus layer were detected and characterized for the first time. This advanced approach allowed a better understanding of the belamaf-induced toxicity, further balancing the dose to maintain good vision and eye health while continuing the treatment., Conclusions: Systematic ultrastructural analysis and follow-up of the corneal state during ADCs treatment for multiple myeloma may open new avenues in the therapeutic approach. Early preclinical detection of ocular damage may accurately contribute to finding the correct dose for each patient and not stopping the treatment due to severe ocular adverse effects., (© 2021. The Author(s).)

Purpose: The purpose of this study is to report a case of corneal epithelial defects resulting from topical treatment of blepharitis with tea tree oil (TTO)., Methods: A 44-year-old man with a 1 year history of blepharitis non-responsive to eyelid hygiene was found to have signs of Demodex infestation. He was treated with a topical, off-label 50% TTO solution. Shortly afterward, the patient complained of bilateral ocular discomfort., Results: Slit-lamp examination revealed conjunctival injection and a corneal epithelial defect in both eyes. Treatment with lubricant, antibiotic, and steroid eye drops as well as bandage contact lenses was required to facilitate corneal healing., Conclusions: Topical use of off-label, 50% concentration TTO can result in corneal epithelial defects. Eye care professionals should remain aware of this risk and only use approved, low-concentration TTO products when treating Demodex-related blepharitis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Cisplatin is a widely used and highly effective anti-cancer agent and one of the limiting side effects of cisplatin is ocular toxicity. Achillea millefolium , also known as yarrow, is a plant that has been used for many years to treat various health problems including chemotherapy-related toxicities. Methods: The present investigation was designed to evaluate the biochemical, molecular and histopathological effects of Achillea Millefolium on cisplatin-induced oxidative and inflammatory ocular damage in rats. Twenty-four adult male rats were assigned randomly to four groups ( n = 6 ) as (1) control, (2) cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Achillea millefolium (200 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Levels of total antioxidant capacity and total oxidant status, SOD, MDA, IL-1β, and IL-10 were measured in ocular tissue. The mRNA expressions of TNF-α, nuclear factor kappa B and Caspase-3 were evaluated. Also, ocular sections were evaluated histopathologically. Results: Achillea Millefolium upregulated ocular antioxidant enzymes and downregulated inflammation. The SOD activity and total antioxidant capacity increased whereas total oxidant status and MDA levels decreased significantly at high dose group. High dose Achillea millefolium treatment reduced the IL-1β concentrations, whereas IL-10 levels increased significantly in that group. Moreover, we observed that Achillea millefolium restored ocular histopathological structure and significantly suppressed apoptosis by reducing the expression of Caspase-3. Conclusion: Collectively, our results suggest that Achillea millefolium have protective effects against cisplatin-induced ocular toxicity and is a promising adjuvant therapy with the potential to prevent cisplatin related ocular toxicity.

Studies have reported that the incidence of ocular discomfort in people who often wear makeup is higher than that in the normal population. The incidence of ocular discomfort of these people may be also related to the daily ocular exposure to chemical surfactants during cleaning. The objectives of this study were to explore morphological and pathological changes in the murine ocular surface after low-dose repeated exposure to disodium cocoamphodiacetate (DC), a kind of chemical surfactant widely used in personal cleaning products, and to investigate the possible mechanisms. DC was administered in low dose (0.1%) to the ocular surface of C56BL/6 once daily for two weeks. We found that there were an increase of sodium fluorescein staining on the cornea, a significant thinning of corneal epithelial thickness, and increased TUNEL-positive cells in corneal epithelium in vivo. DC treatment also modulated the distribution of K14 + and P63 + epithelia from the limbal to the center on the cornea. In cultured murine corneal epithelial progenitor cell line (TKE2), DC treatment induced cell detachment and decreased the activation of Ak strain transforming protein (AKT), and extracellular signal-regulated kinase (ERK). And DC increased TUNEL-positive cells in vitro with increased expression of cleaved Caspase3 and B-cell lymphoma-2 associated X protein (Bax). Our results indicated that repeated low-dose DC exposure on ocular surface caused significant impairment on the structure and viability of the corneal epithelium by inhibiting epithelial proliferation and inducing apoptosis. It provides the foundations to understand the harmful effects of cleaning products daily exposure on the ocular surface., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Vitreo-retinal lymphoma (VRL) is the most common intraocular lymphoma and is highly associated with central nervous system (CNS) lymphoma (CNSL), both posing a therapeutic challenge. We investigated patients' characteristics, efficacy and safety of intravitreal methotrexate (MTX) injections and their outcomes over 20 years. The records of 129 patients diagnosed between 1997 and 2018 were retrospectively reviewed. Lymphoma involved both the CNS and vitreo-retina (49%), solely the CNS (37%) or solely the vitreo-retina (14%). In all, 45·5% of the patients with CNSL either presented with VRL or developed it after a mean (±SE) of 85·7 (7·3) months. In all, 66·0% of the patients diagnosed with VRL either presented with CNSL or developed it after a mean (±SE) 42·6 (7·6) months. The 81 patients with VRL (134 eyes) received a mean (±SD) of 19 (7) injections; however, only 5 (4) injections were needed to reach complete remission. Local recurrence occurred in two of the 81 patients. Overall, 80·2% of eyes had an initial moderate-severe visual loss, and >50% of them improved. Reversible keratopathy was the most prevalent side-effect. A total of 18·5% developed intraocular pressure (IOP) elevation due to angle neovascularisation after 16 injections, which could be reversed with prompt intravitreal injection of bevacizumab. Intravitreal MTX injections are a safe and effective treatment for VRL. Fewer injections (15) may offer similar results with fewer side-effects., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: To describe the management and outcome of an ocular surface alkali burn in the setting of previous laser in situ keratomileusis (LASIK)., Methods: This is a case report and review of relevant literature., Results: A 25-year-old man with a history of LASIK presented 4 weeks after a sodium hydroxide splash to his left eye with visual acuity of 20/60 and a nonhealing epithelial defect adjacent to sectoral inferior limbal ischemia in the setting of trichiasis from upper eyelid cicatricial entropion. After topical corticosteroids were discontinued following the repair of the entropion, the patient returned 3 days later with worsening vision and severe diffuse lamellar keratitis with the melting of the LASIK flap. After promptly lifting the flap and debriding the interface, inflammation was managed with oral, instead of topical, corticosteroids. Over several weeks, the epithelium healed, and inflammation and interface edema resolved. At 10 years of follow-up, the patient had developed a localized pseudopterygium with mild corneal neovascularization but maintained 20/20 uncorrected visual acuity., Conclusions: A chemical burn over a LASIK flap poses a challenge for managing corticosteroids, which are required to prevent diffuse lamellar keratitis but can also contribute to keratolysis beyond the first week after an alkali injury. Oral corticosteroid therapy may be beneficial in this situation, with a low threshold to lift the LASIK flap and debride the interface if inflammation occurs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To describe progressive corneal microcyst-like epithelial changes (MECs) that developed in patients treated with the investigational drug belantamab mafodotin (belamaf) for refractory multiple myeloma (MM)., Methods: This is a single center case series of patients with MM receiving the investigational drug belamaf., Results: All 12 patients included in this analysis who were treated with belamaf developed MECs that initially appeared in the peripheral cornea and progressed centrally with time. Cessation of therapy resulted in regression of the MECs first in the periphery then centrally. Microcyst-like epithelial changes recurred in all patients on retreatment. With prolonged therapy, eight patients developed corneal staining patterns suggestive of limbal stem cell dysfunction (LSCD)., Conclusion: We describe MECs and LSCD associated with systemic administration of belamaf. Further study is needed to determine the etiology and composition of the MECs and the mechanism of limbal stem cell involvement., Competing Interests: B.H. Jeng is a consultant for GlaxoSmithKline. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Contact Lens Association of Ophthalmologists.)

Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of glycosaminoglycans (GAGs) and PGs after a chemical injury. The chemical composition of chondroitin sulfate (CS)/dermatan sulfate (DS) and heparan sulfate (HS) were characterized in mouse corneas 5 and 14 days after alkali burn (AB), and compared to uninjured corneas. The expression profile and corneal distribution of CS/DSPGs and keratan sulfate (KS) PGs were also analyzed. We found a significant overall increase in CS after AB, with an increase in sulfated forms of CS and a decrease in lesser sulfated forms of CS. Expression of the CSPGs biglycan and versican was increased after AB, while decorin expression was decreased. We also found an increase in KS expression 14 days after AB, with an increase in lumican and mimecan expression, and a decrease in keratocan expression. No significant changes in HS composition were noted after AB. Taken together, our study reveals significant changes in the composition of the extracellular matrix following a corneal chemical injury.

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.

Background/aim: To describe the clinical progress and management of ocular side effects in a 35-year-old patient with metastatic breast cancer who underwent oral chemotherapy with capecitabine and lapatinib., Materials and Methods: Slit lamp evaluation revealed bilateral perikeratic hyperemia, perilimbal conjunctival edema associated with corneal marginal infiltrates and epithelial and anterior stromal defects in both eyes. Slit lamp examination, in vivo confocal microscopy and anterior-segment optical coherence tomography were highly suggestive for limbal stem cell deficiency. The decision to administer autologous blood- derived serum eye drops was made., Results: Following administration of autologous blood-derived serum eye drops, corneal marginal infiltrates, epithelial and stromal defects significantly regressed in both eyes after only 10 days. Chemotherapy was resumed and serum eye drops were prescribed simultaneously., Conclusion: Autologous blood-derived serum eye drops may be an adequate therapeutic choice for bilateral corneal lesions detected as ocular side effects of capecitabine., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We report two patients who developed toxic keratopathy following high-dose cytarabine chemotherapy and whose symptoms resolved following topical loteprednol etabonate 0.5% treatment. A 25-year-old woman and a 26-year-old man with acute myeloid leukemia were referred to our department with symptoms of ocular discomfort, photophobia, and blurred vision after consolidation chemotherapy. Central corneal epithelial microcysts were observed bilaterally in both patients, and in vivo confocal microscopy showed highly reflective disseminated granular and irregular intraepithelial opacities, mainly in the basal epithelial layers. Loteprednol etabonate 0.5% relieved both patients' symptoms in less than a week, and the microcysts disappeared in 2 to 3 weeks of treatment. Although there is no standardized treatment protocol for cytarabine-induced corneal toxicity, dexamethasone 0.1% and prednisolone phosphate 1.0% were reported to be effective in the resolution of discomfort and symptoms. In the two patients we report herein, loteprednol etabonate 0.5% four times daily was also effective in suppressing the symptoms.

Purpose: The aim of this study was to examine the effects of long-term use of hydroxychloroquine (HQ) on the pachymetric, aberrometric, and densitometric values of the cornea and corneal endothelium in lupus patients., Method: Twenty-two eyes (study group) of 22 patients using HQ for treatment of lupus and 25 eyes (control group) of 25 healthy individuals were included in this prospective study. A specular microscopy was used to measure corneal endothelial cell density (ECD), percentage of hexagonal cells (HEX%), coefficient of variation of the cell size (CV). Then, a Pentacam® HR corneal tomography system was used to measure central corneal thickness (CCT), corneal aberrometry values in 6-mm pupil diameters and corneal densitometry values in 6-mm corneal zones (0-2 mm and 2-6 mm)., Results: While ECD was significantly lower in the study group than in the control group ( p  = 0.034), CCT was significantly higher in the study group ( p  = 0.032). The higher-order aberrations values and the anterior corneal densitometry values in the 0-2 mm and 2-6 mm corneal zones in the study group were found to be significantly higher than the control group ( p  = 0.021, p  = 0.007 and p  = 0.013)., Conclusion: Prolonged use of HQ may cause some changes in the cornea. In the follow-up of these cases, detailed examination of the cornea as well as the macula may be important for the protection of corneal health.

Our purpose is to document the first case of unilateral mild corneal ectasia developed in an apparently nonpredisposed cornea after topical latanoprost treatment, and its regression after treatment withdrawal. We describe a 44-year-old man with visual impairment in his left eye (OS) and a past medical history of myopic refraction and ocular hypertension with latanoprost treatment, the rest of ocular examination was normal. A decrease in visual acuity was observed with a refractive change. Corneal tomography showed features of mild corneal ectasia in his OS. Topical prostaglandin analogue therapy was removed and replaced by other antiglaucoma topical treatment. Corneal tomography returned to normal, an improvement in the quality of vision was observed and refractive astigmatism recovered to baseline values. This case illustrates that topical latanoprost does affect the matrix metalloproteinases balance in corneal extracellular matrix, and subsequently may produce a corneal weakening. Corneal biomechanical features and corneal stiffness do probably recover after topical prostaglandin analogues withdrawal.

Background: Paclitaxel (PTX) is an antineoplastic drug widely used in treatments for ovarian, breast, and small-cell lung cancer. Although ocular effects associated with PTX have been previously described, very few studies have specifically reported systemic PTX as a contributing factor for limbal stem cell deficiency (LSCD), which is characterized by the loss of stem cell and barrier function of the limbus leading to progressive pain and reduction in visual acuity. Described here is a unique case where a patient was diagnosed with LSCD secondary to PTX use for the treatment of breast cancer, at doses of PTX far lower than what is reported in current literature., Case Presentation: A 73-year-old woman with a previous diagnosis of breast cancer with liver metastasis presented with a complaint of increasing pain in the left eye more than the right, along with decreasing visual acuity in both eyes following 3 months of PTX therapy for recurrent liver metastases. Upon examination, best-corrected visual acuity was 20/100 in the right eye and counting fingers on the left. Peripheral neovascularization, stromal scarring, and features of limbal stem cell deficiency (LSCD) were noted on the right cornea. A central neurotrophic ulcer with thinning to 50% and 360 degrees of conjunctivalization were noted on the left. After the discontinuation PTX with doxorubicin as the substitute, there was no further progression of her LSCD, and stabilization of her ocular surface was achieved., Conclusion: Although chemotherapy induced LSCD is a relatively rare adverse event, it is essential for clinicians starting new chemotherapy agents to consider the potential ocular toxicities that may result in their use. Ophthalmology review is recommended for patients after starting PTX therapy to assess for signs of LSCD, particularly in patients where drug toxicity can be aggravated due to impaired hepatic function.

Significance: Amiodarone is an excellent antiarrhythmic medication; however, it has numerous systemic and ocular adverse effects., Purpose: We aimed to improve our understanding of amiodarone and its ocular adverse effects by performing a systematic review and meta-analysis of published case reports., Methods: This systematic review was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We used the MEDLINE database, primarily through PubMed, and used keywords (amiodarone, eye, eye diseases, visual/ocular adverse effects/manifestations) to identify case reports of ocular adverse effects after amiodarone use. The initial search resulted in 92 total case reports. However, after excluding nonrelevant case reports, 25 cases were selected for the final analysis., Results: Among the patients in the 25 case reports, 18 were male (72%), and the median age was 66 ± 9.9 years. In 15 cases (60%), the patients reported halos around light and/or decrease in vision after amiodarone use. The most common ophthalmic examination findings were cornea verticillata/vortex keratopathy in 19 cases (76%), followed by different patterns of papilledema and retinal hemorrhages in 5 cases (20%). Discontinuation of amiodarone was the most common intervention, followed by application of topical heparin. Outcomes among case reports were variable., Conclusions: Cornea verticillata/vortex keratopathy was the most common ocular adverse effect in cases where amiodarone was administered. Early recognition of amiodarone-induced ocular adverse effects is imperative to prevent worsening keratopathy or uncommon adverse effects. Collaboration between physicians prescribing amiodarone-to recognize the ocular symptoms-and referral to eye care physicians are important.

Purpose: To report a case of reversible corneal endothelial abnormalities after treatment with netarsudil., Observation: A 68-year-old woman presented with the complaint of blurred vision soon after starting treatment with the fixed-dose combination of netarsudil and latanoprost (FC-netarsudil-latanoprost). She had been receiving the fixed-dose combination of dorzolamide and timolol and latanoprost for primary open-angle glaucoma until her ophthalmologist switched latanoprost to FC-netarsudil-latanoprost 2 months before referral to our center.Best-corrected visual acuity was 20/20-1 in the right eye and 20/20-3 in the left eye. The slit-lamp biomicroscopic examination was remarkable for a guttata-like abnormality of the corneal endothelium of both eyes. The intraocular pressure was 10 mm Hg in both eyes. Specular microscopy revealed irregularly shaped corneal endothelial cells with indistinct borders between cells. FC-netarsudil-latanoprost was replaced with latanoprost in the left eye but continued in the right eye. Nine weeks later, best-corrected visual acuity remained 20/20-1 in the right eye but it improved to 20/20 in the left eye. Repeat specular microscopy was unchanged in the right eye and was normal in the left eye., Conclusion and Importance: Topical therapy with netarsudil can result in guttata-like changes of the corneal endothelium and corneal endothelial cell abnormalities that can be detected with specular microscopy. These abnormalities seem to be transient and resolved upon the cessation of netarsudil. Ophthalmologists should consider the possibility of a corneal endothelial abnormality in patients treated with netarsudil who develop blurred vision.

Rationale: Rifabutin is a broad-spectrum antibiotic known to cause deposits on the corneal endothelium and lens. We report a patient in whom cataracts developed and progressive pigment deposits were seen on the corneal endothelium, lens, and iridocorneal angle., Patient Concerns: The patient was a 45-year-old woman who had been received long-term treatment with a combination of various anti-mycobacterial drugs for multidrug-resistant tuberculosis starting in 2004. Rifabutin was started in 2009, and she was referred to our department in 2017 for detailed ophthalmological examination., Diagnoses: Both eyes showed pigmented deposits over the entire corneal endothelium, the entire periphery of the iridocorneal angle, and the anterior surface of the lens. Mild cataracts were also diagnosed bilaterally. Pigment deposits on the anterior surface of the lens and the cataracts in both eyes gradually progressed. These lesions were assumed to be associated with long term rifabutin intake., Interventions: Rifabutin intake was discontinued after progression of intraocular deposits, cataracts, and ERG deterioration., Outcomes: Visual acuity improved, although cataracts, deposits, and ERG deterioration remained., Lessons: Rifabutin may induce not only corneal endothelial deposits, but also cataracts and iridocorneal angle deposits.

Purpose: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water., Methods: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5)., Results: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) ( p  = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining ( p  < 0.0001), Ocular Surface Disease Index ( p  < 0.05), and visual analog scale ( p  = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent., Conclusion: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL ® , has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.

Competing Interests: None

Purpose: To investigate the effects of topical autologous serum application on the ocular surface in patients with toxic corneal epitheliopathy induced by anti-glaucoma drugs., Methods: The patients who had corneal epitheliopathy because of preservative-containing anti-glaucoma eye drops were prospectively enrolled. The epitheliopathy was refractory to preservative-free artificial tear treatment. The patients topically applied 20% autologous serum to the eye eight times per day for 1 month. Baseline and one-month change in symptoms and signs were assessed by the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (TFBUT), Schirmer I values, corneoconjunctival staining scores, corneal sensitivity, InflammaDry ® tear immunoassay, and tear cytokine profiles using a bead-based multiplex assay., Results: A total of ten consecutive patients were enrolled between January and August 2018 and evaluated after one-month treatment with 20% autologous serum eye drops. Significant improvement was observed in symptoms (OSDI scores from 25.5 ± 20.9 to 10.5 ± 12.0; P = .039), TFBUT (from 3.1 ± 1.8 s to 5.4 ± 2.3 s; P = .025), corneoconjunctival staining scores (from 7.7 ± 1.8 to 1.8 ± 1.9 NEI scale; P = .005), corneal sensitivity (from 4.6 ± .9 cm to 5.8 ± .5 cm; P = .013), and metalloproteinase-9 levels (P = .013). There were no significant changes in Schirmer I values and tear cytokine levels on multiplex assays. Treatment-related side effects were not detected., Conclusions: Topical instillation of 20% autologous serum is an effective treatment for toxic corneal epitheliopathy associated with anti-glaucoma eye drops., Trial Registration Number: KCT0003827.