Presumed erlotinib-induced bilateral corneal ulcers in a dog with lung tumor.

OBJECTIVE: To report the corneal toxicity of erlotinib in dogs. ANIMAL STUDIED: A 13-year-old castrated male Maltese dog. RESULTS: A dog with lung cancer presented with a month-long history of mucoid discharge and blepharospasm in both eyes. Corneal ulcerations with stromal thinning were diagnosed in both eyes, which were refractory after 2 weeks of treatment with topical antibiotics and artificial tears. The dog was orally administered erlotinib (Tarceva®) by his owner for 2 months to treat his lung cancer. Urgent withholding of erlotinib was recommended, and after 2 weeks of discontinuation, the corneal defects resolved; however, corneal thinning remained until the six-month follow-up. CONCLUSIONS: To the best of author's knowledge, this is the first report in the veterinary literature that describes bilateral corneal ulcers associated with erlotinib administration in a dog.

Allogenic platelet-rich plasma in induced ulcers in rat's cornea / [Plasma rico em plaquetas alogênico em úlceras de córnea induzidas em ratos]

The objective in this study was to evaluate the clinic effect of applying allogenic platelet-rich plasma (PRP) heated or not, for treating cornea ulcers, including the dosage of PDGF-BB in the cornea. The ulcers were induced, standardizing the left eye from 81 rats (Ratus norvegicus, albinus variety), assigned randomly into three groups (N=27): control group (CG) which did not receive any topic treatment; heated PRP group (GA) and PRP group (GP), which received topical treatment every eight hours for five days. Each group underwent evaluation at 24 hours (M1), three days (M3) and five days (M5). The clinical exam evaluated the opacity, vascularization and corneal repair. The corneal PDGF-BB was dosed through the ELISA method. The corneal opacity was decreased in PRP-treated animals (GA and GP) and corneal repair time reduced when compared to CG at M1 and M5. Furthermore, GP showed greater vascularization at M3 compared to M1. Applied allogenic PRP eye drops, heated or not, speed up corneal healing, and reduce corneal repair time. However, the corneal PDGF concentration was not altered in any of the treatments.(AU)

Objetivou-se avaliar o efeito clínico da aplicação de plasma rico em plaquetas alogênico (PRP) aquecido ou não, no tratamento de úlceras de córnea, como a dosagem de PDGF-BB na córnea. As úlceras foram induzidas, padronizando-se o olho esquerdo de 81 ratos (Rattus norvegicus, variedade albinus), aleatoriamente, nos três grupos (N = 27): grupo controle (CG), que não recebeu nenhum tratamento tópico; grupo PRP aquecido (GA) e grupo PRP (GP), que receberam tratamento tópico a cada oito horas, durante cinco dias. Cada grupo foi subdividido em 24 horas (M1), três dias (M3) e cinco dias (M5). O exame clínico avaliou a opacidade, a vascularização e o reparo corneano. O PDGF-BB corneano foi dosado pelo método Elisa. Houve diminuição da opacidade da córnea nos animais tratados com PRP (GA e GP) e diminuição do tempo de reparo da córnea em comparação com CG, M1 e M5. Além disso, foi observada maior vascularização no GP no momento M3 em relação ao M1. A aplicação de colírios de PRP alogênico, aquecidos ou não, acelera a cicatrização da córnea, além de reduzir o tempo de reparo da córnea. No entanto, a concentração de PDGF na córnea não se alterou em nenhum dos tratamentos.(AU)

Bilateral Corneal Perforation in a Patient Under Anti-PD1 Therapy.

ABSTRACT: Immune checkpoint inhibition has improved the clinical outcomes for numerous patients with cancer. However, the downside is a whole new spectrum of immune-related adverse events. We report a 68-year-old man with a history of nonsmall cell lung cancer presenting with a spontaneous corneal perforation in the right eye after 22 cycles of pembrolizumab. In addition, a chronic central nonhealing epithelial defect developed after performing a penetrating keratoplasty. Treatment with autologous serum drops resulted in complete healing of the corneal ulcer, where other conventional therapies had no effect. One month after reinitiating pembrolizumab therapy, our patient presented again with a corneal perforation in the fellow eye. This case describes relapsing sterile ulcerations associated with pembrolizumab use and presents an unexpected cure.

Nivolumab-Induced Ulcerative Keratitis-A Case Report.

PURPOSE: To describe a case of nivolumab-induced ulcerative keratitis rapidly recovering on topical steroid treatment and to determine changes in cytokine levels in the tear fluid caused by nivolumab. METHODS: We report a 34-year-old man receiving nivolumab for metastasized melanoma with severe dry eye symptoms and a persistent corneal epithelial defect. Levels of cytokine and matrix metalloproteinase in tear fluid were measured by multiplex immunoassays. RESULTS: The corneal epithelial defect failed to recover for antiviral and lubrication therapy but resolved within 48 hours after topical steroid therapy was initiated. No recurrence of corneal ulceration was observed with intermittent topical steroid therapy during the remaining period of nivolumab treatment. No Sjögren disease-related autoantibodies were detected in the patient's serum. The levels of inflammatory cytokines and matrix metalloproteinases in the tear fluid were markedly elevated after nivolumab treatment. CONCLUSIONS: Our observations suggest that nivolumab treatment induces a local autoimmune ocular surface disorder resulting in corneal ulceration that promptly resolves using steroid eye drops. The integrity of the corneal epithelial layer can be sustained using intermittent topical steroid therapy in patients receiving nivolumab.

Crown Ether Nanovesicles (Crownsomes) Repositioned Phenytoin for Healing of Corneal Ulcers.

Drug repositioning is an important drug development strategy as it saves the time and efforts exerted in drug discovery. Since reepithelization of the cornea is a critical problem, we envisioned that the anticonvulsant phenytoin sodium can promote reepithelization of corneal ulcers as it was repurposed for skin wound healing. Herein, our aim is to develop novel crown ether-based nanovesicles "Crownsomes" of phenytoin sodium for ocular delivery with minimal drug-induced irritation and enhanced efficacy owing to "host-guest" properties of crown ethers. Crownsomes were successfully fabricated using span-60 and 18-crown-6 and their size, morphology, polydispersity index, ζ potential, drug loading efficiency, conductivity, and drug release were characterized. Crownsomes exhibited favorable properties such as formation of spherical nanovesicles of 280 ± 18 nm and -26.10 ± 1.21 mV surface charges. Crownsomes depicted a high entrapment efficiency (77 ± 5%) with enhanced and controlled-release pattern of phenytoin sodium. The optimum crownsomes formulation ameliorated ex vivo corneal drug permeability (1.78-fold than drug suspension) through the corneal calcium extraction ability of 18-crown-6. In vivo study was conducted utilizing an alkali-induced corneal injury rabbit model. Clinical and histopathological examination confirmed that crownsomes exhibited better biocompatibility and minimal irritation due to complex formation and drug shielding. Further, they enhanced corneal healing, indicating their effectiveness as a novel drug delivery system for ocular diseases.

Late-Onset Sterile Peripheral Ulcerative Keratitis Post-Corneal Collagen Crosslinking.

PURPOSE: To report the incidence, characteristics, clinical presentations, risk factors, and the available treatment modalities of sterile peripheral ulcerative keratitis (PUK) post-corneal collagen crosslinking (CXL). METHODS: This study is a retrospective study including 771 eyes of 474 patients operated for keratoconus or ectasia after LASIK between January 2010 and June 2017 at Beirut Eye & ENT Specialist hospital. The average follow-up period was 4.2 years with a minimum of 1 year post-CXL. RESULTS: Eleven eyes (1.4%) of 8 patients developed late-onset PUK with or without corneal haze and sterile infiltrates. The complications occurred between 3 months and 6 years postoperatively. Their mean age of 39.6 ± 7.1 years was higher than the age of the noncomplicated patients 21.9 ± 8.8 years (P = 0.0001). Four affected patients had inflammatory and autoimmune conditions. Sex, presence of intrastromal ring segments, mean keratometry, and the thinnest pachymetry were found to be insignificantly different between groups, and photorefractive keratectomy was performed more in patients with keratitis. Duration of ultraviolet light exposure was related to sterile ulcerative keratitis development. All patients responded to steroid treatment, and only one had a relapse which resolved with topical cyclosporine 1% drops. CONCLUSIONS: PUK is a rare but serious complication after CXL. Long-term follow-up is necessary to detect late-onset PUK. It is a treatable condition associated with older age and autoimmune conditions but has a good visual outcome.

Bilateral Ulcerative Keratitis Associated With Afatinib Treatment for Non-Small-cell Lung Carcinoma.

PURPOSE: To report a case of afatinib-related bilateral ulcerative keratitis. METHODS: An 85-year-old female patient on treatment with afatinib for non-small-cell lung carcinoma presented with progressive redness, pain, and decreased vision in both eyes. Four weeks before the onset of symptoms, afatinib therapy had been commenced at a dose of 40 mg, once daily. Clinical examination, OCT imaging, photographs, and corneal scrapes were completed at presentation. Afatinib was discontinued. Topical and oral therapy were commenced to treat ulcerative keratitis with close monitoring for signs of progression or corneal perforation. RESULTS: Significant stromal thinning was detected in the inferior cornea of both eyes with an overlying epithelial defect and no infiltrate. No organisms were identified from the corneal scrapes. The patient responded well to treatment, and her vision returned to baseline 4 months after presentation. CONCLUSIONS: To the best of our knowledge, this is the first case in the literature that reports afatinib-related ulcerative keratitis. Careful monitoring for signs of ocular adverse events is recommended during treatment with afatinib for non-small-cell lung carcinoma.

Plasma rich in growth factors for the treatment of rapidly progressing refractory corneal melting due to erlotinib in nonsmall cell lung cancer.

RATIONALE: Erlotinib, an antineoplastic agent, is indicated for the treatment of patients with advanced nonsmall cell lung cancer. Most common adverse events are manageable, although more severe ones require dose reduction or discontinuation of erlotinib treatment. PATIENT CONCERNS: We present a case of severe corneal ulcer treated with autologous plasma rich in growth factors. DIAGNOSES: A 76-year-old woman with stage IVB (cT2a N0 M1c) lung cancer under erlotinib treatment presented with rapidly progressing corneal ulcer. Evolution was torpid and refractory to conventional treatment. INTERVENTIONS: Surgical options were dismissed because of the poor performance status of the patient. Despite temporary discontinuation of erlotinib treatment, the corneal ulcer continued to worsen with peripheral corneal neovascularization, stromal thinning, corneal edema, and profuse inflammation of the ocular surface. OUTCOMES: Treatment with autologous plasma rich in growth factors prevented an imminent corneal perforation and improved the corneal ulcer for over a year of follow-up. LESSONS: Considering the poor results of conventional treatment, both medical and surgical, management of the inflammation of the ocular surface together with the stimulation of the healing processes through regenerative therapy such as PRGF, can be an option worth considering in these cases.

Ulcerative keratitis in patients with rheumatoid arthritis in the modern biologic era: a series of eight cases and literature review.

AIM: To assess the prevalence, clinical characteristics, treatment, and outcomes of patients who developed ulcerative keratitis (UK) during the course of rheumatoid arthritis (RA) in the modern biologic era. METHOD: We retrospectively reviewed the medical records of 589 patients with RA who visited our department between April 2003 and October 2014, and identified patients who developed UK. We also obtained data about clinical characteristics of RA and UK, complications, treatment, and both visual and life prognoses of these patients. RESULTS: Among 589 patients with RA, eight patients (1.4%) were diagnosed with UK. The mean age at the onset of RA was 61.0 years, while the mean age at the onset of UK was 73.0 years. Most of the patients were seropositive and had established RA with a relatively low disease activity. Secondary Sjögren's syndrome was observed in two patients. Peripheral UK occurred as a complication of scleritis, while central UK was not associated with scleritis. Although the mean duration of follow-up was only 3.7 years, visual and life prognoses were both tolerable with therapy, including the use of topical and systemic corticosteroids and calcineurin inhibitors, sometimes combined with biologic disease-modifying antirheumatic drugs (DMARDs) and corneal transplantation. CONCLUSION: This retrospective study demonstrated that the prevalence of UK in patients with RA was 1.4%. Immediate combination therapy, including topical and systemic corticosteroids and calcineurin inhibitors, together with biologic DMARDs and corneal transplantation, was effective for treating RA patients who developed UK in the modern biologic era.

Acquired anterior staphyloma after corneal ulcer associated with the use of crack.

We describe an unusual case of acquired anterior staphyloma in a patient addicted to crack cocaine. At the beginning of his crack cocaine abuse, he noticed redness and irritation of his eyes. Over the next 4 months, the patient also noticed the onset of decreasing visual acuity in his right eye (OD). Initially, his visual acuity was light perception in OD, and slit-lamp examination revealed a corneal infiltrate with a peripheral perforation and an iris prolapse. The patient was hospitalized to ensure compliance with the prescribed treatment and was advised to undergo therapeutic keratoplasty; however, the patient left the hospital against medical advice and was lost to follow-up for the next 6 months. He returned with complaints of photophobia and the inability to close his right eyelids. At this time, his cornea had developed an anterior staphyloma and required a sclerokeratoplasty. Following surgery, the patient was again lost to follow-up.

Acquired anterior staphyloma after corneal ulcer associated with the use of crack / Estafiloma anterior adquirido após úlcera de córnea associado a uso de crack

ABSTRACT We describe an unusual case of acquired anterior staphyloma in a patient addicted to crack cocaine. At the beginning of his crack cocaine abuse, he noticed redness and irritation of his eyes. Over the next 4 months, the patient also noticed the onset of decreasing visual acuity in his right eye (OD). Initially, his visual acuity was light perception in OD, and slit-lamp examination revealed a corneal infiltrate with a peripheral perforation and an iris prolapse. The patient was hospitalized to ensure compliance with the prescribed treatment and was advised to undergo therapeutic keratoplasty; however, the patient left the hospital against medical advice and was lost to follow-up for the next 6 months. He returned with complaints of photophobia and the inability to close his right eyelids. At this time, his cornea had developed an anterior staphyloma and required a sclerokeratoplasty. Following surgery, the patient was again lost to follow-up.

RESUMO Descrevemos um raro caso de estafiloma anterior adquirido em um paciente viciado em crack. No início do uso do crack, paciente observou hiperemia e irritação nos seus olhos. Durante os próximos 4 meses, evoluiu com piora progressiva da visão em seu olho direito (OD). Inicialmente, sua visão no OD era de percepção luminosa e ao exame de biomicroscopia observava-se um importante infiltrado corneano com uma perfuração periférica e hérnia de íris. O paciente foi hospitalizado para garantir seu correto tratamento e indicado ceratoplastia terapêutica; no entanto, o paciente abandou o hospital e ficou 6 meses sem acompanhamento. Após esse período, paciente retornou queixando-se de importante fotofobia e inabilidade em ocluir o OD. Neste momento, sua córnea havia desenvolvido um importante estafiloma anterior e necessitou de uma escleroceratoplastia no OD. Após a cirurgia, mais uma vez o paciente abandonou o tratamento e perdeu o seguimento pós-operatório.

Ipilimumab-induced Ocular and Orbital Inflammation--A Case Series and Review of the Literature.

PURPOSE: Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called "immune-related adverse events" (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy. METHODS: We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions. RESULTS: Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy. CONCLUSIONS: Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae.

Trastuzumab-induced corneal ulceration: successful no-drug treatment of a "blind" side effect in a case report.

BACKGROUND: We report the first successful treatment of limbal lesions and corneal erosion experienced by a breast cancer patient undergoing trastuzumab treatment. CASE PRESENTATION: A 49-year-old Caucasian woman with early stage breast cancer was treated with adjuvant trastuzumab and subsequently showed persistent bilateral corneal marginal infiltrates resistant to topical steroid and antibiotic treatment. Autologous serum was applied in the conjunctival sac as an experimental treatment to antagonize the inhibitory effect of the HER2 receptor antibody on the corneal epithelial cells. Topical application of autologous serum led to rapid improvement of the ulcerative keratitis, with complete healing of the corneal defect after 7 days. Continued administration of the serum allowed the resumption of trastuzumab therapy without any further side effects. CONCLUSIONS: Persistent bilateral corneal marginal infiltrates may occasionally arise as a side effect of trastuzumab treatment. Topical medication with autologous serum may be an effective therapeutic option for the ocular side effects of trastuzumab therapy.

Avaliação histomorfométrica e da proliferação celular em úlceras de córnea superficiais, induzidas em coelhos, após o uso de colírio de Citrus lemon / Histomorphometry evaluation and cellular proliferation in superficial corneal ulcer, induced in rabbits, after using eyedrops of Citrus lemon

O objetivo do presente estudo foi avaliar e comparar, por meio de histomorfometria e imuno-histoquímica para PCNA (Antígeno Nuclear de Proliferação Celular), o processo de reparação corneal de úlceras superficiais induzidas em coelhos e tratadas com colírios de óleo essencial de Citrus lemon (CL). Foram utilizadas 40 fêmeas da espécie leporina, constituindo-se quatro grupos experimentais de 10 animais cada. Todos os animais foram submetidos à indução da úlcera superficial experimental por meio da aplicação tópica de n-heptanol. Em dois grupos foram instilados colírios à base de óleo essencial de Citrus lemon, em diferentes concentrações, sendo 3% (GL3) e 5% (GL5). Outro grupo foi tratado com Tween 80 8% (GT), que é o diluente utilizado na produção dos colírios de CL; o grupo controle (GC) recebeu apenas substituto da lágrima. Todos os colírios foram aplicados quatro vezes ao dia. Os grupos experimentais foram distribuídos em dois subgrupos, com cinco animais cada, de acordo com os períodos finais de avaliação. O primeiro subgrupo (M1) foi avaliado após 24 horas e o segundo (M2), após cinco dias. Nas comparações entre os momentos iniciais e finais, os grupos tratados com substituto da lágrima, Tween 80 8% e colírio à base de óleo essencial de Citrus lemon 5% promoveram aumento na espessura epitelial na periferia da córnea e maior percentual de proliferação celular. Não houve diferença de celularidade entre os tratamentos. Os colírios à base de óleo essencial de Citrus lemon, nas diferentes concentrações, promoveram a reepitelização corneal, sem causar lesões adicionais ao epitélio ou estroma corneal, podendo ser utilizado na superfície ocular.

The aim of this study was to evaluate and compare through histomorphometry and immunohistochemistry for PCNA (Proliferating Cell Nuclear Antigen), the repair process in superficial corneal ulcers induced in rabbits and treated with eyedrops of Citrus lemon (CL) essential oil. Fifty female rabbits were used and divided into 4 experimental groups of 10 animals each one. Every animal underwent induction of experimental superficial ulcer by topical application of n-heptanol. Three groups were treated with eyedrops of Citrus lemon essential oil in two different concentrations: 3% (GL3) and 5% (GL5). Another group was treated with Tween 80 8% (GT), which is the solvent used in the production of eyedrops of CL; the control group (CG) received only tear substitute. All eyedrops were applied four times daily. The experimental groups were divided into two subgroups with five animals in each one, according to the final evaluation periods. The first subgroup (M1) was evaluated after 24 hours and the second (M2) after 5 days. In the comparison between the initial and final moments, the groups treated with tear substitute, Tween 80 8% and eyedrops of Citrus lemon essential oil 5% had an increase in epithelial thickness at the periphery of the cornea and a higher percentage of cell proliferation. There was no difference in cellularity between treatments. The eyedrops of Citrus lemon essential oil, at different concentrations, promoted corneal reepithelialization without causing further injury to the epithelium and corneal stroma, so they can be used on the ocular surface.

A case of nicorandil-induced unilateral corneal ulceration.

Nicorandil, a second-generation nitro derivative, has been reported to induce single or multiple ulcerations in many locations, including oral, anal, perianal, vulvovaginal, perivulval, penile, gastrointestinal, colic, peristomal and skin locations. Ocular locations are now highly suspected. Herein, we report the case of a 78-year-old woman who experienced corneal ulceration at second cataract surgery (right eye) while being treated with nicorandil for 3 years. Four years before, she had had an uneventful first cataract surgery (left eye). The ulcers healed within 6 weeks after simple withdrawal of nicorandil, an expected delay for this type of chemical ulcer. The substitution of nicorandil with classic nitric oxide donors has already been done without complication. Surgical intervention is unnecessary and inappropriate. Case reports of ocular side effects induced by nicorandil are rare and probably underestimated.

A rat model of autologous oral mucosal epithelial transplantation for corneal limbal stem cell failure.

PURPOSE: To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency. METHODS: The study was carried from August to October 2012. Fourteen SD rats were randomly and evenly allocated to study group A and control group B. Limbal stem cell deficiency was established by alkali burn in the right eye of each rat in both groups. Rats in group A received autologous oral mucosa strip transplantation following the chemical burn. Rats in group B did not receive surgery after the chemical burn. Topical antibiotics and dexamethasone were used in all rats. Corneal clarity, corneal fluorescein staining, oral mucosal graft survival, and complications at postoperative days 1, 3, 7, 14 were observed. RESULTS: The oral mucosa strip graft was detached in one rat in group A. Reepithelialization was observed starting from the graft position and was completed within 14 days in the remaining 6 eyes in group A. However, persistent corneal epithelium defect was observed in all eyes in group B, among which corneal melting and perforation was observed in 2 eyes and corneal opacification with neovascularization was observed in the remaining 5 eyes. CONCLUSION: Autologous oral mucosa strip grafting for limbal stem cell deficiency can be achieved by a rat model following chemical burn. The fate of the transplanted oral mucosal epithelial cells warrants further study.