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Objective: To investigate the association between exposure to topical ophthalmic antibiotics during pregnancy and adverse neonatal outcomes., Methods: In this retrospective cohort study, we identified pregnant women with hordeola, chalazia, blepharitis, or bacterial conjunctivitis from 2005 to 2018 using the Japanese Medical Data Centre Claims Database. From the eligible women, we extracted women who were dispensed no topical antibiotics during the first trimester (non-antibiotic group), women who were dispensed topical fluoroquinolones alone at least once (fluoroquinolone alone group), and women who were dispensed any single type of antibiotic (single-antibiotic group). We compared the frequency of congenital anomalies (CA), preterm birth (PB), low birth weight (LBW), and the composite outcome of these three between the fluoroquinolone and non-antibiotic groups and between the single-antibiotic and non-antibiotic groups, using propensity score adjustment., Results: A total of 891 eligible women were identified. In the fluoroquinolone (n = 409) and non-antibiotic (n = 309) groups, CA occurred in 6.8% and 6.8%, PB in 2.4% and 3.2%, LBW in 2.9% and 3.2%, and the composite outcome in 10.5% and 11.3%, respectively. Analysis using propensity score adjustment showed no significant difference between the groups in the frequency of CA (adjusted odds ratio, 1.15; 95% confidence interval, 0.61-2.18), PB (0.80; 0.30-2.17), LBW (1.08; 0.45-2.63), or the composite outcome (1.12; 0.67-1.87). Comparison of the single-antibiotic and non-antibiotic groups showed similar results., Conclusions: Topical ophthalmic antibiotics for hordeola, chalazia, blepharitis, or bacterial conjunctivitis during the first trimester were not associated with increased adverse neonatal outcomes., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: Glaucoma is a leading cause of irreversible blindness and ripasudil was the first Rho kinase inhibitor approved as antiglaucoma medication. Here we present the final analysis of the ROCK-J study, a large-scale post-marketing surveillance study to evaluate the long-term safety and effectiveness of ripasudil in Japanese patients with glaucoma or ocular hypertension in a real-word clinical setting., Methods: ROCK-J was a 24-month, prospective, open-label, observational study that included ripasudil-naïve patients with glaucoma or ocular hypertension who were initiating treatment with ripasudil according to the Japanese approved indication between June 1, 2015 and April 30, 2017. The primary safety endpoint was the incidence of adverse drug reactions (ADRs) (including blepharitis, plus assessment of its background factors); the primary efficacy endpoint was change in intraocular pressure (IOP) from baseline to 24 months., Results: A total of 3374 Japanese patients with glaucoma or ocular hypertension were evaluated for safety and 3178 for effectiveness of ripasudil over a mean 524.5-day observational period. Overall, 853 (25.3%) patients experienced adverse drug reactions; the most common were blepharitis (8.6%), conjunctival hyperemia (8.5%), and conjunctivitis (6.3%). Multivariate analyses demonstrated that patients were more likely to experience the ADR blepharitis with ripasudil treatment if they were female (hazard ratio [HR] 1.307; p = 0.040), had comorbid or a previous history of blepharitis (HR 2.178; p = 0.001), or had a history of allergy to pollen (HR 1.645; p = 0.003) or medication (HR 2.276; p < 0.001). IOP decreased significantly from baseline with ripasudil; the least-squares mean ± standard error change in IOP from baseline to 24 months was - 2.6 ± 0.1 mmHg (p < 0.001). Significant IOP changes were seen in four types of glaucoma, namely primary open-angle glaucoma, normal-tension glaucoma, primary angle-closure glaucoma, and secondary glaucoma, and ocular hypertension., Conclusion: Ripasudil was safe and effective as an antiglaucoma medication with no new safety signals identified and significant reductions in IOP maintained over 24 months of treatment., (© 2022. The Author(s).)

Background: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and has aesthetic, physical, and emotional-social sequelae when left untreated., Objective: To classify the most common adverse reactions associated with dupilumab treatment in patients with AD., Methods: The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions associated with dupilumab, topical pimecrolimus, and topical tacrolimus. Phase III clinical trial data were used to compare the rate of herpes infections between the treatment group and placebo group., Results: The most common adverse reaction associated with dupilumab was ocular complications. Herpes infections were extremely rare in the patients with AD being treated with dupilumab., Limitations: Prescribing information for dupilumab, topical pimecrolimus, and topical tacrolimus is not available. Adverse effects are reported by patients, health care providers, and pharmaceutical companies, they have not been corroborated., Conclusions: Ocular complications are the most common complication associated with dupilumab. The rate of herpes infection is low in patients being treated with dupilumab, topical pimecrolimus, and topical tacrolimus. There is no significant difference for the rate of herpes infection between, placebo, dupilumab, topical pimecrolimus, and the topical tacrolimus treatment group, suggesting that dupilumab does not affect herpes infection rates., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited., Objective: To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis., Methods: Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated., Results: Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was -70.0% (standard deviation 33.2%) and further decreased to -76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment., Limitations: Because of the lack of a control group and observational design, factors of bias may have been induced., Conclusion: Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period., (Copyright © 2020. Published by Elsevier Inc.)

Background: Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials., Objective: To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis., Methods: PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy., Results: Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%., Limitations: Limited data in terms of size and follow-up time were available., Conclusion: Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To report two cases with corneal sterile infiltration presumably due to topical ocular hypotensive agent., Method: Case report., Results: Case 1: A 65-year-old man presented with corneal opacity and neovascularization in his left eye. A diagnosis of glaucoma was made 2 years previously, and anti-glaucoma agents were prescribed (brimonidine tartrate, ripasudil hydrochloride hydrate, and brinzolamide) for both eyes. Case 2: A 75-year-old woman noticed corneal opacity in the left eye. A diagnosis of glaucoma was made 35 years previously, and anti-glaucoma agents were prescribed (brimonidine tartrate, 1% dorzolamide, and bimatoprost) for both eyes. In both cases, ocular examination revealed follicular conjunctivitis and blepharitis in both eyes, and corneal sterile infiltration with neovascularization in the left eyes. The three topical drugs were discontinued and replaced with 0.1% fluorometholone. Both the blepharitis and corneal sterile infiltration improved thereafter, although corneal opacity remained across the stromal layer., Conclusion: We encountered two cases of corneal and conjunctival complications that were suspected as side effects after brimonidine eye drop use. Special care should be taken to observe the condition of ocular surface when topical brimonidine is administered.

Purpose: Rho-associated kinase-inhibitor ripasudil 0.4% eye drops are reportedly effective for the reduction of intraocular pressure (IOP) in glaucoma patients. However, the previous studies investigated the efficacy of IOP reduction for only about 1 year. Here, we evaluated the safety and efficacy of long-term ripasudil instillation in Japanese open-angle glaucoma (OAG) patients. Methods: This study involved 312 eyes of 312 Japanese OAG patients newly initiated with ripasudil treatment at Kyoto Prefectural University of Medicine and Oike-Ikeda Eye Clinic, Kyoto, Japan. In all patients, adverse events leading to discontinuation of ripasudil treatment were investigated. Of the 312 patients, 129 patients able to continue ripasudil administration for over 12-months post-treatment initiation were enrolled to investigate the long-term efficacy. IOP data at 0-, 1-, 3-, 6-, 12-, 18-, and 24-months post initiation of continuous ripasudil use were obtained, and the IOP values at each time point were then compared. The first period (from 1-6 months) and second period (from 12-24 months) IOP data were also compared based on the mixed model. Results: IOP at each time-point post-treatment initiation was significantly reduced compared with that at pre initiation ( P  < 0.05). Differences in IOP between the first and second periods of the study were not statistically significant ( P  = 0.058). Adverse events leading to discontinuation of treatment included blepharitis (15.7%) and conjunctival hyperemia (9.0%). Conclusions: We found that in Japanese OAG patients, 24-month ripasudil eye drop instillation is both safe and effective for lowering IOP and that blepharitis is the primary adverse event for discontinuation of use.

Competing Interests: Competing interests: None declared.

Background: The purpose of this case series was to further characterize proteasome inhibitor associated chalazia and blepharitis, to investigate outcomes of different management strategies, and to propose a treatment algorithm for eyelid complications in this patient population., Methods: This retrospective case series included sixteen patients found to have chalazia and/or blepharitis while receiving proteasome inhibitors for plasma cell disorders at Mount Sinai Hospital in New York, NY from January 2010 through January 2017. Main outcomes were complete resolution of eyelid complications and time to resolution. Student's t-test was used to compare average values and Fisher's exact test was used to compare proportions., Results: Fourteen patients had chalazia and 10 had blepharitis. Chalazia averaged 5.4 mm, and 11 patients with chalazia experienced two or more lesions. Median follow-up time was 17 months. Average time from bortezomib exposure to onset of first eyelid complication was 3.4 months. Chalazia episodes were more likely to completely resolve than blepharitis episodes (p = 0.03). Ocular therapy alone was trialed for an average of 1.8 months before proceeding to bortezomib omission. Average time to eyelid complication resolution using ocular therapy alone was 1.8 months versus 3.1 months after bortezomib omission. In this series, the combination of ocular therapy and bortezomib omission led to complete resolution of eyelid complications more often than ocular therapy alone., Conclusion: Proteasome inhibitor associated eyelid complications were identified in sixteen patients with plasma cell disorders. Eyelid complications may be treated with a 2-month trial of conservative ocular therapies alone, followed by continuation of ocular therapy in combination with bortezomib omission if eyelid signs persist.

Precis: Blepharitis was the most common side effect leading to discontinuation of ripasudil therapy. Prior allergic reactions to other topical glaucoma were found to be a risk factor for ripasudil-induced blepharitis., Purpose: To report the incidence proportion of blepharitis and its relating factors due to long-term use of 0.4% riapasudil, a Rho-kinase inhibitor, in glaucoma patients of a clinical setting., Patients and Methods: One hundred three eyes of 103 consecutive glaucoma patients who started ripasudil treatment between December 2014 and February 2017 at our institute, and who had a follow-up period of over 6 months were enrolled in this study. Incidence proportion, time required for recovery and risk factors associated with blepharitis and other side effects that led to discontinuation of ripasudil treatment were considered., Results: The most frequently observed side effect was blepharitis (25.2%). The 12- and 24-month discontinuation rate due to blepharitis was 21.1%±8.2% and 34.6%±11.8% (average±SE), respectively (Kaplan-Meier analysis). Most patients recovered from blepharitis symptoms within 4 weeks, but 5 patients required over 8 weeks for recovery. Past history of allergic reactions to other topical glaucoma medication was significantly correlated with the manifestation of blepharitis (Cox proportional hazard model, P<0.007) while age, sex, intraocular pressure reduction rate, number of administered eye drops, history of systemic allergic diseases were not., Conclusions: Blepharitis was the most common reason for discontinuation of ripasudil treatment. Although most cases were resolved spontaneously, prolonged blepharitis was observed in a few patients. A past history of allergic reaction to other glaucoma medication indicates a higher possibility of blepharitis with ripasudil use and warrants careful administration.

Case Report: A 16-year-old female patient initially presented with bilateral swelling and redness of the eyelids already existing for the duration of two days. The symptoms had started after the patient dyed her eyelashes and eyebrows with henna., Therapy: Systemic antihistamine and glucocorticoid therapy led to no visible improvement. An intravenous antibiotic treatment was started which resolved the symptoms entirely., Conclusion: The diagnosis of an allergic contact dermatitis with a secondary bacterial infection was made.

Purpose: To report a case of marginal keratitis that developed after intravitreal ranibizumab injection., Methods: A 56-year-old man with diffuse diabetic macular edema received intravitreal injection of ranibizumab into his right eye., Results: One day after injection, the patient presented with pain, redness, tearing, and discomfort in his right eye. Anterior segment examination of the right eye revealed subconjunctival hemorrhage, 3 corneal subepithelial peripheral infiltrates separated from the limbus by a clear zone, and mild anterior chamber reaction. Examination of the eyelids was remarkable for mild blepharitis. Fungal and bacterial cultures were negative. The condition resolved with topical corticosteroids and antibiotics., Conclusions: Intravitreal ranibizumab injection may trigger hypersensitivity reaction in the form of marginal keratitis in patients with mild blepharitis.

Background: Aromatase inhibitors are frequently used as an adjuvant therapy in the treatment of breast cancer. We observed that several patients taking aromatase inhibitors presented with severe dry eye symptoms, and we investigated whether there is a relationship between aromatase inhibitors and dry eyes in these patients., Design: Retrospective chart review., Participants: Forty-one women., Methods: A computerized search of health records was performed to identify patients using anastrazole, letrozole and exemestane seen by the Cornea Service from August 2008 to March 2011. The results were compared with age-matched controls., Main Outcome Measures: Ocular surface changes among aromatase inhibitors users., Results: Of the 41 women, 39 were Caucasians. Thirty-nine patients had breast cancer (95%), one patient had ovarian cancer (2.5%) and one had an unknown primary cancer. Mean age was 68 ± 11.3 years (range 47-95). Most common presenting symptoms were blurred vision in 28 (68%) patients, irritation/foreign body sensation in 12 (29%) patients, redness in 9 (22%) patients, tearing in 6 (22%) patients and photosensitivity in 2 (5%) patients. Mean Schirmer's test measurement was 11 ± 5.8 mm (range 0.5-20 mm). Blepharitis was noted in 68 of 82 eyes (73%), decreased or poor tear function in 24 eyes (29%), conjunctival injection in 18 eyes (22%) and superficial punctate keratitis in 12 eyes (29%). Among an age-matched population (45-95 years), dry eye syndrome was found in only 9.5% of patients., Conclusions: Because the prevalence of ocular surface disease signs and symptoms appears to be higher in study group than control patients, aromatase inhibitors might be a contributing factor to the dry eye symptoms., (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)

In the present study, we evaluated the ophthalmologic outcomes of 24 patients who received chemotherapy and/or radiotherapy for the treatment of non-conjunctival ocular adnexal mucosa-associated lymphoid tissue-type (MALT) lymphoma. Ophthalmologic outcomes were assessed in patients who received chemotherapy and/or radiotherapy from March 2004 until May 2010. Outcomes were determined according to common symptoms following chemotherapy and/or radiotherapy, which consisted of decreased visual acuity, dry eye symptoms, retinopathy, optic neuropathy, increased intraocular pressure, and blepharitis. Nine patients received chemotherapy alone, eight patients received radiotherapy alone, and seven patients received chemotherapy with additional radiotherapy (chemoradiation therapy). Patients treated by chemotherapy alone showed better ophthalmologic outcome scores (mean score, 1.56) than those treated by radiation alone or chemoradiation therapy (mean score, 4.01). In conclusion, the treatment of ocular adnexal lymphoma including radiotherapy showed poor ophthalmologic outcomes due to radiation-induced complications. Recently, many new treatment options have emerged, such as immunotherapy or radioimmunotherapy. In the future study, to select a better treatment modality with fewer complications, well-designed prospective trials with ophthalmologic outcomes are needed.

Para-phenylenediamine (PPD) can induce immediate or - more often - delayed hypersensitivity. We report the case of 48-year old female admitted to the out-patient allergy clinic a day after her visit in a beauty parlour, where she had her eyelashes and eyebrows dyed with henna. Physical examination revealed prominent edema of the upper part of the face including forehead, cheeks and eyes causing severe narrowing of the palpebral chink. Skin prick tests (SPT) with common allergens were positive for Dermatophagoides pteronyssinus, Dermatophagoides farinae and moulds, while the SPT with PPD was negative. Patch test to PPD was positive. Further investigations revealed eosinophilia in the tear fluid. To our knowledge, this is the first case of PPD-induced contact blepharoconjunctivitis (CB) with concomitant increased eosinophilia in the tear fluid.

Background: Even though air pollutants exposure is associated with changes in the ocular surface and tear film, its relationship to the clinical course of blepharitis, a common eyelid disease, had not yet been investigated. Our objective was to investigate the correlation between air pollution and acute manifestations of blepharitis., Method: We recorded all cases of changes in the eyelids and ocular surface, and rated clinical findings on a scale from zero (normal) to two (severe alterations). Daily values of carbon monoxide, particulate matter smaller than 10 μm in diameter and nitrogen dioxide concentrations and meteorological variables (temperature and relative humidity) in the vicinity of the medical service were obtained. Specific linear regression models for each outcome were constructed including pollutants as independent variables (single pollutant models). Temperature and humidity were included as confounding variables., Results: increases of 28.8 μg/m(3) in the concentration of particulate matter and 1.1 ppm in the concentration of CO were associated with increases in cases of blepharitis on the day of exposure (5 cases, 95% CI: 1-10 and 6 cases, 95% CI: 1-12, respectively)., Conclusion: Exposure to usual air pollutants concentrations present in large cities affects, in a consistent manner, the eyes of residents contributing to the increasing incidence of diseases of the eyelid margin., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the microbiological characteristics of eyelid margin flora in chronic blepharitis in mustard gas-exposed individuals and compare the results with those in age- and sex-matched unexposed people., Methods: In this comparative case series, 289 patients with ocular manifestations of mustard gas exposure (case) were evaluated for signs of chronic blepharitis. Additionally, microbiological evaluation of eyelid margins was conducted in these patients and compared with results of 100 unexposed patients with chronic blepharitis (control)., Results: One-hundred fifty (52.0%) of 289 mustard gas casualties had signs of chronic blepharitis. Microbiological evaluation revealed higher isolation rates of Staphylococcus epidermidis (78%) and Staphylococcus aureus (57%) in the case in comparison to control group (P < 0.01). Moreover, S. aureus isolated from the cases exhibited greater resistance to common antibiotics compared with control group. Fungi were isolated more frequent in the case compared with controls (30% vs. 4%, P < 0.01), with Cladosporium and Candida species being most common in the case group., Conclusions: Exposure to mustard gas seems to alter the microbiological flora of the eyelid margin. Staphylococcus spp., including antibiotic-resistant strains, and fungi were more frequently isolated in these patients. The relationship between microbial culture results and the severity of ocular surface manifestations in mustard gas-injured cases warrant further investigation.

Topical eye-drops remain the cornerstone of treatment for ocular diseases, including glaucoma. Preservatives are added to multi-dose medication bottles to reduce the risk of microbial contamination, to extend the validity of the product and to allow an easily use of the bottles. However the repetitious use of ophthalmic medications containing preservatives, particularly when treating chronic diseases, has been linked to adverse effects and ocular surface disease (OSD). Therefore, this presentation provides an overview of glaucoma and OSD, the role of preservatives in ophthalmic preparations, and the impact of preservatives on the ocular surface.

This report describes the case of a 41-year old woman in treatment for advanced colorectal cancer who developed severe bilateral blepharitis and trichomegaly after the second dose of cetuximab. Cetuximab-related eyelid toxicity has been described previously; however, its pathogenesis has not yet been clearly established.

Purpose: The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment., Methods: A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits., Results: Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected., Conclusions: Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.

Allergic contact dermatitis due to mydriatic eyedrops is rare despite extensively used by ophthalmologists. Phenylephrine is responsible for most of the cases in the literature. We reported two other cases due to phenylephrine eyedrops with an unusual evolution characterized by chronic debilitating blepharoconjunctivitis.

Purpose: To evaluate the ocular surface changes and tear-film functions in patients treated with systemic isotretinoin., Methods: Fifty subjects treated with 0.8 mg/kg oral isotretinoin were enrolled in this prospective clinical trial. All patients underwent a full ophthalmoscopic examination before, during, and after treatment with isotretinoin. Ocular surface changes of the cell content of the surface conjunctival epithelium were evaluated by conjunctival impression cytology and tear-film functions using the Schirmer test, anesthetized Schirmer test, tear breakup time, and rose bengal staining. Subjective ocular complaints were scored with an Ocular Surface Disease Index questionnaire., Results: There were no significant differences observed in average Schirmer test scores for patients before, during, or after isotretinoin treatment. Mean anesthetized Schirmer test scores and tear breakup time decreased significantly during treatment (P < 0.001). Mean impression cytology scores, Ocular Surface Disease Index scores, and rose bengal staining scores increased significantly during treatment (P < 0.05, P < 0.001 and P < 0.001, respectively). Blepharitis was seen in 36% of patients. All abnormal findings disappeared 1 month after the cessation of treatment., Conclusions: Conjunctival epithelial cells, tear basal secretion, and tear quality are markedly affected in patients during systemic treatment with isotretinoin (0.8 mg/kg). Ocular adverse effects of isotretinoin are generally not serious and are reversible after discontinuation.

Background: Contact allergies (CA) against active agents of topical ophthalmological therapeutics, causing inflammation of the conjunctiva and/or the lid, are usually not life-threatening, but occur not infrequently. As yet, the assessment of the CA-eliciting risk has been based on clinical data alone, while a valid epidemiological risk assessment is lacking., Materials and Methods: The Information Network of Departments of Dermatology supplied information on diagnostic results obtained in 4,102 patients patch-tested for suspected CA to ophthalmic drugs between 1995 and 2004. Clinical prevalences were extrapolated to incidences at the German population level. These estimates served as numerator for a relative incidence (RI), which included the nationwide frequency of prescriptions collected by the WIdO, Bonn, in terms of a standardised defined daily dose (DDD) as denominator., Results: The estimated annual incidence of CA ranges from 155 (atropine sulphate) to 2077 (gentamicin sulphate) and can thus be regarded as moderate. If incidence estimates are related to prescription frequencies, the highest risk was found for kanamycin and neomycin sulphate (RI > 8 / 100,000 DDD). In contrast, the RI of pilocarpine-HCl (0.3) was virtually negligible., Conclusions: The substance-specific risk of CA has been evaluated for the first time and found to differ between therapeutics (with a similar spectrum of application). CA risk should be considered in differential therapeutic decision-making.

Case Report: A 52-year-old woman with advanced colorectal cancer was referred to us for treatment of Cetuximab-related ocular side-effects., Discussion: Cetuximab is a monoclonal antibody that specifically blocks epidermal growth factor receptor activity. It has recently been approved to treat some tumors such as metastatic colorectal cancer and some ORL cancers. Tolerance to it seems to be better than that to the classic chemotherapeutic agents. However it has several side-effects. Cetuximab-related eyelid toxicity has been recently described, though the pathogenesis has not yet been clearly established.

Purpose: To report the external ocular changes in 2 patients receiving epidermal growth factor receptor (EGFR) inhibitors., Methods: Retrospective observational case series. Two patients receiving epidermal growth factor inhibitors for metastatic non-small-cell lung carcinoma were followed clinically and with external photographs., Results: Findings included acneiform facial changes, telangiectasia of eyelid margins, meibomitis, tear film dysfunction, and unusual, hyperpigmented, tortuous eyelashes., Conclusions: EGFR inhibitors used in the treatment of certain malignancies can lead to symptomatic adnexal and ocular surface changes. Ophthalmologists should be aware of these to appropriately manage them.

Allergic reactions to midriatic eyedrops are rare despite extensively used by ophthalmologists. Phenylephrine is responsible for 54-95% of cases reported in literature. We present the case of a 56-year-old man with blepharoconjunctivitis after instillation of phenylephrine 5%, tropicamide 0.5%, oxibuprocaine eyedrops. The patient reported good tolerance to the mentioned drugs. Immediate readings of prick and intradermal tests, performed with the suspected drugs, were negative. Late readings (48 and 72 hours) of epicutaneous tests were also negative. At 72 hours, prick and intradermal tests to phenylephrine were positive. Allergic blepharoconjunctivitis to phenylephrine was diagnosed. Phenylephrine is an extensively used midriatic that can act as a potent sensitizing agent and can be the cause of allergic contact reactions in exposed patients. With this case we illustrate the relevance of late readings of intradermal tests in the diagnosis of late hypersensitivity drug reactions. The authors discuss about possible mechanisms responsible for negative results of epicutaneous tests.

Epidermal growth factor receptor (EGFR) inhibitors have become an important therapy for patients with malignant solid tumors, such as non-small cell lung, breast, ovarian, colorectal, renal, esophageal, sarcoma, mesothelioma, prostate, head and neck, and pancreatic cancers. Although these agents are generally well tolerated, some adverse effects will likely occur. The most common adverse effect associated with use of EGFR inhibitors is an acne-like rash. Less reported in the literature are adverse ocular reactions, which occur in approximately one third of patients and can cause significant discomfort. The ocular toxicities that may occur with use of EGFR inhibitors can be broadly categorized as changes in the eyelids (eg, squamous blepharitis, trichomegaly, meibomitis), changes in the tear film (eg, dysfunctional tear syndrome), and miscellaneous changes (eg, iridocyclitis, corneal epithelial defect). Early recognition and management of these adverse ocular reactions are necessary to improve patient comfort, to facilitate compliance, and to avoid interruption of therapy. This article describes the adverse ocular effects reported to occur with use of EGFR inhibitors and presents specific strategies to manage these effects. Mild eyelid and tear film changes usually can be managed by the oncology and nursing staff. More severe ocular reactions require involvement of an ophthalmologist.

Purpose: Retrobulbar chlorpromazine injection is a relatively recently described method of pain control in nonseeing eyes. This report illustrates severe sterile inflammation as a potential complication., Methods: In this university-based, retrospective, small case series, we reviewed the records of 2 female patients and 1 male patient (ages, 13 to 89 years) who developed severe inflammation after retrobulbar chlorpromazine injection., Results: Three patients had development of severe periocular edema after retrobulbar chlorpromazine injection. Two had development of chemosis, limited extraocular motility, proptosis, and incomplete eyelid closure, necessitating temporary tarsorrhaphy. The third patient had development of facial edema involving the ipsilateral eyelids, forehead, and cheek. Strikingly, it extended to the contralateral face. All 3 patients denied discomfort. In each case, swelling was first noted the day after injection and progressed for 1 week. All were treated with topical lubrication and two with temporary tarsorrhaphy. Resolution occurred within 3 weeks in each case., Conclusions: Severe periocular inflammation can result from retrobulbar chlorpromazine injection and may manifest as chemosis, proptosis, limited ocular motility, and facial swelling that may extend well beyond the eyelids. Awareness of this potential adverse reaction is important both for patient counseling before injection and subsequent treatment. Specifically, a sterile inflammatory response should be differentiated from infection to avoid inappropriate therapy.

Purpose: To report a case of severe blepharoconjunctivitis induced by a peeling mask., Methods: A 32-year-old healthy female was examined one day after undergoing a face-peeling procedure with a mask containing trichloroacetic acid. She complained of severe burning, redness, and epiphora in her left eye that started several hours after the procedure., Results: Her vision was LE 0.2, RE 0.8. Mild upper eyelid edema of the right eye and severe edema of the left eyelids, LE inferior ectropion, and LE blepharoconjunctivitis were noted. The conjunctiva was severely hyperemic with papillary reaction and chemosis. The corneas, anterior chambers, irides, lenses, and posterior segments were normal. The patient was treated with Dexamethasone 0.1% q2h and ocular lubrication. The reaction subsided after 3-4 days., Conclusion: Face-peeling masks containing trichloroacetic acid can sometimes severely irritate the eyelids and the ocular surface.

Background: Periorbital allergic contact dermatitis is a rare disease and the main differential diagnoses are atopic and seborrhoeic dermatitis. The diagnosis is based on clinical appearance, patient history and patch testing. Current systematic overviews on contact allergens involved are lacking and with changes in medical preparations, new relevant antigens may emerge., Patients and Methods: Based on the systematic data of the information network of dermatological clinics (IVDK), patch test reactions in 48,969 patients tested between 1996 and 2000 were evaluated. A total of 763 patients suffered from periorbital dermatitis which was suspected to be due to the use of topical medication., Results: The most common epidermal sensitizations in the general population were observed against nickel and fragrances. In the periorbital dermatitis group, sensitization against local anaesthetics and antibiotics was more frequent than in the general population., Conclusions: In three patients, oxybuprocain was identified as the causative agent, which has not yet been recognized as a common allergen.

Background: How the early phase allergic reaction affects the late phase reaction remains unclear. We examined this issue with an experimental model of allergic conjunctivitis that permits the two reactions to be disconnected from each other., Methods: Experimental immune-mediated blepharoconjunctivitis (EC) was initiated in Brown Norway rats by transferring ovalbumin (OVA)-specific T cells and then challenging with OVA-containing eye drops. To induce early phase reaction, a mast-cell activator, C48/80, was challenged together with or without OVA. Rats were evaluated clinically and eyes were harvested for histologic examination and for evaluation of chemokine expression by reverse-transcriptase PCR., Results: The rats challenged with OVA alone developed the T-cell-mediated late phase reaction histologically, but not clinically, in the absence of early phase reaction. While rats challenged with C48/80 with or without OVA exhibited clinical signs of the early phase reaction, the clinical late phase reaction was observed only in the OVA+C48/80 group. Eosinophilic infiltration into the conjunctiva during the late phase reaction of the OVA+C48/80 group markedly exceeded that of rats challenged with either OVA or C48/80 alone. RANTES (regulated on activation, normal T-cell expressed and secreted), an eosinophil attractant, was expressed both in the OVA+C48/80 and OVA groups, while eotaxin was expressed at equivalent levels in all three groups., Conclusion: The mast-cell-mediated early phase reaction potentiates the T-cell-mediated late phase reaction, and RANTES is involved in eosinophilic infiltration induced by antigen-specific T cells. Other molecules induced by allergen-specific T cells activated in an as yet unknown manner by the mast cells may be responsible for the infiltration of eosinophils.

Background: Phenylephrine and pseudoephedrine are sympathomimetic drugs belonging to the phenylamine family. Adverse cutaneous effects associated with these drugs have been reported but, in view of their frequent use, appear to be rare. The very close chemical structures of these drugs could explain potential cross-reactions among them but the results reported in the literature are controversial., Case Report: An 18-year-old woman developed blepharoconjunctivitis after application of phenylephrine and tropicamide eye drops. Four years after this reaction, she took 1 tablet of Narine (pseudoephedrine and loratadine) and 3-4 hours later developed a generalized erythrodermic reaction. Cutaneous biopsy revealed hydropic changes in the basal layer and, in the dermis, moderate edema with slight perivascular lymphocyte and eosinophil infiltrates. Patch tests with European standard series, commercial eye drops, tropicamide, phenylephrine, pseudoephedrine and other sympathomimetic agents were applied to the patient's back. After 47 and 96 hours, only the patches with pseudoephedrine and phenylephrine were positive., Conclusions: We believe that our patient has presented two different reactions with different clinical outcome and histopathology, which are unlikely to be due to cross-reactivity between the drugs involved. We have found no similar coincidences reported int the literature.