Possible Association Between Apremilast Therapy and Increased Tearing.

PURPOSE: To evaluate a possible association between apremilast and increased tearing. METHODS: A retrospective observational case series in which reports from VigiBase, the World Health Organization global database of Individual Case Safety Reports, and the literature involving apremilast were evaluated by the National Registry of Drug-Induced Ocular Side Effects for possible increased tearing. RESULTS: A total of 45 cases of possible apremilast-induced increased tearing were identified. All patients were on the standard dose of 30 mg BID. There was no sex difference and ages ranged from 28 to 77 years with an average of 56 years ± 12. Time to onset of the increased tearing ranged from a few days to many months. There were 10 cases of positive dechallenge, 3 cases of positive rechallenge, and 1 case with double-positive rechallenge. In the cases with positive dechallenge and rechallenge, the increased tearing resolved as early as within 2 days after stopping the drug. Most cleared within 2 weeks. One case required 3 months for tearing to return to normal. CONCLUSIONS: Based on patterns and positive dechallenge and rechallenge data, apremilast possibly causes increased tearing on rare occasions.

Oral Anti-Vascular Endothelial Growth Factor Drugs and Ocular Adverse Events.

PURPOSE: To evaluate possible associations between oral anti-vascular endothelial growth factor (VEGF) drugs and ocular side effects. METHODS: Spontaneous reports were collected and evaluated by the National Registry of Drug-Induced Ocular Side Effects on the three oral anti-VEGF drugs (pazopanib, sorafenib, and sunitinib) for possible ocular side effects. RESULTS: Reported side effects include blurred or decreased vision (389 cases); periocular or eyelid edema (273 cases); superficial anterior segment toxicity (270 cases); conjunctival, retinal, or vitreous bleeding (77 cases); retinal detachments (RDs) or retinal tears (RTs) (75 cases); extraocular muscle disorders, including ptosis (51 cases); discoloration of eyelashes (36 cases); retinal arterial or venous occlusions (26 cases); optic nerve disorders, including papilledema and ischemic optic neuropathy (21 cases); uveitis (10 cases); and macular edema (7 cases). Spontaneous reports of possible RD or RT have been associated with pazopanib (31 RDs and 12 RTs), sunitinib (24 RDs and 0 RT), and sorafenib (7 RDs and 2 RTs). CONCLUSIONS: Oral anti-VEGF drugs can cause superficial anterior segment side effects. Pazopanib has been reported to be possibly linked to RDs and RTs. This study suggests that sorafenib and sunitinib are suspected as well. RDs were seldom differentiated into rhegmatogenous retinal detachments (RRDs) or non-RRDs. The association of oral anti-VEGF drugs with RRD and RT are unclassified although this suggests a "signal" requiring further study. The association of oral anti-VEGF drugs with serous retinal detachments, while rare, is plausible. Patients on this class of drugs should be instructed to seek immediate ophthalmic consultation if retinal symptoms occur.

Atypical Optic Neuritis After Inactivated Influenza Vaccination.

The existence of vaccine-associated optic neuritis is essentially based on the temporal relationship between the administration of a vaccine and the development of optic neuritis in patients with no other known aetiologies for infectious or non-infectious inflammation that could account for the optic neuritis. Influenza vaccine (inactivated or live attenuated) is considered to be one of vaccines that could be related to optic neuritis. The authors describe a rare case of bilateral asymmetric optic neuritis with leptomeningeal enhancement on magnetic resonance imaging (MRI) in a previously healthy young woman who received inactivated influenza vaccination 2 weeks before the onset of symptoms.

Liquid Nitrogen Cryotherapy Treatment of Herpes Simplex Epithelial Keratitis.

A retrospective case series was performed in a university setting for all patients with herpes simplex epithelial keratitis who underwent liquid nitrogen cryotherapy from 2012-2015. Outcome measure was clinical evidence of resolution of epithelial keratitis in the cornea with re-epithelialization. All cases of epithelial keratitis showed partial and complete resolution at day 1 and week 1 respectively. Liquid nitrogen cryotherapy is a safe and effective treatment for herpes epithelial keratitis comparable to other published studies.

Vaccine-Associated Uveitis.

All of the widely administered vaccines have been reported to cause uveitis. The ocular inflammation is usually temporary and resolves with topical ocular steroids. During a 26-year period, a total of 289 cases of vaccine-associated uveitis were reported to three adverse reaction reporting databases. Hepatitis B vaccine, either alone or administered with other vaccines, appears to be the leading offender. Clinicians are encouraged to report cases of vaccine- or drug-associated ocular adverse reactions to www.eyedrugregistry.com.

Association Between Bortezomib Therapy and Eyelid Chalazia.

IMPORTANCE: Spontaneous reports to the National Registry of Drug-Induced Ocular Side Effects and case reports in the literature suggest an association between bortezomib use and chalazia. OBSERVATIONS: To our knowledge, there have been 24 reports of bortezomib-associated chalazia. Fourteen reports were collected from the National Registry of Drug-Induced Ocular Side Effects. These reports originated at the US Food and Drug Administration's Adverse Event Reporting System or at the World Health Organization's Uppsala Monitoring Centre. An additional 10 case reports were found in the literature. The mean age of the 24 patients was 61 years (age range, 37-79 years), 8 were female and 11 were male (the sex was unknown in 5), and the mean duration of bortezomib therapy before the onset of chalazia was slightly more than 3 months (range, 26-428 days; mean, 98 days). Chalazia were usually multiple and involved the upper eyelid. Recommendations for the bortezomib dosages were within the package insert. Most patients were receiving multiple medications. There were 8 positive dechallenge case reports and 3 positive rechallenge case reports. CONCLUSIONS AND RELEVANCE: Using the World Health Organization's classification for adverse drug reactions, the association between bortezomib use and chalazia is classified as possible. This conclusion is based on the finding that chalazia improved or resolved in most patients when bortezomib was discontinued, the temporal relationship between initial administration of bortezomib and chalazia onset, and the positive dechallenge and rechallenge data.

Dry eye in LASIK patients.

BACKGROUND: Increasing age is a known risk factor for developing dry eye. The specific aims of the present study were to determine the prevalence of dry eye syndrome (DES) and use of post-operative dry eye medications in a relatively young population presenting for LASIK surgery at an academic ophthalmology clinic. FINDINGS: A retrospective, analysis of 948 de-identified patient charts (median age 39 years, not age stratified) was performed to extract pre-LASIK diagnoses and post-LASIK medication lists. Clinical evaluation for DES and the results of Schirmer's reflex tear flow test were used to assign LASIK patients into Normal, Pre-dry eye (Pre-DES), and Dry Eye Syndrome (DES) groups; which were then compared for use of dry eye medications.Based on pre-operative diagnoses, only 2% (CI: 1.3 - 3.1) of LASIK patients presented with overt DES. Unexpectantly, 25% (CI: 22.2 - 27.6) of LASIK patients labeled Pre-DES were not classified by the clinician as having overt DES, yet they showed poor reflex tear flow rates ≤ 5 mm before surgery, and frequently used post-operative lubricant dry eye medications. CONCLUSIONS: Although the number of patients with pre-existing eye conditions was unknown, a sizable portion of relatively young LASIK patients displays poor reflex tear flow without overt DES. Such patients could go on to develop more serious consequences of poor tear flow, such as corneal abrasion and erosion. More specific, dry eye medications may be needed for ideal treatment.

Human papilloma virus vaccine associated uveitis.

PURPOSE: To report a possible association between human papilloma virus (HPV) vaccination and uveitis. METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." MAIN OUTCOME MEASURES: Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. RESULTS: A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). DISCUSSION: According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

Conjunctival and corneal ulceration associated with nicorandil.

CONTEXT/OBJECTIVE: To report an association between conjunctival and corneal ulceration and nicorandil therapy for angina. METHODS: Review of the literature and spontaneous reports collected at the National Registry of Drug-Induced Ocular Side Effects (Portland, Oregon), the FDA Spontaneous Reporting System (Bethesda, Maryland) and the World Health Organization's Uppsala Monitoring Center (Uppsala, Sweden). RESULTS: Thirteen case reports of adverse ocular reactions were collected. Abnormal vision (5 reports), corneal ulcer (4 reports) and conjunctival ulcer (4 reports) were associated with nicorandil. Eight subjects were male and 5 female with an average age of 75.4 ± 8.3 years. The average duration of therapy to development of the ADR was 30.4 days ±3 days. Eleven case reports had positive dechallenge and the patients fully recovered. The average dose was 21.6 mg daily. CONCLUSION: Using WHO classification for adverse drug reactions, the association between nicorandil and conjunctival and corneal ulceration is "possible". The case reports indicate that, if recognized, withdrawing nicorandil will lead to resolution of the conjunctival or corneal ulceration. Advanced age and accumulation of nicotinic acid in tissues may be contributory to the risk of developing ocular ulcerations from nicorandil.

Toxicity of topical ophthalmic anesthetics.

INTRODUCTION: Topical ocular anesthetics are generally well tolerated in clinical settings but have great potential for abuse if used by patients at home. This abuse can lead to significant ocular complications. Topical ocular anesthetic abuse can lead to superficial punctate keratitis, persistent epithelial defects, stromal/ring infiltrates, corneal edema, endothelial damage and ocular inflammation, even when used in a dilute concentration. Patient characteristics may include a healthcare association and/or psychiatric illness. In these instances, patients often do not admit to anesthetic use and are often initially treated for acanthamoeba keratitis. Local anesthetics are thought to cause direct toxicity to the corneal epithelium, stroma and endothelium. This in turn may lead to release of antigens and from there an inflammatory response in the form of infiltrate and edema. It is thought that preservatives in anesthetics may play a further role in toxicity. AREAS COVERED: The authors provide a brief history on topical ocular anesthetics and review the most recent literature on reported ocular toxicities of topical anesthetics. EXPERT OPINION: Practitioners must maintain high suspicion for topical ocular anesthetic abuse to identify it early. Topical ocular anesthetic abuse is often misdiagnosed as acanthamoeba keratitis. Early identification is one of the most important factors for a successful outcome. It is also imperative to give proper alternative pain control to avoid topical anesthetic abuse.

Initiation of anti-TNF therapy and the risk of optic neuritis: from the safety assessment of biologic ThERapy (SABER) Study.

PURPOSE: To evaluate the incidence of optic neuritis (ON) in patients using anti-tumor necrosis factor (TNF) alpha therapy. DESIGN: Retrospective, population-based cohort study. METHODS: We identified new users of anti-TNF therapy (etanercept, infliximab, or adalimumab) or nonbiologic disease-modifying antirheumatic drugs (DMARDs) during 2000-2007 from the following data sources: Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and National Medicaid/Medicare. Within this cohort, we used validated algorithms to identify ON cases occurring after onset of new drug exposure. We then calculated and compared ON incidence rates between exposure groups. RESULTS: We identified 61 227 eligible inflammatory disease patients with either new anti-TNF or new nonbiologic DMARD use. Among this cohort, we found 3 ON cases among anti-TNF new users, occurring a median of 123 days (range, 37-221 days) after anti-TNF start. The crude incidence rate of ON across all disease indications among anti-TNF new users was 10.4 (95% CI 3.3-32.2) cases per 100 000 person-years. In a sensitivity analysis considering current or past anti-TNF or DMARD use, we identified a total of 6 ON cases: 3 among anti-TNF users and 3 among DMARD users. Crude ON rates were similar among anti-TNF and DMARD groups: 4.5 (95% CI 1.4-13.8) and 5.4 (95% CI 1.7-16.6) per 100 000 person-years, respectively. CONCLUSION: Optic neuritis is rare among those who initiate anti-TNF therapy and occurs with similar frequency among those with nonbiologic DMARD exposure.

Bilateral uveitis associated with fluoroquinolone therapy.

CONTEXT: Retrospective case series, database study and literature review. Forty case reports are described. OBJECTIVE: To report a possible association between fluoroquinolones and uveitis. MATERIALS AND METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization, and Food and Drug Administration were collected on uveitis associated with systemic fluoroquinolone therapy. A literature review was performed using keywords "uveitis", "fluoroquinolones", and each individual fluoroquinolone name. Additional case reports were collected from the practices of six uveitis subspecialists and one neuro-ophthalmologist. MAIN OUTCOME MEASURES: Data garnered from the reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of uveitis, concomitant drugs, systemic disease, dechallenge and rechallenge data. RESULTS: A total of 40 case reports of uveitis associated with fluoroquinolones were identified including 12 men, 27 women, and 1 case in which the gender was not specified. The median age was 54 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 13 days (range 0-20 days). Thirteen patients were 60 years or older, and one patient was taking systemic anti-inflammatory steroids. There were five positive dechallenge case reports. DISCUSSION: According to World Health Organization criteria, the relationship between fluoroquinolone therapy and uveitis is "possible". Causality assessments are based on the time relationship of drug administration, uveitis development, and dechallenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral fluoroquinolone-associated uveitis, particularly the finding of iris transillumination and pigment dispersion.

Trichomegaly and other external eye side effects associated with epidermal growth factor.

CONTEXT/OBJECTIVE: To report an association between epithelial growth factor receptor (EGFR) inhibitors and ocular side effects. MATERIALS AND METHODS: Collection of spontaneous reports at the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon) in conjunction with a literature review of EGFR inhibitors associated with ocular adverse drug reactions (ADR). RESULTS: EGFR inhibitors are associated with conjunctivitis, meibomitis, dry eyes, periocular skin changes and trichomegaly. EGFR inhibitors may also cause superficial punctate corneal changes and corneal erosions. DISCUSSION: This is the first overview of all known ocular side effects associated with the use of marketed EGFR inhibitors. This is also the first effort for this class of drugs using the World Health Organization Classification as to causality. CONCLUSION: Ophthalmologists should be aware of possible adverse ocular side effects from EGFR inhibitors and treat based on the type of ADR encountered. All ocular side effects noted are fully reversible upon discontinuation of the drug.

Use of herbal medicines and nutritional supplements in ocular disorders: an evidence-based review.

We sought to examine the evidence regarding the use of herbal medicines and nutritional supplements in age-related macular degeneration (AMD), cataracts, diabetic retinopathy and glaucoma, and to review the ocular adverse effects of herbal and nutritional agents of clinical importance to ophthalmologists. We performed a literature search of Ovid MEDLINE and selected websites including the American Academy of Ophthalmology (AAO), the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH) and the World Health Organization (WHO). There is strong evidence supporting the use of antioxidants and zinc in patients with certain forms of intermediate and advanced AMD. However, there has been growing evidence regarding potential significant adverse effects associated with the AREDS (Age-Related Eye Disease Study) formula vitamins. Current data does not support the use of antioxidants or herbal medications in the prevention or treatment of cataracts, glaucoma or diabetic retinopathy. It is important for providers to be aware of the benefits and the significant potential adverse effects that have been associated with nutritional supplements and herbal medications, and to properly inform their patients when making decisions about supplementation. Further rigorous evaluation of nutritional supplements and herbal medicines in the treatment of eye disease is needed to determine their safety and efficacy.