Frederick W. Fraunfelder

Ocular adverse effects associated with systemic medications : recognition and management.

This article reviews several retrospective case series and reported adverse events regarding common ocular adverse effects related to systemic therapy. It is not intended as a comprehensive summary of these well described adverse drug reactions, nor is it intended to cover the complete spectrum of all ocular adverse effects of systemic therapy. Many systemic drugs may produce ocular toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine, tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction agents and some herbal medications. For this review, the certainty of the adverse effect profile of each medication was evaluated according to the WHO Causality Assessment Guide.A certain relationship has been established for pamidronate and alendronate as causes of scleritis, uveitis, conjunctivitis and blurred vision. Topiramate has been established as adversely causing symptoms consistent with acute angle-closure glaucoma, typically bilateral. Vigabatrin has been shown to cause bilateral irreversible visual field defects attributed to underlying medication-induced retinal pathology. Isotretinoin should be considered in the differential diagnosis of any patient with pseudotumour cerebri. Patients taking amiodarone and hydroxychloroquine should be monitored and screened regularly for development of optic neuropathy and maculopathy, respectively. Sildenafil has been reported to cause several changes in visual perception and is a possible, not yet certain, cause of anterior ischaemic optic neuropathy. Patients taking tamoxifen should also be monitored for development of dose-dependent maculopathy and decreased colour vision. COX-2 inhibitors should be included in the differential diagnosis of reversible conjunctivitis. Several herbal medications including canthaxanthine, chamomile, datura, Echinacea purpurea, Ginkgo biloba and liquorice have also been associated with several ocular adverse effects.It is the role of all healthcare professionals to detect, treat and educate the public about adverse reactions to medications as they are an important health problem.

Scleritis and other ocular side effects associated with pamidronate disodium.

PURPOSE To evaluate reported cases of scleritis and other ocular side effects associated with pamidronate disodium, with emphasis on previously unreported cases of scleritis. DESIGN Observational case series. METHODS Case reports from the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute), the Food and Drug Administration, the World Health Organization, and the literature were reviewed to determine possible adverse ocular side effects associated with pamidronate disodium. The World Health Organizations Causality Assessment Guide was used to categorize an adverse drug reaction. RESULTS Seventeen cases of unilateral scleritis and one case of bilateral scleritis occurred, usually within 6 hours to 2 days after intravenous pamidronate disodium. Six patients had positive rechallenge testing with the scleritis occurring after a repeat drug exposure. Other ocular side effects with positive rechallenge data, associated with pamidronate disodium, include blurred vision, nonspecific conjunctivitis, ocular pain, bilateral anterior uveitis, and episcleritis. CONCLUSIONS This is the first report, with rechallenge data, of any drug causing scleritis. Pamidronate disodium can cause vision-threatening diseases, which may require discontinuing the drug in some uveitis cases and, in this series, all cases of scleritis.

Bisphosphonates and ocular inflammation.

To the Editor: Bisphosphonates are used to inhibit bone resorption in postmenopausal women and to manage hypercalcemia associated with osteolytic bone cancer, metastases of breast cancer, multiple ...

Ocular Side-Effects Associated with Imatinib Mesylate (Gleevec®)

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science Universitys Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Comparison of Femtosecond Laser-assisted Keratoplasty versus Conventional Penetrating Keratoplasty

PURPOSE To compare postoperative outcomes for femtosecond laser-assisted keratoplasty (FLAK) with conventional penetrating keratoplasty (PK). DESIGN Retrospective, comparative surgical series. PARTICIPANTS Fifty consecutive patients who underwent FLAK and 50 case-controlled patients that had PK at the Casey Eye Institute (Oregon Health & Science University, Portland, OR). METHODS Data was collected for 50 consecutive cases that underwent zigzag incision FLAK and was compared with 50 subjects that had conventional blade trephine incision PK with similar age, diagnosis and concurrent ocular morbidities over a 2-year follow-up period. MAIN OUTCOME MEASURES Topographic astigmatism, best spectacle-corrected visual acuity, uncorrected visual acuity, pinhole visual acuity, and the timing of selective suture removal (or adjustment) over various follow-up intervals up to 2 years postoperatively. RESULTS Significantly lower topographic astigmatism was achieved in the FLAK group over the PK group in the 4- to 6-month follow-up period (P = 0.0324), which correlated well with significant earlier selective suture removal that occurred in that same group over both the 2- to 3-month (P = 0.0025) and 4- to 6-month (P = 0.0236) follow-up periods. This difference in astigmatism was no longer present at any other follow-up period up to 24 months postoperatively. The subset analysis of patients with keratoconus or post-LASIK ectasia did not show any difference in either astigmatism or visual acuity at any time. CONCLUSIONS Compared with PKP, FLAK had significant improvement in astigmatism before but not after the 6 month postoperative follow-up period. Earlier suture removal was noted in the FLAK group. No significant improvement in best spectacle-corrected visual acuity was noted at any time point. There were no complications or difficulties with trephination in the FLAK procedure across a wide range of corneal pathologies.

Laser-assisted in situ keratomileusis complications in diabetes mellitus

Purpose. To report the incidence of complications and the refractive results in patients with diabetes mellitus treated with laser-assisted in situ keratomileusis (LASIK). Methods. A retrospective review of the charts, focusing on 6-month postoperative data, was performed on 30 eyes from patients with diabetes and 150 age- and gender-matched control eyes operated on during the same period. The incidence of complications and postoperative refractive results were compared. The data analyzed include UCVA, spherical equivalent, astigmatism power, astigmatism axis, and vector astigmatism change. Results. Diabetic eyes treated with LASIK had an overall complication rate of 47% compared with the control population complication incidence of 6.9% (p < 0.01). The most frequent complications occurring in the diabetic population are punctate epithelial erosions and persistent epithelial defects. Spherical correction change was −4.64 diopters (D) for diabetic eyes and −4.98 D for control eyes (p = 0.49). Mean spherical equivalent change was −4.69 D for diabetic eyes and −4.75 D for control eyes (p = 0.9). Mean change in uncorrected visual acuity (LogMAR) was 1.5 for diabetic eyes and 1.65 for control eyes (p = 0.18). Mean astigmatism magnitude change was 0.31 in diabetic eyes and 0.57 in control eyes (p = 0.12). Mean vector corrected astigmatism change was 0.97 for diabetic eyes and 1.12 for control eyes (p = 0.31). Mean vector-corrected astigmatism axis for patients with diabetes was 18.17 for diabetic eyes and 6.20 for control eyes (p = 0.30). Conclusion. Patients with diabetes who undergo LASIK are at a significantly higher risk of developing postoperative epithelial complications. In addition, this study revealed poorer refractive results in the eyes of patients with diabetes treated with LASIK.

Drug-induced Uveitis : Incidence, prevention and treatment

SummaryDrug-induced uveitis is a relatively rare occurrence. For example, the patient database at the tertiary referral Uveitis Clinic at the Casey Eye Institute, Oregon Health Sciences University records an incidence of less than 0.5%. Despite this, the frequency of uveitis secondary to rifabutin therapy in AIDS patients has brought greater recognition to the potential role of medications as a cause of intraocular inflammation.A brief review of uveitis including its classification, causes, symptoms and signs is presented along with a review of systemic medications associated with uveitis. These medications include cidofovir, cobalt, diethylcarbamazepine, pamidronic acid (disodium pamidronate), interleukin-3 and interleukin-6, oral contraceptives, quinidine, rifabutin, streptokinase and sulfonamides. Other systemic medications may cause uveitis. Topical ocular medications such as β-blockers and corticosteroids as well as other topical ocular medications have been associated with uveitis. Cidofovir, pamidronic acid, sulfonamides, rifabutin and topical metipranolol can ‘probably’ cause uveitis. The remainder of the medications discussed have a ‘possible’ cause-and-effect relationship with uveitis.Treatment begins with recognition of a drug-related event and usually subsequent avoidance of the drug. Therapy depends on the severity and likelihood of the reaction. Drug-induced uveitis is almost always reversible within weeks of discontinuation of the drug and treatment of the inflammation.

Update on ethambutol optic neuropathy

Ethambutol optic neuropathy is a well-recognised adverse ocular event in patients who receive ethambutol for the treatment of mycobacterial infections. Much has been published on this condition; however, understanding of patient outcomes and the mechanism by which ethambutol optic neuropathy occurs, as well as data published in textbooks and reference books, tend to lag behind what is currently known. The purpose of this article is to update the clinician on what is currently accepted in regards to the clinical presentation of ethambutol optic neuropathy and what type of eye care should be provided to patients treated with this medication. In addition, new treatment recommendations are suggested to assist clinicians in complying with currently accepted standards of care.

Central serous chorioretinopathy associated with sildenafil.

Purpose: To investigate a suspected relationship between central serous chorioretinopathy (CSC) and sildenafil therapy. Methods: For this retrospective, observational case series, the authors reviewed over 1,500 case reports of sildenafil-associated ocular side effects from the postmarketing surveillance databases of the Food and Drug Administration (FDA), the World Health Organization (WHO), and the National Registry of Drug-Induced Ocular Side Effects. They also performed a Medline literature search for “retinopathy, retinal edema, macular edema” (terms associated with CSC) and “sildenafil.” They identified 11 cases of CSC in men taking sildenafil. Results: In 8 of 11 cases, patients stopped sildenafil therapy when CSC occurred. In 6 of these 8 cases, patients’ vision improved after sildenafil cessation. In 3 cases, effects recurred when patients resumed sildenafil therapy, but stopping therapy was not associated with improvement of CSC in every case. Two patients continued to experience CSC after sildenafil cessation. Conclusion: Practitioners who see patients with refractory CSC should consider recommending cessation of sildenafil therapy; however, because of the cyclic nature of CSC, a causal relationship has not yet been established. Additional possible case reports can be sent to the National Registry of Drug-Induced Ocular Side Effects, the FDA, the WHO, or the manufacturer.

Adverse systemic effects from pledgets of topical ocular phenylephrine 10

PURPOSE To report 11 cases of adverse systemic reactions to topical ocular application of phenylephrine 10% in pledget form and to discourage this method of treatment for hemostasis in laser assisted in-situ keratomileusis (LASIK) surgery and other ophthalmic uses. DESIGN Observational case series. METHODS The literature, reports provided to the spontaneous reporting system of the United States Food and Drug Administration and the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon) were reviewed. Age, sex, duration of therapy, other drugs the patient was taking, and systemic reactions are provided in the series of 11 cases with adverse systemic reactions. RESULTS Eleven cases of adverse systemic reactions to topical ocular phenylephrine 10% applied in pledget form occurred in 8 male and 3 female patients with an age range from 1 to 76 years. All cases occurred after a single exposure, most patients noted systemic effects within minutes of phenylephrine application, and the adverse systemic reactions included severe hypertension, pulmonary edema, cardiac arrhythmia, cardiac arrest, and subarachnoid hemorrhage. CONCLUSIONS We recommend ophthalmologists not use this method of phenylephrine application and believe it is contraindicated in ophthalmic surgery, especially when other medications may be used.