Ophthalmic adverse drug reactions to systemic drugs: a systematic review.
OBJECTIVE
To perform a comprehensive and systematic review regarding ophthalmic adverse drug reactions (ADRs) to systemic drugs to: (i) systematically summarize existing evidence, (ii) identify areas, ophthalmic ADRs or drugs that lacked systematization or assessment (namely drugs with original studies characterizing specific ophthalmic ADRs but without causality assessment nor without meta-analysis).


METHODS
Systematic review of several electronic databases (last search 1/7/2012): Medline, SCOPUS, ISI web of knowledge, ISI Conference Proceedings, International Pharmaceutical Abstracts and Google scholar. Search query included: eye, ocular, ophthalmic, ophthalmology, adverse and reaction. Inclusion criteria were: (i) Primary purpose was to assess an ophthalmic ADR to a systemic medication; (ii) Patient evaluation performed by an ophthalmologist; (iii) Studies that specified diagnostic criteria for an ocular ADR. Different types of studies were included and analyzed separately. Two independent reviewers assessed eligibility criteria, extracted data and evaluated risk of bias.


RESULTS
From 562 studies found, 32 were included (1 systematic review to sildenafil, 11 narrative reviews, 1 trial, 1 prospective study, 6 transversal studies, 6 spontaneous reports and 6 case series). Drugs frequently involved included amiodarone, sildenafil, hydroxychloroquine and biphosphonates. Frequent ophthalmic ADRs included: keratopathy, dry eye and retinopathy.


CONCLUSIONS
To increase evidence about ophthalmic ADRs, there is a need for performing specific systematic reviews, applying strictly the World Health Organization's (WHO) definition of ADR and WHO causality assessment of ADRs. Some ophthalmic ADRs may be frequent, but require ophthalmological examination; therefore, ophthalmologists' education and protocols of collaboration between other specialties whenever they prescribe high-risk drugs are suggestions for the future.
Center for Research in Health Technologies and Information Systems (CINTESIS) and Department of Health Information and Decision Sciences, Faculty of Medicine, University of Porto, Portugal; Department of Ophthalmology, Central University Hospital of Coimbra, Coimbra, Portugal.
Ana
A
Miguel
Filipe
F
Henriques
Luís Filipe
LF
Azevedo
Altamiro Costa
AC
Pereira
D000818:Animals; D002220:Carbamazepine / Q000009:adverse effects; D004164:Diphosphonates / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology*; D005128:Eye Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D010879:Piperazines / Q000009:adverse effects; D011687:Purines / Q000009:adverse effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects
D004164:Diphosphonates; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D002220:Carbamazepine; D000068677:Sildenafil Citrate
adverse drug reactions; clinical pharmacology; ophthalmology; pharmacoepidemiology