Ocular toxicity assessment of chronic sildenafil therapy for pulmonary arterial hypertension.
OBJECTIVE
The aim of this study was to investigate possible functional and structural ocular changes caused by chronic sildenafil therapy to treat pulmonary arterial hypertension (PAH).


METHODS
Case-control study included patients with pulmonary arterial hypertension: chronically using sildenafil and without sildenafil treatment. A comprehensive ophthalmologic exam including ectoscopy, extrinsic ocular motility, logMAR visual acuity measurement, contrast sensitivity test, color test, anterior segment biomicroscopy, Schirmer test 1, intraocular pressure, fundus exam under pupil dilation, fundus pictures, time domain and spectral domain optical coherence tomography, ocular Doppler ultrasound were performed. Full-field electroretinography (ERG) was tested for each eye in a subgroup of sildenafil-treated patients.


RESULTS
Twenty patients from each group were tested. Bilateral severe keratitis was found in seven (35 %) patients under sildenafil therapy. Lacrimal film break-up time (BUT) was significantly reduced (p = 0.006 respectively) and Doppler ultrasound showed a reduced resistance index of the central retinal artery in the group of sildenafil users (p = 0.019). No diffuse retinal functional abnormalities were found in ERG in treated patients. Visual acuity, contrast sensitivity and color discrimination were normal in both groups. No abnormalities were found in both time-domain and spectral-domain OCT for retinal parameters.


CONCLUSIONS
One-third of the treated PAH group showed severe bilateral keratitis. This finding could be related to connective tissue abnormalities usually present in patients with this condition that might be exacerbated with the sildenafil usage. The resistance index of the central retinal artery was diminished in the chronic users group and it could be associated to the vasodilation caused by the medication in the choroidal vessels. An ophthalmic assessment for these patients is recommended to diagnose and treat possible ocular surface and choroidal blood flow abnormalities caused by sildenafil.
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil. liciamatieli@gmail.com.
Licia
L
Matieli
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Adriana
A
Berezovsky
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Solange Rios
SR
Salomão
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Norma
N
Allemann
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Elisabeth Nogueira
EN
Martins
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Flavio E
FE
Hirai
Divisão de Pneumologia, Departamento de Clínica Médica, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, São Paulo, SP, Brasil.
Jaquelina
J
Ota-Arakaki
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Maira S A
MS
Morales
Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP, Hospital São Paulo, Rua Botucatu, 822 - Vila Clementino, São Paulo, 04023-062, SP, Brasil.
Denise
D
de Freitas
D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D016022:Case-Control Studies; D004596:Electroretinography; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007634:Keratitis / Q000139:chemically induced* / Q000175:diagnosis; D007766:Lacrimal Apparatus Diseases / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000633:toxicity*; D012161:Retinal Artery / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000503:physiopathology; D000068677:Sildenafil Citrate / Q000633:toxicity*; D018615:Ultrasonography, Doppler, Color; D014792:Visual Acuity
D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
Eye; Keratitis; Pulmonary Hypertension; Sildenafil; Toxicity