High dose sildenafil citrate induced persistent binocular anomalopia: A case report

Background: When taking the recommended dose of sildenafil citrate for male erectile dysfunction (ED) and pulmonary hypertension (PAH), the incidence of ocular side effects, including a sense of blue-tinted vision and changes in brightness perception in the form of increased sensitivity to light, was 0.1–11%, and the visual symptoms were almost transient. Only a few cases reported the large dose of sildenafil citrate. The visual symptoms of these cases were all reversible. Up to now, no case was reported that the visual symptoms was irreversible, except this one. Case Presentation: A 39-year-old man was sent to emergency department for taking over dosage of 800mg sildenafil citrate (trade name Viagra) to commit suicide. Visual symptoms appeared 4 hours later, including photophobia, blue halo in center field and gray stripes over red background. Sildenafil citrate toxicity caused the damage to outer layer of retina, including of myoid zone, ellipsoidal zone and interdigitation zone on OCT. Pattern visual evoked potential (P-VEP) demonstrated that the amplitudes of bilateral 1 degree spatial frequency P100 was declined mildly, and full-field electroretinogram (ERG) showed slightly-reduced amplitudes of dark-adapted ERG b-wave in both eyes. The patient was diagnosed as bilateral drug toxic retinopathy and ametropia. He was treated with compound anisodine hydrobromide. At 3-week follow-up, myoid zone, ellipsoidal zone and interdigitation zone of macular was improved on OCT, the amplitude of bilateral 1 degree spatial frequency P100 and dark-adapted ERG b-wave was improved slightly, but still remained abnormal. However, the visual symptoms did not improve any more over more than 1 year. Conclusions: High dose of sildenafil may lead to irreversible death of the photoreceptor cells and permanent visual impairment. The ocular side effects of recommended dose and potential visual risks of drug overdose should be paid more attention. citrate acts as a phosphodiesterase (PDE) inhibitor. PDE-5 has been demonstrated to be present in bipolar cells, ganglion cells and the endothelial and smooth muscle cells of the vascular wall in retinal and choroidal vessels[1]. PDE-6 is a key isoenzyme located in the outer segments of rods and cones for the conversion of light stimulation to electrical signals[2]. The relative selectivity of sildenafil for PDE-5 was10 times of PDE-6[3].


Background
Sildenafil citrate acts as a phosphodiesterase (PDE) inhibitor. PDE-5 has been demonstrated to be present in bipolar cells, ganglion cells and the endothelial and smooth muscle cells of the vascular wall in retinal and choroidal vessels [1]. PDE-6 is a key isoenzyme located in the outer segments of rods and cones for the conversion of light stimulation to electrical signals [2]. The relative selectivity of sildenafil for PDE-5 was10 times of PDE-6 [3].
When taking the recommended dose of sildenafil citrate for male erectile dysfunction (ED) and pulmonary hypertension (PAH), the incidence of ocular side effects, including a sense of blue-tinted vision and changes in brightness perception in the form of increased sensitivity to light, was 0.1-11% [4][5][6][7], and the visual symptoms were almost transient.
Only a few cases reported the large dose of sildenafil citrate. The visual symptoms of these cases were all reversible.

Case Presentation
A 39-year-old male patient presented to our eye hospital with complaint of binocular anomalopia over 1 week. He took 800mg (50mg×16 tablets) sildenafil citrate (trade name Viagra) which was bought on the internet, attempting to commit suicide for pressure 1 week ago. Visual symptoms appeared 4 hours later, including photophobia, blue halo in center field, gray stripes over red background, accompanied with dizziness and nausea, without vomiting and vision loss. The patient was physically healthy with no noteworthy medical history. Six hours after taking the medicine, the patient was sent to the emergency department of the second affiliated hospital of Wenzhou Medical University.
After blood tests (i.e. blood count, liver and kidney function, and coagulation) and Magnetic Resonance Imaging (MRI), he was diagnosed as drug poisoning and treated with liver protection. The attending doctor then referred the patient to our hospital for his visual complaints.
Ophthalmic examination revealed his best corrected vision acuity(BCVA) was 1.0 in both eyes. Color vision examination showed anerythrochloropsia. There were no afferent pupillary defects and no apparent pathological changes in the anterior segment of either eye. Intraocular pressure was 9.9mmHg in the right eye and 11.8mmHg in the left eye. degree spatial frequency P100 and dark-adapted ERG b-wave was improved slightly, but still remained abnormal at 3-week follow-up ( figure 3C, figure 4B). However, the symptom of binocular anomalopia persists over the following 1 year.

Discussion And Conclusions
When taking the recommended dose ranging of 25 to 100mg/day for male ED and 20 mg three times a day for PAH [8], the incidence of ocular side effects, including a sense of blue-tinted vision and changes in brightness perception in the form of increased sensitivity to light, was 0.1-11% [4][5][6][7].There was a reduction in a-wave, b-wave amplitude and sensitivity of S-cone [9,10], and a prolongation of the photopic a-wave and scotopic bwave [11].The visual symptoms and ERG changes were almost transient [3,12], which were at peak periods in 1~2 hours and disappeared in 3~24 hours after taking sildenafil [9,13].
Concerning the large dose of the drug usage, there were less reported studies and cases.Vision symptoms occurs in 40~50% individuals when taking over a dose of 100 mg sildenafil, 50% individuals using 200mg, and 100% individuals using 600-800mg [21].
Kimet et al reported a case that a patient took 750 mg sildenafil presented blurred vision, OCT demonstrated irregularities in the photoreceptor line, his full-field and multifocal ERG were reduced in amplitudes.The toxicity of sildenafil persisted over several months in the ERG and OCT, these changes returned to normal 1 year later [22]. Izadi et al reported a patient took 1500mg dosage of sildenafil persisted the symptoms of central visual blurring and chromatopsia for 5 months, then returned to normal [23].
In our case, the patient who took 800mg sildenafil was under medical attention immediately, but his visual symptoms still existed 4 hours later.The symptoms of 6 anomalopia and photaesthesia, and the changes of macular outer layer in OCT, were consistent with previous studies.However, the visual symptoms did not improve any more at more than 1 year. It was speculated that a higher dose of sildenafil may lead to irreversible death of the photoreceptor cells and permanent visual impairment, which differs from the previous cases of reversible vision change.
With the increasing number of sildenafil users in China, the ocular side effects of The patient has read and signed the statement of the informed consent. We have obtained consent to publish from the patient to report his data including detailed medical history and clinical examination images. A copy of the written consent is available for review by the Editor of BMC Ophthalmology.
Availability of data and material: All data generated or analyzed during this study are included in this published article.

Competing interests:
The authors declare that they have no competing interests.

Funding:
No funding was obtained for this study.

Authors' contributions
Ying Huang has made the conception of the manuscript, has contributed to analysis and interpretation of data and has been involved in drafting, writing and revising the manuscript. Changbiao Xu has contributed to analysis and interpretation of data and has been involved in drafting the manuscript. Qianqian Zhu performed the OCT, FFA, ERG,VEP examination of the patient. Yikui Zhang has been involved in revising the manuscript.Bing Lin was the attending physician and responsible for the treatment and follow-up of the patient,has made the conception of the manuscript, has been involved in drafting and revising the manuscript and given the final approval of the version to be published.All authors read and approved the final manuscript. Supplementary Files This is a list of supplementary files associated with the primary manuscript. Click to download. CAREchecklist.docx