Phosphodiesterase inhibitors and the eye

Phosphodiesterase type 5 (PDE5) inhibitors are effective oral treatments for erectile dysfunction and have become one of the most widely prescribed medications worldwide. The mechanism of action is to reduce the degradation of cyclic GMP (cGMP) potentiating the effect of nitric oxide in the corpus cavernosum and allowing erectile function to occur by consequent relaxation of penile smooth muscle. Because of the presence of PDE5 in choroidal and retinal vessels these medications increase choroidal blood flow and cause vasodilation of the retinal vasculature. The most common symptoms are a blue tinge to vision and an increased sensitivity to light. There have been reports of non‐arteritic anterior ischaemic optic neuropathy and serous macular detachment in users of PDE5 inhibitors, although a causal relationship has not been conclusively shown. Despite the role of cGMP in the production and drainage of aqueous humour these medications do not appear to alter intraocular pressure and are safe in patients with glaucoma. All PDE5 inhibitors weakly inhibit PDE6 located in rod and cone photoreceptors resulting in mild and transient visual symptoms that correlate with plasma concentrations. Psychophysical tests reveal no effect on visual acuity, visual fields or contrast sensitivity; however, some studies show a mild and reversible impairment of blue‐green colour discrimination. PDE5 inhibitors transiently alter retinal function on electroretinogram testing but do not appear to be retinotoxic. Despite the role of cyclic nucleotides in tear production there is no detrimental effect on tear film quality. Based on the available evidence PDE5 inhibitors have a good ocular safety profile.

[1]  L. Kuo,et al.  Sildenafil (Viagra) evokes retinal arteriolar dilation: dual pathways via NOS activation and phosphodiesterase inhibition. , 2008, Investigative ophthalmology & visual science.

[2]  C. Foresta,et al.  Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects , 2008, Eye.

[3]  L. Levin,et al.  Erectile dysfunction drugs and risk of anterior ischaemic optic neuropathy: casual or causal association? , 2007, British Journal of Ophthalmology.

[4]  B. Unal,et al.  Effects of vardenafil on intraocular pressure and orbital hemodynamics. , 2007, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[5]  P. Szurman,et al.  The effects of the phosphodiesterase type V inhibitor sildenafil on human and bovine retinal function in vitro , 2007, Graefe's Archive for Clinical and Experimental Ophthalmology.

[6]  C. Supuran,et al.  Phosphodiesterase 5 inhibitors--drug design and differentiation based on selectivity, pharmacokinetic and efficacy profiles. , 2006, Current pharmaceutical design.

[7]  İ. Koçak,et al.  Effects of sildenafil on blue-on-yellow and white-on-white Humphrey perimetry in 3 months regular use , 2006, Eye.

[8]  G. Ying,et al.  Effect of viagra on retinal vein diameter in AMD patients. , 2006, Experimental eye research.

[9]  İ. Koçak,et al.  Effect of sildenafil on ocular hemodynamics in 3 months regular use , 2006, International Journal of Impotence Research.

[10]  L. Gorkin,et al.  Sildenafil citrate use and the incidence of nonarteritic anterior ischemic optic neuropathy , 2006, International journal of clinical practice.

[11]  T. Welte,et al.  Sildenafil citrate therapy for pulmonary arterial hypertension. , 2006, The New England journal of medicine.

[12]  H. Oğuz,et al.  Ophthalmic aspects of erectile dysfunction drugs. , 2006, American journal of ophthalmology.

[13]  W. Seeger,et al.  Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension , 2006, Cerebrovascular Diseases.

[14]  A. Akıncı,et al.  Sildenafil Associated Pupil-Sparing Third Nerve Palsy , 2006 .

[15]  C. Page,et al.  Phosphodiesterase inhibitors , 2006, British journal of pharmacology.

[16]  H. Oğuz,et al.  The acute effects of sildenafil on tear functions , 2005 .

[17]  T. Fleming,et al.  Sildenafil citrate therapy for pulmonary arterial hypertension. , 2005, The New England journal of medicine.

[18]  N. Alpert,et al.  Effects of sildenafil on myocardial blood flow in humans with ischemic heart disease , 2005, Coronary artery disease.

[19]  J. Hescheler,et al.  Effects of phosphodiesterase type 5 inhibitor sildenafil on retinal function in isolated superfused retina. , 2005, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[20]  H. Oğuz,et al.  No effects of long-term sildenafil treatment on ocular functions , 2005 .

[21]  Ç. Yeşilli,et al.  The effects of sildenafil on ocular blood flow. , 2005, Acta ophthalmologica Scandinavica.

[22]  R. Egan,et al.  Visual field defect and intracerebral hemorrhage associated with use of vardenafil (Levitra) , 2005, Neurology.

[23]  D. Sarraf,et al.  Viagra-associated serous macular detachment , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[24]  Tolga Uçar,et al.  Effect of Sildenafil Citrate on Retinal Functions: Preliminary Report on Humphrey Visual Field Analysis , 2004, Urologia Internationalis.

[25]  E. Bischoff Potency, selectivity, and consequences of nonselectivity of PDE inhibition , 2004, International Journal of Impotence Research.

[26]  A. Rilk,et al.  Visual short-term effects of Viagra: double-blind study in healthy young subjects. , 2004, American journal of ophthalmology.

[27]  J. Gale,et al.  Central serous chorioretinopathy in a patient taking sildenafil citrate. , 2004, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.

[28]  F. Ozturk,et al.  Acute Effects of Sildenafil on Humphrey Visual Field and Intraocular Pressure , 2004, International Ophthalmology.

[29]  W. Sponsel,et al.  Sildenafil increases ocular perfusion , 2004, International Ophthalmology.

[30]  İ. Koçak,et al.  Evaluation of side effects of sildenafil in group of young healthy volunteers , 2004, International Urology and Nephrology.

[31]  L. Schmetterer,et al.  Effects of sildenafil on retinal blood flow and flicker-induced retinal vasodilatation in healthy subjects. , 2003, Investigative ophthalmology & visual science.

[32]  O. Kayikcioglu,et al.  Histopathologic effect of chronic use of sildenafil citrate on the choroid & retina in male rats. , 2003, The Indian journal of medical research.

[33]  M. Marmor,et al.  Effects of Sildenafil Citrate (Viagra) on Choroidal Congestion , 2002, Ophthalmologica.

[34]  J. Grunwald,et al.  Effect of sildenafil citrate (Viagra) on retinal blood vessel diameter. , 2002, American journal of ophthalmology.

[35]  W. Swanson,et al.  A double-blind placebo-controlled evaluation of the acute effects of sildenafil citrate (Viagra) on visual function in subjects with early-stage age-related macular degeneration. , 2002, American journal of ophthalmology.

[36]  S. Orgül,et al.  Sildenafil induces retinal vasodilatation in healthy subjects , 2002, The British journal of ophthalmology.

[37]  J. Grunwald,et al.  Acute effects of sldenafil ctrate (Viagra) on intraocular pressure in open-angle glaucoma. , 2001, American journal of ophthalmology.

[38]  J. Morgan,et al.  Transient ischemic attack and stroke associated with sildenafil (Viagra) use , 2001, Neurology.

[39]  M. Marmor,et al.  Acute effects of sildenafil on the electroretinogram and multifocal electroretinogram. , 2001, American journal of ophthalmology.

[40]  İ. Koçak,et al.  Effect of sildenafil on ocular haemodynamics , 2001, Eye.

[41]  J. Grunwald,et al.  Effect of sildenafil citrate (Viagra) on the ocular circulation. , 2001, American journal of ophthalmology.

[42]  A. Fabbri,et al.  Subjective visual halos after sildenafil (Viagra) administration: Electroretinographic evaluation. , 2001, Ophthalmology.

[43]  W. Klaus,et al.  Modulation of Human Platelet Aggregation by the Phosphodiesterase Type 5 Inhibitor Sildenafil , 2001, Journal of cardiovascular pharmacology.

[44]  R. Monastero,et al.  Intracerebral haemorrhage associated with sildenafil citrate , 2001, Journal of Neurology.

[45]  N. Buxton,et al.  Sildenafil (Viagra)-induced spontaneous intracerebral haemorrhage. , 2001, British journal of neurosurgery.

[46]  Byron L. Lam,et al.  Acute Effects of Sildenafil (Viagra) on Blue‐on‐Yellow and White‐on‐White Humphrey Perimetry , 2000, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.

[47]  W. Sponsel,et al.  Sildenafil and ocular perfusion. , 2000, The New England journal of medicine.

[48]  A. Laties,et al.  No clinically important effects on intraocular pressure after short-term administration of sildenafil citrate (Viagra). , 2000, American journal of ophthalmology.

[49]  W. Green,et al.  Histopathologic studies of ischemic optic neuropathy. , 2000, Transactions of the American Ophthalmological Society.

[50]  I. Goldstein,et al.  Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. , 1998, The New England journal of medicine.

[51]  M. Marmor,et al.  Sildenafil (Viagra) and ophthalmology. , 1999, Survey of ophthalmology.

[52]  F. J. Rocha,et al.  Androgens and Dry Eye in Sjögren's Syndrome a , 1999, Annals of the New York Academy of Sciences.

[53]  I. Osterloh,et al.  Overall cardiovascular profile of sildenafil citrate. , 1999, The American journal of cardiology.

[54]  K. Bartz-Schmidt,et al.  Retinal side-effects of sildenafil , 1999, The Lancet.

[55]  A. Laties,et al.  Ocular safety of Viagra, (sildenafil citrate). , 1999, Transactions of the American Ophthalmological Society.

[56]  S. Donahue,et al.  Pupil-sparing third nerve palsy associated with sildenafil citrate (Viagra). , 1998, American journal of ophthalmology.

[57]  Tom F. Lue,et al.  Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. , 1998, New England Journal of Medicine.

[58]  A. Sato,et al.  Cilostazol, a selective cAMP phosphodiesterase inhibitor, dilates retinal arterioles and increases retinal and choroidal blood flow in rats. , 1998, European journal of pharmacology.

[59]  S. Jacobson,et al.  Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. , 1995, Genomics.

[60]  J. Beavo,et al.  Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. , 1995, Physiological reviews.

[61]  P. Kaufman,et al.  Effect of 8-Br cGMP on aqueous humor dynamics in monkeys. , 1994, Investigative ophthalmology & visual science.

[62]  L. Ignarro,et al.  Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. , 1992, The New England journal of medicine.

[63]  B. Becker Topical 8-bromo-cyclic GMP lowers intraocular pressure in rabbits. , 1990, Investigative ophthalmology & visual science.

[64]  Scott Nawy,et al.  Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells , 1990, Nature.

[65]  M. Pornin,et al.  [Phosphodiesterase inhibitors]. , 1990, Annales de cardiologie et d'angeiologie.

[66]  R. Beck,et al.  Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. , 1987 .

[67]  E. Kohner,et al.  Role of axoplasmic transport in the pathophysiology of ischaemic disc swelling. , 1980, British Journal of Ophthalmology.

[68]  P. Hamet,et al.  Cyclic GMP binding and cyclic GMP phosphodiesterase in rat platelets. , 1978, Journal of cyclic nucleotide research.

[69]  D. Farber,et al.  Cyclic Guanosine Monophosphate: Elevation in Degenerating Photoreceptor Cells of the C3H Mouse Retina , 1974, Science.

[70]  P. Lundberg,et al.  HE BENIGN AND MALIGNANT FORMS OF ORGASMIC CEPHALGIA , 1974, Headache.

[71]  J. Beavo,et al.  Hydrolysis of cyclic guanosine and adenosine 3',5'-monophosphates by rat and bovine tissues. , 1970, The Journal of biological chemistry.