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Barroso F, Crispim Ribeiro J, P. Miranda E. Phosphodiesterase Type 5 Inhibitors and Visual Side Effects: A Narrative Review. JOVR [Internet]. 2021Apr.29 [cited 2024Jul.18];16(2):248–259. Available from: https://knepublishing.com/index.php/JOVR/article/view/9088
https://doi.org/10.18502/jovr.v16i2.9088
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Francisco Barroso
Francisco Barroso
Federal University of Ceara, Fortaleza, Ceara, Brazil
-
João Crispim Ribeiro
João Crispim Ribeiro
Christus University Center, Fortaleza, Ceara, Brazil
-
Eduardo P. Miranda
Eduardo P. Miranda
Federal University of Ceara, Fortaleza, Ceara, Brazil
Published Date
- Apr 29, 2021
Phosphodiesterase Type 5 Inhibitors and Visual Side Effects: A Narrative Review
Abstract
Phosphodiesterase type 5 inhibitors such as sildenafil citrate and tadalafil are well known for the treatment of erectile dysfunction. However, their use in the presence of pulmonary hypertension can cause ophthalmologic side effects, including non-arteritic optic ischemic neuropathy, chorioretinopathy, glaucoma, and optic atrophy. The present review aimed to identify these visual side effects and provide recommendations. We identified articles published from January 2000 to March 2019 on diseases arising from the management of sexual dysfunction in urology or pulmonary hypertension in pneumonia that could cause pathologic alterations in eye structure based on a literature search of the MEDLINE electronic database using keywords for the most common adverse effects and different kinds of phosphodiesterase 5 inhibitors. After applying the exclusion criteria, we selected 36 of the 77 articles initially identified to write the narrative review and added 20 additional articles to completely describe the pathological entities. Phosphodiesterase type 5 inhibitors can cause side effects in the eye including ocular surface abnormalities, increased intraocular pressure and glaucoma, uveitis, non-arteritic ischemic neuropathy, chorioretinopathy, retinal occlusion, and visual field changes. There is an increased need for well-performed studies to better understand these side effects, which are common due to the wide use of sildenafil.
Keywords:
Adverse Effects, Eye Manifestations, Physiological, Review, Sexual Dysfunction, Sildenafil Citrate
References
1. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med 2007;120:151–157.
2. Kehat R, Bonsall DJ, North R, Connors B. Ocular findings of oral sildenafil use in term and near-term neonates. J AAPOS 2010;14:159–162.
3. Sowka JW, Neiberg MN, Vollmer LA. Optic atrophy after sildenafil use. Optometry 2007;78:122–128.
4. Hom MM, Nguyen AL, Bielory L. Allergic conjunctivitis and dry eye syndrome. Ann Allergy Asthma Immunol 2012;108:163–166.
5. Keay L, Stapleton F, Schein O. Epidemiology of contact lens-related inflammation and microbial keratitis: a 20- year perspective. Eye Contact Lens 2007;33:346–353, discussion 62–63.
6. Gupta N, Tandon R, Gupta SK, Sreenivas V, Vashist P. Burden of corneal blindness in India. Indian J Community Med 2013;38:198–206.
7. Nirmalan PK, Katz J, Tielsch JM, Robin AL, Thulasiraj RD, Krishnadas R, et al. Ocular trauma in a rural south Indian population: the Aravind Comprehensive Eye Survey. Ophthalmology 2004;111:1778–1181.
8. Matieli L, Berezovsky A, Salomao SR, Allemann N, Martins EN, Hirai FE, et al. Ocular toxicity assessment of chronic sildenafil therapy for pulmonary arterial hypertension. Graefes Arch Clin Exp Ophthalmol 2016;254:1167–1174.
9. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:75–92.
10. Damar E, Toklu Y, Tuncel A, Balci M, Aslan Y, Simsek S, et al. Does therapeutic dose of sildenafil citrate treatment lead to central serous chorioretinopathy in patients with erectile dysfunction? Am J Mens Health 2013;7:439–443.
11. Turkcu FM, Yuksel H, Sahin A, Murat M, Bozkurt Y, Caca I. Central serous chorioretinopathy due to tadalafil use. Int Ophthalmol 2013;33:177–180.
12. French DD, Margo CE. Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study. Retina 2010;30:271–274.
13. Gordon-Bennett P, Rimmer T. Central serous chorioretinopathy following oral tadalafil. Eye 2012;26:168–169.
14. Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol 2016;100:86–93.
15. Wirostko BM, Tressler C, Hwang LJ, Burgess G, Laties AM. Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double masked, placebo controlled trial and open label extension. BMJ 2012;344:e554.
16. Grunwald JE, Jacob SS, Siu K, Piltz J, Dupont J. Acute effects of sildenafil citrate (Viagra) on intraocular pressure in open-angle glaucoma. Am J Ophthalmol 2001;132:872–874.
17. Lee WJ, Seong M. Sildenafil citrate and choroidal thickness. Retina 2011;31:1742; author reply -3.
18. Garg A, Gazzard G. Selective laser trabeculoplasty: past, present, and future. Eye 2018;32:863–876.
19. Ramasamy B, Rowe F, Nayak H, Peckar C, Noonan C. Acute angle-closure glaucoma following sildenafil citrate-aided sexual intercourse. Acta Ophthalmol Scand 2007;85:229–230.
20. Nazari A, Tabrizi YT, Mokhtaree M. Effect of periodic sildenafil dosage on intraocular pressure in patients with erectile dysfunction. Electron Physician 2017;9:5229–5232.
21. Chen SP, Singh K, Lin SC. Use of phosphodiesterase inhibitors and prevalence of self-reported glaucoma in the United States. PLoS ONE 2017;12:e0183388.
22. Gerometta R, Alvarez LJ, Candia OA. Effect of sildenafil citrate on intraocular pressure and blood pressure in human volunteers. Exp Eye Res 2011;93:103–107.
23. Gerometta R, Alvarez LJ, Candia OA. Effects of sildenafil and tadalafil on intraocular pressure in sheep: implications for aqueous humor dynamics. Invest Ophthalmol Vis Sci 2010;51:3139–3144.
24. Yajima T, Yajima Y, Koppiker N, Grunwald JE, Laties AM. No clinically important effects on intraocular pressure after short-term administration of sildenafil citrate (Viagra). Am J Ophthalmol 2000;129:675–676.
25. Ermis SS, Inan UU, Samli M, Ozturk F. Acute effects of sildenafil on Humphrey visual field and intraocular pressure. Int Ophthalmol 2004;25:69–72.
26. Dundar SO, Dundar M, Kocak I, Dayanir Y, Ozkan SB. Effect of sildenafil on ocular haemodynamics. Eye 2001;15:507–510.
27. Han YS, Rivera-Grana E, Salek S, Rosenbaum JT. Distinguishing uveitis secondary to sarcoidosis from idiopathic disease: cardiac implications. JAMA Ophthalmol 2018;136:109–115.
28. Krishna U, Ajanaku D, Denniston AK, Gkika T. Uveitis: a sight-threatening disease which can impact all systems. Postgrad Med J 2017;93:766–773.
29. Isik M, Kilic L, Dogan I. Recurrent uveitis due to sildenafil usage in a patient with Bechet’s disease. Rheumatol Int 2013;33:803.
30. Su DH, Ang PS, Tow SL. Bilateral posterior ischemic optic neuropathy associated with use of sildenafil. J Neuroophthalmol 2008;28:75.
31. Li A, Li L, Li M, Shi X. A new characterization for nonarteritic anterior ischemic optic neuropathy. Int J Clin Exp Med 2015;8:18681–18688.
32. Boshier A, Pambakian N, Shakir SA. A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil. Int J Clin Pharmacol Ther 2002;40:422– 423.
33. Tripathi A, O’Donnell NP. Branch retinal artery occlusion; another complication of sildenafil. Br J Ophthalmol 2000;84:934–935.
34. Pomeranz HD. Erectile dysfunction agents and nonarteritic anterior ischemic optic neuropathy. Neurol Clin 2017;35:17–27.
35. Coca MN, Morgan ML, Gupta P, Elkeeb A, Lee AG. Bilateral posterior ischemic optic neuropathy associated with the use of Sildenafil for pulmonary hypertension. Can J Ophthalmol 2016;51:e96–e99.
36. Galvez-Ruiz A, Arishi N. Sequential, non-arteritic anterior ischemic optic neuropathy in patients taking sildenafil: a report of ten cases. Saudi J Ophthalmol 2013;27:241–246.
37. Gedik S, Yilmaz G, Akova YA. Sildenafil-associated consecutive nonarteritic anterior ischaemic optic neuropathy, cilioretinal artery occlusion, and central retinal vein occlusion in a haemodialysis patient. Eye 2007;21:129–130.
38. Hafidi Z, Handor H, Laghmari M, Daoudi R. Cilioretinal artery and central retinal vein occlusion after sildenafil use. Emerg Med J 2014;31:535.
39. Pomeranz HD, Smith KH, Hart WM Jr, Egan RA. Sildenafilassociated nonarteritic anterior ischemic optic neuropathy. Ophthalmology 2002;109:584–587.
40. Pomeranz HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (Viagra): a report of seven new cases. J Neuroophthalmol 2005;25:9–13.
41. Oguz H. Sildenafil-associated vascular casualties. Eye 2007;21:676–677; author reply 7–8.
42. Peter NM, Singh MV, Fox PD. Tadalafil-associated anterior ischaemic optic neuropathy. Eye 2005;19:715–717.
43. Pepin S, Pitha-Rowe I. Stepwise decline in visual field after serial sildenafil use. J Neuroophthalmol 2008;28:76–77.
44. Fraunfelder FW, Fraunfelder FT. Central serous chorioretinopathy associated with sildenafil. Retina 2008;28:606–609.
45. Varma D, Lee AW, Chen CS. Reply: ’a review of central retinal artery occlusion: clinical presentation and management’. Eye 2014;28:1270.
46. Rudkin AK, Lee AW, Chen CS. Vascular risk factors for central retinal artery occlusion. Eye 2010;24:678–681.
47. Murthy RK, Perez L, Priluck JC, Grover S, Chalam KV. Acute, bilateral, concurrent central retinal artery occlusion in sickle cell disease after use of tadalafil (Cialis). JAMA Ophthalmol 2013;131:1471–1473.
48. Bertolucci A, Latkany RA, Gentile RC, Rosen RB. Hemiretinal artery occlusion associated with sexual activity and sildenafil citrate (Viagra). Acta Ophthalmol Scand 2003;81:198–200.
49. Pinto LM, Morekar S, Mahashur AA. Central retinal vein occlusion in a patient after being commenced on sildenafil citrate for pulmonary arterial hypertension. Indian J Chest Dis Allied Sci 2009;51:249–251.
50. Li AS, Pomeranz HD. Food and drug administration adverse event reports of retinal vascular occlusions associated with phosphodiesterase type 5 inhibitor use. J Neuroophthalmol 2016;36:480–481.
51. Kinoshita J, Iwata N, Shimoda H, Kimotsuki T, Yasuda M. Sildenafil-induced reversible impairment of rod and cone phototransduction in monkeys. Invest Ophthalmol Vis Sci 2015;56:664–673.
52. Laties AM, Fraunfelder FT. Ocular safety of Viagra, (sildenafil citrate). Trans Am Ophthalmol Soc 1999;97:115– 125; discussion 25–28.
53. Stockman A, Sharpe LT, Tufail A, Kell PD, Ripamonti C, Jeffery G. The effect of sildenafil citrate (Viagra) on visual sensitivity. J Vis 2007;7:4.
54. Farooq MU, Naravetla B, Moore PW, Majid A, Gupta R, Kassab MY. Role of sildenafil in neurological disorders. Clin Neuropharmacol 2008;31:353–362.
55. Sinha S, Pathak-Ray V, Ahluwalia H, Morgan JE. Viagra or what? Eye 2004;18:446–448.
56. Cordell WH, Maturi RK, Costigan TM, Marmor MF, Weleber RG, Coupland SG, et al. Retinal effects of 6 months of daily use of tadalafil or sildenafil. Arch Ophthalmol 2009;127:367–373.
2. Kehat R, Bonsall DJ, North R, Connors B. Ocular findings of oral sildenafil use in term and near-term neonates. J AAPOS 2010;14:159–162.
3. Sowka JW, Neiberg MN, Vollmer LA. Optic atrophy after sildenafil use. Optometry 2007;78:122–128.
4. Hom MM, Nguyen AL, Bielory L. Allergic conjunctivitis and dry eye syndrome. Ann Allergy Asthma Immunol 2012;108:163–166.
5. Keay L, Stapleton F, Schein O. Epidemiology of contact lens-related inflammation and microbial keratitis: a 20- year perspective. Eye Contact Lens 2007;33:346–353, discussion 62–63.
6. Gupta N, Tandon R, Gupta SK, Sreenivas V, Vashist P. Burden of corneal blindness in India. Indian J Community Med 2013;38:198–206.
7. Nirmalan PK, Katz J, Tielsch JM, Robin AL, Thulasiraj RD, Krishnadas R, et al. Ocular trauma in a rural south Indian population: the Aravind Comprehensive Eye Survey. Ophthalmology 2004;111:1778–1181.
8. Matieli L, Berezovsky A, Salomao SR, Allemann N, Martins EN, Hirai FE, et al. Ocular toxicity assessment of chronic sildenafil therapy for pulmonary arterial hypertension. Graefes Arch Clin Exp Ophthalmol 2016;254:1167–1174.
9. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:75–92.
10. Damar E, Toklu Y, Tuncel A, Balci M, Aslan Y, Simsek S, et al. Does therapeutic dose of sildenafil citrate treatment lead to central serous chorioretinopathy in patients with erectile dysfunction? Am J Mens Health 2013;7:439–443.
11. Turkcu FM, Yuksel H, Sahin A, Murat M, Bozkurt Y, Caca I. Central serous chorioretinopathy due to tadalafil use. Int Ophthalmol 2013;33:177–180.
12. French DD, Margo CE. Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study. Retina 2010;30:271–274.
13. Gordon-Bennett P, Rimmer T. Central serous chorioretinopathy following oral tadalafil. Eye 2012;26:168–169.
14. Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol 2016;100:86–93.
15. Wirostko BM, Tressler C, Hwang LJ, Burgess G, Laties AM. Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double masked, placebo controlled trial and open label extension. BMJ 2012;344:e554.
16. Grunwald JE, Jacob SS, Siu K, Piltz J, Dupont J. Acute effects of sildenafil citrate (Viagra) on intraocular pressure in open-angle glaucoma. Am J Ophthalmol 2001;132:872–874.
17. Lee WJ, Seong M. Sildenafil citrate and choroidal thickness. Retina 2011;31:1742; author reply -3.
18. Garg A, Gazzard G. Selective laser trabeculoplasty: past, present, and future. Eye 2018;32:863–876.
19. Ramasamy B, Rowe F, Nayak H, Peckar C, Noonan C. Acute angle-closure glaucoma following sildenafil citrate-aided sexual intercourse. Acta Ophthalmol Scand 2007;85:229–230.
20. Nazari A, Tabrizi YT, Mokhtaree M. Effect of periodic sildenafil dosage on intraocular pressure in patients with erectile dysfunction. Electron Physician 2017;9:5229–5232.
21. Chen SP, Singh K, Lin SC. Use of phosphodiesterase inhibitors and prevalence of self-reported glaucoma in the United States. PLoS ONE 2017;12:e0183388.
22. Gerometta R, Alvarez LJ, Candia OA. Effect of sildenafil citrate on intraocular pressure and blood pressure in human volunteers. Exp Eye Res 2011;93:103–107.
23. Gerometta R, Alvarez LJ, Candia OA. Effects of sildenafil and tadalafil on intraocular pressure in sheep: implications for aqueous humor dynamics. Invest Ophthalmol Vis Sci 2010;51:3139–3144.
24. Yajima T, Yajima Y, Koppiker N, Grunwald JE, Laties AM. No clinically important effects on intraocular pressure after short-term administration of sildenafil citrate (Viagra). Am J Ophthalmol 2000;129:675–676.
25. Ermis SS, Inan UU, Samli M, Ozturk F. Acute effects of sildenafil on Humphrey visual field and intraocular pressure. Int Ophthalmol 2004;25:69–72.
26. Dundar SO, Dundar M, Kocak I, Dayanir Y, Ozkan SB. Effect of sildenafil on ocular haemodynamics. Eye 2001;15:507–510.
27. Han YS, Rivera-Grana E, Salek S, Rosenbaum JT. Distinguishing uveitis secondary to sarcoidosis from idiopathic disease: cardiac implications. JAMA Ophthalmol 2018;136:109–115.
28. Krishna U, Ajanaku D, Denniston AK, Gkika T. Uveitis: a sight-threatening disease which can impact all systems. Postgrad Med J 2017;93:766–773.
29. Isik M, Kilic L, Dogan I. Recurrent uveitis due to sildenafil usage in a patient with Bechet’s disease. Rheumatol Int 2013;33:803.
30. Su DH, Ang PS, Tow SL. Bilateral posterior ischemic optic neuropathy associated with use of sildenafil. J Neuroophthalmol 2008;28:75.
31. Li A, Li L, Li M, Shi X. A new characterization for nonarteritic anterior ischemic optic neuropathy. Int J Clin Exp Med 2015;8:18681–18688.
32. Boshier A, Pambakian N, Shakir SA. A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil. Int J Clin Pharmacol Ther 2002;40:422– 423.
33. Tripathi A, O’Donnell NP. Branch retinal artery occlusion; another complication of sildenafil. Br J Ophthalmol 2000;84:934–935.
34. Pomeranz HD. Erectile dysfunction agents and nonarteritic anterior ischemic optic neuropathy. Neurol Clin 2017;35:17–27.
35. Coca MN, Morgan ML, Gupta P, Elkeeb A, Lee AG. Bilateral posterior ischemic optic neuropathy associated with the use of Sildenafil for pulmonary hypertension. Can J Ophthalmol 2016;51:e96–e99.
36. Galvez-Ruiz A, Arishi N. Sequential, non-arteritic anterior ischemic optic neuropathy in patients taking sildenafil: a report of ten cases. Saudi J Ophthalmol 2013;27:241–246.
37. Gedik S, Yilmaz G, Akova YA. Sildenafil-associated consecutive nonarteritic anterior ischaemic optic neuropathy, cilioretinal artery occlusion, and central retinal vein occlusion in a haemodialysis patient. Eye 2007;21:129–130.
38. Hafidi Z, Handor H, Laghmari M, Daoudi R. Cilioretinal artery and central retinal vein occlusion after sildenafil use. Emerg Med J 2014;31:535.
39. Pomeranz HD, Smith KH, Hart WM Jr, Egan RA. Sildenafilassociated nonarteritic anterior ischemic optic neuropathy. Ophthalmology 2002;109:584–587.
40. Pomeranz HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (Viagra): a report of seven new cases. J Neuroophthalmol 2005;25:9–13.
41. Oguz H. Sildenafil-associated vascular casualties. Eye 2007;21:676–677; author reply 7–8.
42. Peter NM, Singh MV, Fox PD. Tadalafil-associated anterior ischaemic optic neuropathy. Eye 2005;19:715–717.
43. Pepin S, Pitha-Rowe I. Stepwise decline in visual field after serial sildenafil use. J Neuroophthalmol 2008;28:76–77.
44. Fraunfelder FW, Fraunfelder FT. Central serous chorioretinopathy associated with sildenafil. Retina 2008;28:606–609.
45. Varma D, Lee AW, Chen CS. Reply: ’a review of central retinal artery occlusion: clinical presentation and management’. Eye 2014;28:1270.
46. Rudkin AK, Lee AW, Chen CS. Vascular risk factors for central retinal artery occlusion. Eye 2010;24:678–681.
47. Murthy RK, Perez L, Priluck JC, Grover S, Chalam KV. Acute, bilateral, concurrent central retinal artery occlusion in sickle cell disease after use of tadalafil (Cialis). JAMA Ophthalmol 2013;131:1471–1473.
48. Bertolucci A, Latkany RA, Gentile RC, Rosen RB. Hemiretinal artery occlusion associated with sexual activity and sildenafil citrate (Viagra). Acta Ophthalmol Scand 2003;81:198–200.
49. Pinto LM, Morekar S, Mahashur AA. Central retinal vein occlusion in a patient after being commenced on sildenafil citrate for pulmonary arterial hypertension. Indian J Chest Dis Allied Sci 2009;51:249–251.
50. Li AS, Pomeranz HD. Food and drug administration adverse event reports of retinal vascular occlusions associated with phosphodiesterase type 5 inhibitor use. J Neuroophthalmol 2016;36:480–481.
51. Kinoshita J, Iwata N, Shimoda H, Kimotsuki T, Yasuda M. Sildenafil-induced reversible impairment of rod and cone phototransduction in monkeys. Invest Ophthalmol Vis Sci 2015;56:664–673.
52. Laties AM, Fraunfelder FT. Ocular safety of Viagra, (sildenafil citrate). Trans Am Ophthalmol Soc 1999;97:115– 125; discussion 25–28.
53. Stockman A, Sharpe LT, Tufail A, Kell PD, Ripamonti C, Jeffery G. The effect of sildenafil citrate (Viagra) on visual sensitivity. J Vis 2007;7:4.
54. Farooq MU, Naravetla B, Moore PW, Majid A, Gupta R, Kassab MY. Role of sildenafil in neurological disorders. Clin Neuropharmacol 2008;31:353–362.
55. Sinha S, Pathak-Ray V, Ahluwalia H, Morgan JE. Viagra or what? Eye 2004;18:446–448.
56. Cordell WH, Maturi RK, Costigan TM, Marmor MF, Weleber RG, Coupland SG, et al. Retinal effects of 6 months of daily use of tadalafil or sildenafil. Arch Ophthalmol 2009;127:367–373.