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Case Report
Central Retinal Vein Occlusion in a Patient After Being
Commenced on Sildenafil Citrate for Pulmonary Arterial
Hypertension
Lancelot M. Pinto, Sunil Morekar and Ashok A. Mahashur
Department of Pulmonology, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai(Maharashtra), India ABSTRACT
A 75-year-old female was commenced on sildenafil for the treatment of pulmonary arterial hypertension (PAH) secondary
to chronic obstructive pulmonary disease (COPD). She reported blurring of vision within 72 hours after starting treatment
and was found to have a central retinal vein occlusion (CRVO). Such an occurrence is the second case reported to date, and
we review the possible mechanisms and literature on the subject. [Indian J Chest Dis Allied Sci 2009;51:249-251]
Key words: Sildenafil, Central retinal vein occlusion.
INTRODUCTION
the airflow obstruction after the administration of abronchodilator, and she was diagnosed to havesevere COPD (GOLD Stage III). She was a non-smoker, Pulmonary arterial hypertension (PAH) is one of the but was exposed in the past to biomass fuels used in known and distressing sequelae of chronic cooking. In 2003, her arterial blood gas (ABG) obstructive pulmonary disease (COPD). The thera- analysis performed at a regular follow-up revealed a peutic options for the treatment of PAH are limited.
arterial oxygen tension (PaO ) of 50mmHg, and she Sildenafil citrate, a selective phosphodiesterase-5 was prescribed long-term oxygen therapy. In addition inhibitor and partial phosphodiesterase-6 inhibitor has shown significant results in the treatment of ipratropium and β -agonists, she was on oral idiopathic pulmonary arterial hypertension, and its prednisolone at a dose of 10mg per day since two use has been extended to pulmonary hypertension years; frequent attempts at reducing this dose had secondary to underlying lung disease, with resulted in worsening of breathlessness. She was a promising results. However, its use has been known hypertensive, diagnosed in 2003 and was on associated with ocular adverse effects, and caution oral losartan (50mg once a day) with a good control of needs to be exercised in prescribing the drug.
her blood pressure achieved with the dose. She was Educating patients to be vigilant in promptly detected to have diabetes mellitus a month prior to recognising and reporting these adverse effects is of admission, possibly secondary to her being prescribed oral corticosteroids on a long-term basis.
She was on oral metformin 500mg twice a day with a CASE REPORT
satisfactory glycaemic control. The last echocardio-graphy done prior to the admission in March 2005 A 75-year-old female was hospitalised in July 2006 had revealed a dilatation of the right atrium and right with breathlessness at rest which had progressively ventricle, with a pulmonary arterial systolic pressure worsened in the month prior to admission.
(PASP) of 66mmHg and mean pulmonary arterial A pulmonary function testing performed in 2001 had revealed forced expiratory volume in the first second (FEV ) to forced vital capacity (FVC) ratio of suggestive of type I respiratory failure, PaO of 53 0.54 with FEV being 41.2% of the normal value mmHg, fraction of inspired oxygen (FiO ) of 0.35. Her predicted. There was no significant reversibility of laboratory investigations were notable for mild [Received: March 14, 2008; accepted after revision: February 19, 2009]
Correspondence and reprint requests: Dr A.A. Mahashur, Department of Pulmonology, P.D. Hinduja National Hospital and
Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400 016 (Maharashtra), India; Phone: 91-22-24447272; E-mail:
[email protected]
Ocular Adverse Effects of Sildenafil for Treating PAH
L.M. Pinto et al
polycythaemia (haemoglobin 15.3g/dL, haematocrit DISCUSSION
47%). Total white cell count was 6300/mm3 and thechest radiograph revealed hyperinflated lung fields Sildenafil citrate causes vascular smooth muscle with no localised pathology. Routine blood relaxation, by altering the cyclic guanosine biochemistry revealed normal liver and renal monophosphate (cGMP) pathway. The cGMP, though functions. A 12-lead electrocardiogram was notable a cascade of reactions, decreases intracellular for a right-axis deviation with P-pulmonale. In the calcium, causing smooth muscle relaxation. The absence of any overt evidence of an infective cGMP is enzymatically degraded by phospho- exacerbation, a transthoracic 2-dimensional diesterases within the cell, and thus, inhibition of echocardiography was performed. It was notable for these enzymes promtes smooth muscle vasodilation.
worsening of the PASP to 81mmHg (mPAP 45mmHg) Sildenafil citrate selectively inhibits phospho- while on 2 L/min of oxygen via nasal prongs diesterase-5 and partially inhibits phosphodies- (parallel oxygen saturation 95% by pulse oximetry), terase-6, phosphodiesterase-5 being present in the 86mmHg (mPAP 47mmHg) while on one liter per smooth muscle of blood vessels and platelets. This minute (saturation 80%), and 91mmHg (mPAP property of the drug has been used for the treatment of erectile dysfunction; millions of people worldwide compression venous Doppler ultrasonography of both upper and lower limbs was performed, which Its action on causing smooth muscle relaxation ruled out the possibility of a deep vein thrombosis, has extended its use to the treatment of PAH. The and a ventilation-perfusion scan (V/Q scan) revealed SUPER-1 trial proved that in patients with PAH matched ventilation-perfusion defects compatible (either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to- Sildenafil citrate was added to her regular pulmonary shunts) treated with sildenafil citrate, medications at a dose of 25 mg thrice a day. Within 72 there was a significant reduction of pulmonary hours of starting sildenafil, she reported blurring of arterial pressure (PAP), pulmonary vascular vision in the right eye, and the drug was stopped resistance (PVR), improvement in six-minute walk immediately. An ophthalmic evaluation revealed distance and World Health Organization (WHO) normal ocular pressures with an ischemic CRVO in functional class.1 Recent studies2,3 have shown the right eye (Figure). A carotid and a jugular vein promising results with sildenafil in the treatment of Doppler performed to rule out an underlying PAH secondary to underlying lung disease, like atheroembolic disease were normal, and blood Sildenafil has been known to cause ocular side- hypercoagulable/atherogenic state at her age (S.
effects such as altered colour hue or brightness homocysteine, lipid profile) were normal.
perception via its inhibitory actions onphosphodiesterase-6 in the retinal photoreceptors.4Fourteen cases of non-arteritic anterior ischemic opticneuropathy (NAION) associated with sildenafil usehave been reported.5-11 It is hypothesised that reducedperfusion at the optic nerve head secondary to thesystemic hypotension caused by the drug isresponsible for the occurrence of NAION. This theoryis supported by the finding that the incidence ofNAION after sildenafil use may be more inindividuals with underlying vascular diseasesecondary to diabetes, hypertension and heartdisease. It has also been found to be more in patientwith anatomical characteristics such as small cup-to-disc ratios.5 The development of CRVO after ingestion of sildenafil has been reported once in the literature.9The case that was reported involved a 36-year-old Figure. Fundus photograph of the patient's right eye
male with chronic renal failure who developed revealing central retinal vein occlusion.
sudden onset blurring of vision in his left eye afteringestion of sildenafil 100mg for the first time the She remained disease-free in the other eye for night before. Fluorescein angiographic examination almost a year since stopping the drug, although her indicated occlusion of the cilioretinal artery with vision in the affected eye has not improved.
occlusion of the central retinal vein. Despite being 2009;Vol.51
The Indian Journal of Chest Diseases & Allied Sciences
warned not to do so, the patient consumed 100 mg Madden BP, Allenby M, Loke TK, Sheth A. A potential role sildenafil four months later and presented with the for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease.
Vascul Pharmacol 2006;44:372-6.
The association between sildenafil consumption Madden BP, Sheth A, Wilde M, Ong YE. Does sildenafil and CRVO being seldom described, the pathogenesis produce a sustained benefit in patients with pulmonary is not known. Presumably the mechanism is similar hypertension associated with parenchymal lung and to that causing NAION. While our patient did have cardiac disease? Vascul Pharmacol 2007;47:184-8.
risk factors for vascular disease, the normal carotid Centre for Drug Evaluation and Research. A double-blind,randomized, placebo-controlled, four-period crossover artery Doppler, the lack of evidence of any other study to assess the effect of orally administered sildenafil manifestations of vascular disease, the lack of other (50, 100, and 200 mg) on visual function in healthy mail blood biochemical markers of hyper-coagulability, volunteers: study 148-223 Viagra (Sildenafil). Joint Clinical and the temporal sequence of developing CRVO Review for NDA-20-895. Washington DC: Food and Drug within 72 hours of initiating treatment with Pomeranz HD, Smith KH, Hart WM Jr, Egan RA.
sildenafil, makes it a strong possibility that the drug Sildenafil-associated nonarteritic anterior ischemic optic was responsible for her developing the CRVO.
neuropathy. Ophthalmology 2002;109:584-7.
Further, studies would be needed to prove such an Egan RA, Pomeranz HD. Sildenafil (Viagra) associated association, and vigilance on the part of physicians anterior ischemic optic neuropathy. Arch Ophthalmol prescribing the drug can lead to increased reporting Cunningham AV, Smith KH. Anterior ischemic opticneuropathy associated with Viagra. J Neuroophthalmol In conclusion, use of sildenafil citrate in respiratory medicine has increased significantly over Dheer S, Rekhi GS, Merlyn S. Sildenafil associated anterior the past few years. It is a vital drug in the manage- ischemic optic neuropathy. J Assoc Physicians India ment of PAH but pulmonologists and patients need to be aware of its ocular adverse effects. Caution needs Boshier A, Pambakian N, Shakir SA. A case of nonarteriticischemic optic neuropathy (NAION) in a male patient to be exercised in prescribing the drug, especially in taking sildenafil. Int J Pharmacol Ther 2002;40:422-3.
patients with underlying cardiovascular disease, and 10. Howard DP, Abdhish RB. Nonarteritic ischemic optic reporting of adverse effects must be encouraged.
neuropathy developing soon after use of sildenafil(Viagra): a report of seven new cases. J Neuro-Ophthalmol2005;25:9-13.
REFERENCES
11. Gedik S, Yilmaz G, Akova YA. Sildenafil-associated consecutive nonarteritic anterior ischaemic optic Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, neuropathy, cilioretinal artery occlusion, and central retinal Badesch D, et al. Sildenafil citrate therapy for pulmonary vein occlusion in a haemodialysis patient. Eye arterial hypertension. N Engl J Med 2005;353:2148-57.
The Indian Journal of Chest Diseases & Allied Sciences
2009;Vol.51

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