| OCR Text |
Show Journal of'A'euro- Ophthalmology 20( 4): 227- 228, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Acute Effects of Sildenafil ( Viagra) on Blue- on- Yellow and White- on- White Humphrey Perimetry Timothy J. McCulley, MD, Byron L. Lam, MD, Michael F. Marmor, MD, Kara B. Hoffman, MD, James K. Luu, MD, and William J. Feuer, MS Objective: To study the effects of sildenafil on blue- on- yellow and white- on- white Humphrey visual field ( HVF). Materials and Methods: Healthy subjects, ages 20 to 38 years, were prospectively randomized to active drug ( n = 5) or placebo ( n = 3) groups. Blue- on- yellow and white- on- white HVF testing was performed before and 1 hour after masked dosing of sildenafil 200 mg or placebo. Changes in mean deviation ( MD) were compared between groups. Results: Three of three placebo and four of five sildenafil subjects had no change on HVF. One of five sildenafil subjects had a decrease in MD of 17.9 dB and 4.7 dB on blue- on- yellow and white- on- white HVF testing, respectively. This subject reported more systemic side effects than other subjects. Conclusions: Sildenafil has no effect on HVF testing in most persons; however, sildenafil caused an acute abnormality of HVF testing in one subject, who experienced pronounced non-visual systemic symptoms; this effect was greater on blue- on-yellow than white- on- white HVF. Key Words: Humphrey visual field- Ophthalmology- Side effects- Sildenafil- Viagra. Sildenafil ( Viagra, Pfizer, New York, NY), a selective phosphodiesterase 5 ( PDE5) inhibitor, has a 10% cross Manuscript received May 17, 2000; accepted July 25, 2000. From the Bascom Palmer Eye Institute ( TM, BL, KH, WF), University of Miami, Florida; and the Department of Ophthalmology ( MM, JL), Stanford University, California. Address correspondence to Byron L. Lam, MD, 900 NW 17th Street, Miami, FL 33136. activity on PDE6, which is involved in phototransduction in retinal photoreceptors ( 1- 3). Some individuals report bluish vision, increased light sensitivity, or diminished color perception, lasting up to hours after ingestion of sildenafil ( 4). A lack of acute changes in white- on- white Humphrey visual field ( HVF) testing has been reported ( 5), and no long- term visual symptoms or dysfunction have been found. This study evaluates effects of sildenafil on blue- on- yellow and white- on- white HVF testing. METHODS After obtaining institution- reviewed informed consent, eight healthy subjects were prospectively randomized, based on the order in which they volunteered, and received active drug ( n = 5, 4 women and 1 man, ages 20- 38 years) or placebo ( n = 3, 3 women, ages 21- 28 years). Subjects were blind to which pill they received. The large percentage of women occurred because more women volunteered. Both eyes of each subject were tested with white- on- white ( fastpac 30- 2, size 3 stimulus) followed by blue- on- yellow ( fastpac 30- 2, size 5 stimulus) HVF analyzer, before and 1 hour after ingesting sildenafil 200 mg or placebo. Changes in mean deviation ( MD) were then compared between groups. For analysis, the MD of both eyes was averaged. No significant difference between the HVF of the OD and OS was found in any subject. TABLE 1. Effect of sildenafil on Humphrey visual fields Subject 1 2 3 4 5 6 7 8 Age ( yrs) 20 38 32 24 28 28 22 28 Sex F M F F F F F F Group Sildenafil Sildenafil Sildenafil Sildenafil Sildenafil Placebo Placebo Placebo Visual symptoms Yes Yes No No No No No No HVF MD ( dB) white- on- white baseline - 1.63 - 2.36 - 5.15 - 3.11 - 4.31 - 3.93 - 1.67 - 2.16 HVG MD ( dB) white- on- white repeat - 6.29 - 1.77 - 5.07 - 2.25 - 2.66 - 4.55 - 0.17 - 1.92 HVF MD ( dB) blue- on- yellow baseline 0.73 - 2.14 - 11.92 - 2.02 - 7.25 - 6.71 - 2.78 - 5.08 HVF MD ( dB) blue- on- yellow repeat - 17.10 0.16 - 11.64 - 2.50 - 4.38 - 10.74 - 3.17 - 4.58 HVF, Humphrey visual field; MD, mean deviation. 227 228 T. J. McCULLEY ET AL. . il ,8, A " " " " ,1. < t * , tt A » Fixation Losses: 0/ 0 Mean Deviation: - 4.89dB False Pos. Errors: False Neg. Errors: 0/ 10 0/ 9 Fixation Losses: Mean Deviation: 2/ 20 - 7.68dB False Pos. Errors False Neg. Errors: 0/ 12 4/ 13 Fixation Losses: Mean Deviation FIG. 1. Subject 1. Humphrey visual fields after sildenafil 200 mg: ( Top Left) white- on- white field, OS ; ( Top Right) white- on- white field, OD; ( Bottom Left) blue- on- yellow field, OS ; ( Bottom Right) blue- on- yellow field, OD. Fixation Losses: Mean Deviation False Pos. Errors: False Neg. Errors: RESULTS Table 1 summarizes the results. One sildenafil subject, a 20- year- old woman, developed bilateral superior field depression with a 17.8- dB decrease in MD on blue- on-yellow and bilateral infranasal depression with a 4.7- dB decrease in MD on white- on- white HVF ( Fig. 1). In addition to severe flushing and headache, which was experienced to a lesser degree by all sildenafil subjects, this subject reported abdominal discomfort. She was also one of two subjects who reported visual symptoms of a bluish haze and flashing lights. The remaining four sildenafil subjects performed similarly to the placebo group on blue- on- yellow ( mean change in MD ± standard deviation, 1.24 ± 1.60 dB and - 1.31 ± 2.40 dB, respectively, P = 0.15, t test) and white- on- white ( mean MD change, 0.8 ± 0.66 dB and 0.37 ± 1.07 dB, respectively, P = 0.54, t test) HVF perimetry. DISCUSSION After ingesting 200 mg sildenafil, most subjects had no detectable changes on blue- on- yellow or white- on-white HVF, including one sildenafil subject, who was tested while experiencing visual symptoms. This is consistent with previous published results ( 5). One of five sildenafil subjects performed poorly on HVF testing, with blue- on- yellow affected more than white- on- white. Severe nonvisual systemic side effects may have interfered with her test performance and may have been responsible for some of the observed changes; however, the reliability indices were good, which is not consistent with functional changes or an inability to concentrate. The relevance of this idiosyncratic response to sildenafil intake remains to be determined until more subjects have been tested. REFERENCES 1. Food and Drug Administration Joint Clinical Review. Animal pharmacology: mechanism of action, p 4. 2. Estrade M, Grondin P, Cluzel J, et al. Effect of a cGMP- specific phosphodiesterase inhibitor on retinal function. Eur J Pharmacol 1998; 352: 157- 63. 3. Food and Drug Administration Review and Evaluation of Pharmacol Toxicol Data. Section 1.2.3.6 Pharmacology: Activities related to mechanism of action: functional effects on other tissues expressing PDE5 enzyme: retinal effects 1998, pp 19- 21. 4. Food and Drug Administration Joint Clinical Review. Study 148- 223: An open, randomized, placebo controlled, four period crossover study to assess the effect of orally administered sildenafil ( 50, 100 and 200 mg) on visual function in healthy male volunteers, pp 160- 1. 5. Vobig MA, Klotz T, Staak M, et al. Retinal side- effects of sildenafil. Research Letters 1999; 353: 1- 2. / Neuro- Ophthalmol, Vol. 20, No. 4, 2000 |
