Spectrum of digoxin-induced ocular toxicity: a case report and literature review
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1 DOI /s CASE REPORT Open Access Spectrum of digoxin-induced oculr toxicity: cse report nd literture review Delphine Renrd 1*, Eve Rubli 2, Nthlie Voide 3, Frnçois Xvier Borrut 3 nd Lur E. Rothuizen 1 Abstrct Bckground: Digoxin intoxiction results in predominntly digestive, crdic nd neurologicl symptoms. This cse is outstnding in tht the intoxiction occurred in nongenrin nd induced severe, extensively documented visul symptoms s well s dysphgi nd proprioceptive illusions. Moreover, it went undignosed for whole month despite close medicl follow-up, illustrting the difficulty in recognizing drug-induced effects in polymorbid ptient. Cse presenttion: Digoxin 0.25 mg qd for tril fibrilltion ws prescribed to 91-yer-old womn with n estimted cretinine clernce of 18 ml/min. Over the following 2 3 weeks she developed nuse, vomiting nd dysphgi, snowy nd blurry vision, photopsi, dyschromtopsi, ggrvted pre-existing formed visul hllucintions nd proprioceptive illusions. She sw her fmily doctor twice nd visited the eye clinic once until, 1 month fter strting digoxin, she ws dmitted to the emergency room. Intoxiction ws confirmed by serum digoxin level of 5.7 ng/ml (reference rnge ng/ml). After stopping digoxin, generl symptoms resolved in few dys, but visul complints persisted. Exmintion by the ophthlmologist reveled decresed visul cuity in both eyes, 4/10 in the right eye (OD) nd 5/10 in the left eye (OS), decresed color vision s demonstrted by score of 1/13 in both eyes (OU) on Ishihr pseudoisochromtic pltes, OS ctrct, nd dry ge-relted mculr degenertion (ARMD). Computerized sttic perimetry showed non-specific diffuse ltertions suggestive of either bilterl retinopthy or optic neuropthy. Full-field electroretinogrphy (ERG) disclosed moderte diffuse rod nd cone dysfunction nd multifocl ERG reveled centrl loss of function OU. Visul symptoms progressively improved over the next 2 months, but multifocl ERG did not. The ptient ws finlly dischrged home fter 5 week hospitl sty. Conclusion: This cse is reminder of compliction of digoxin tretment to be considered by ny treting physicin. If digoxin is prescribed in vulnerble ptient, close monitoring is mndtory. In generl, when fcing new helth problem in polymorbid ptient, it is crucil to elicit complete history, with ll recent drug chnges nd detiled complints, nd to include drug dverse rection in the differentil dignosis. Keywords: Digoxin, Drug intoxiction, Vision impirment, Dyschromtopsi, Photopsi Bckground Digitlis glycosides long history in medicl prctice hs been beutifully explored by English phrmcologist Jeff K. Aronson some 20 yers go. His in-depth study, centered on the work by 18th century English physicin nd scientist Willim Withering, shows tht their nrrow therpeutic mrgin hs been recognized nd delt with for severl thousnd yers [1]. *Correspondence: delphine.renrd@chuv.ch 1 Division of Clinicl Phrmcology, University Hospitl of Lusnne, Bugnon 17 01, 1011 Lusnne, Switzerlnd Full list of uthor informtion is vilble t the end of the rticle Digoxin is the min form of digitlis mediclly used in Switzerlnd tody. It is extrcted from the leves of the plnt Digitlis lnt. It combines with nd reversibly inhibits the cell membrne N+/K+-ATPse, inducing n increse in intrcellulr clcium, intrcellulr sodium, nd extrcellulr potssium. In the hert, this leds to n increse in myocrdium s strength of contrction nd excitbility, s well s to decrese in conduction nd depolriztion velocity in the trio-ventriculr node. Current indictions to digoxin re restricted to second line tretment for proxystic or permnent tril fibrilltion (AF), second line tretment for symptomtic hert filure with rpid AF, or s lst resort for severe, 2015 Renrd et l. This rticle is distributed under the terms of the Cretive Commons Attribution 4.0 Interntionl License ( which permits unrestricted use, distribution, nd reproduction in ny medium, provided you give pproprite credit to the originl uthor(s) nd the source, provide link to the Cretive Commons license, nd indicte if chnges were mde. The Cretive Commons Public Domin Dediction wiver ( publicdomin/zero/1.0/) pplies to the dt mde vilble in this rticle, unless otherwise stted.
2 Pge 2 of 8 symptomtic systolic hert filure (left ventriculr ejection frction 40 %) [2, 3]. Phrmcologicl properties of digoxin re s follows: biovilbility %, distribution volume 5 7 l/kg, poor protein binding (25 %), time to pek concentrtion 1 h, time to pek effect 6 h fter orl dministrtion. Metbolism is negligible nd elimintion essentilly occurs through glomerulr filtrtion, with smll contribution of tubulr secretion involving P-glycoprotein. Digoxin hs long hlf-life (40 h; 100 h nd beyond in kidney disese). Usul mintennce dosing is 0.25 mg qd. In kidney disese, empiricl dose reductions re proposed ccordingly, for exmple % of usul dosing for cretinine clernce (CrCl) of ml/min ccording to the Cockroft-Gult formul, % of usul dosing for CrCl of ml/min, nd % of usul dosing for CrCl <20 ml/min. These re generl guidelines only, s plsm cretinine is poor indictor of kidney function in very ill or srcopenic elderly people. Drug monitoring nd scrupulous follow-up re mndtory in such cses. Digoxin toxicity predominntly mnifests s digestive or neurologicl symptoms. Crdic symptoms re less frequent but re relted to the seriousness of digoxin poisoning, the overll rte of mortlity being estimted t 25 %. Out of rnge potssium, clcium or mgnesium levels cn modulte digoxin ction. Neurologic symptoms re multifold, including hedche, confusion, somnolence, ftigue, restlessness nd visul symptoms. Elderly ptients re more susceptible to digoxin toxicity for vriety of resons including kidney disese, decrese in musculr mss, frequent polyphrmcy (diuretics nd miodrone being the most frequent t-risk co-mediction), nd poor dherence due to sensory nd cognitive impirment [4]. The erliest report of digitlis-ssocited oculr toxicity we could esily ccess ws published in 1925 in the Boston Medicl nd Surgery Journl, ncestor of the New Englnd Journl of Medicine [5]. According to the uthors: Sensory disturbnces ssocited with n overdose of digitlis [ ] re met with rrely, nd even then my esily be overlooked simply becuse their mening is not cler. They proceed with reporting the illness of 55-yer-old womn who, fter 1 yer of regulrly tking digitlis, developed n ttck of filing vision. Everything ppered yellow before her eyes. Lter on, She ws unble clerly to distinguish objects nd persons t distnce, nd everything seemed to be bthed in very intense glring white light [ ]. The ir seemed filled with yellow snow, nd the grss ppered distinctly blue in color. The sky ppered green. At times she hd double vision, [ ] t times she sw T shped objects in the sky or ny blnk surfce. The uthors conclude: It my be tht the condition of yellow vision is more common thn we suppose nd tht more creful questioning of ptients with toxic mnifesttions of digitlis will revel this fct. As geritricins, ophthlmologists, nd clinicl phrmcologists, we recently cred for n elderly womn suffering from severl visul symptoms relted to digoxin intoxiction. We tell her story s well documented cse of digoxin oculr toxicity, s well s reminder tht the need for creful questioning still holds true in medicl prctice tody. Cse presenttion A 91-yer-old femle ptient, weight 56 kg, height 151 cm, ws dmitted to the emergency room (ER) of tertiry hospitl complining bout dysphgi, vomiting nd blurry vision. She ws in ltered generl condition but hemodynmiclly stble; detiled physicl exmintion ws unremrkble. Electrocrdiogrphy showed pced rhythm, 60/min. She felt so ill she repetedly sid she d hve to enter nursing home. The ptient lived lone t home. She got dily help from her dughter nd the locl home cre services, nd sometimes mde mistkes while mnging her mediction. She suffered from multiple co morbidities, including hypertension, hypercholesterolemi, type 2 dibetes, ischemic hert disese with hert filure, chronic kidney disese (cretinine clernce ccording to Cockroft-Gult formul, CrCl, 18 ml/min), gout, nd indolent brest cncer. A pcemker hd been implnted 2 yers erlier for permnent tril fibrilltion (AF) with insufficiently controlled ventriculr rte. She hd benefited from right eye ctrct surgery. She ws under the regulr cre of generl prctitioner (GP), nephrologist, crdiologist, n ophthlmologist nd n oncologist. Her mediction consisted of cenocoumrol qd (dosing ccording to Interntionl Normlized Rtio, trgeted rnge ), metoprolol 100 mg qd, lisinopril 5 mg qd, torsemide 20 mg qd, simvsttin 20 mg qd, nstrozole 1 mg qd, ibndronte 150 mg monthly, lorzepm 0.5 mg qd, folte 5 mg qd, clcium 500 mg/choleclciferol 400 IU bd, nd zolpidem 5 mg qd s needed. Digoxin, 0.25 mg qd, nd diltizem, 90 mg qd, hd been strted exctly 1 month erlier by her crdiologist for AF with rpid ventriculr response. In letter to the GP sent 7 dys fter the ptient ws strted on digoxin, the crdiologist mentioned the need for mesuring the digoxin level nd dpting the dosing, without specifying dedline. He lso reported intending trioventriculr node bltion therpy 5 weeks lter. A detiled history given by the ptient, her dughter, nd the home cre services reveled tht on the 7th dy fter strting digoxin, the ptient suffered fll, which led her GP to stop diltizem on the 8th dy. On the 13th
3 Pge 3 of 8 dy, she hd digestive symptoms nd difficulty eting. From the 18th dy on, she complined of significnt loss of vision in both eyes, seeing everything in white. Five months previously, she hd been routinely exmined by her ophthlmologist. Visul cuity ws 10/10 difficult in both eyes, nd fundus exmintion disclosed the presence of slight retinl pigment epithelium chnges comptible with erly dry ge-relted mculr degenertion (ARMD). On the 21th dy of digoxin therpy, n emergency consulttion t the eye clinic reveled decresed visul cuity in both eyes (4/10 OD nd 5/10 OS), mture ctrct in the left eye nd dry ARMD in both eyes. From then on, the ptient lost 5 kg becuse of nuse nd vomiting, nd her vision remined severely impired. Her symptoms vried from dy to dy but included blurry vision (she couldn t red printed text nymore), snowy vision (everything ppered to be bthed in white light), tendency to collide with objects on her right side, dyschromtopsi (she ws seeing blue or purple spots when she closed her eyes, vivid colors ppered to be fded), formed visul hllucintions of little humn figures tht did not frighten her ppering either upon wkening (hypnopompic) or shortly before flling sleep (hypngogic), nd feeling s if she ws on fishing bot when lying in bed (proprioceptive illusions). Digoxin intoxiction ws suspected on dmission 1 month fter its initition, nd confirmed when the serum level ws mesured to be 5.7 ng/ml [ ]. 1 Other relevnt lbortory results were s follows (reference rnge in brckets): cretinine 183 µmol/l [44 80], sodium 144 mmol/l [ ], potssium 4.0 mmol/l [ ], clcium 2.41 mmol/l [ ]. Digoxin ws definitively stopped, nd further levels were s follows (ll smples were tken t 6 m, dy 0 = dy of ER dmission): Dy 3: 4.0 ng/ml. Dy 10: 1.1 ng/ml. Dy 18: not to be detected. On this bsis, we estimted the hlf-life to be pproximtely h in this ptient t tht time. Chest rdiogrphy, brin computed tomogrphy scn nd oesogstric studies provided no contributive finding in explining the symptoms. After digoxin withdrwl, nuse nd vomiting were first to dispper in the next few dys. Her generl condition then improved, the ptient gined weight nd benefited from hospitl rehbilittion progrm. On the 17th dy fter ER dmission, detiled ophthlmologicl exmintion ws performed. Visul symptoms were persistent, including snowy nd blurry vision, 1 The lst time the ptient hd tken digoxin could not be determined with certinty, but ws supposed to hve been pproximtely 48 h prior to blood smpling. peripherl fixed photopsis nd dyschromtopsi, ll comptible with digoxin intoxiction, s well s formed visul hllucintions occurring systemticlly when the ptient fell sleep (hypngogic visul hllucintions). Visul cuity ws decresed in both eyes (4/10 OD with S 1.25, C 1.5 t 103 nd 5/10 OS with S+1.25) nd color vision testing with Ishihr pseudoisochromtic pltes disclosed severe red-green dyschromtopsi (only 1/13 pltes correctly identified with either eye). Slit-lmp exmintion showed pseudophkic OD nd mture corticonucler OS ctrct. Introculr pressures were norml (12 mmhg OU). Funduscopy reveled norml optic nerve hed with perippillry trophy OU, norml retinl vessels nd bilterl miniml mculr chnges comptible with bilterl erly dry ARMD. Computerised sttic perimetry (Octopus model 300) showed non-specific diffuse sensitivity loss consistent with bilterl diffuse retinopthy. Compred to our normtive dt for the ge group, full-field photopic nd scotopic ERGs confirmed moderte diffuse dysfunction more pronounced for cones thn rods (photopic nd scotopic b-wve mplitude ws decresed to 60 % of the lower norml vlues for the ge). Qulittive interprettion of multifocl ERG disclosed diffuse decrese of mplitude mostly in the centrl ten degrees. The ptient ws finlly dischrged home 44 dys fter ER dmission. She ws still living t home 6 months fter ER dmission ccording to elicited follow-up. At tht time, tests showed subtle improvement of visul cuity (6/10 OD nd 5/10 OS), persistent severe red-green dyschromtopsi (1/13 on Ishihr test OU), nd slight non significnt mplitude increse on the multifocl ERG. Unfortuntely, she denied further ophthlmologic exmintions beyond follow-up t 6 months. Discussion nd literture review In this ptient, the time course nd chrcteristics of the clinicl evolution, nd the constelltion of symptoms were ttributed with high probbility to digoxin intoxiction, notbly in view of the elevted drug level (score of 9/13 ccording to the Nrnjo Adverse Drug Rection Probbility Scle [6]). Mny risk fctors for these dverse drug rections were present: 1. A drug with nrrow therpeutic mrgin ws dministered t stndrd dosing with insufficient pre-defined follow-up strtegy to prticulrly vulnerble ptient becuse of dvnced ge, polymorbidity, polymediction with questionble dherence, nd pre-existing dvnced kidney disese s well s functionl nd oculr impirment. Specific intercting drugs were diltizem (which increses exposure
4 Pge 4 of 8 to digoxin through uncertin mechnisms, possibly by inhibiting P-glycoprotein) nd torsemide nd lisinopril (which ggrvte renl filure nd the risk of dehydrtion nd electrolyte imblnce). 2. Mny people were involved in the cre of the ptient, nd her symptoms were, t lest in the beginning, entirely non-specific. Loose communiction between the crdiologist nd the GP, dilution of responsibilities nd filure to rpidly identify nd incriminte drugs s plusible cuse were ll elements tht could contribute to the dely in dignosing this potentilly life-thretening intoxiction. Further discussion will focus on neurologic symptoms, with prticulr emphsis on visul symptoms. Although dysphgi ws mentioned on dmission, it is difficult to be positive it ws relly prt of the clinicl picture, becuse the ptient then stopped complining bout it nd lter even denied hving ever suffered from it. Two cse reports describe dysphgi in digoxin intoxiction in elderly women, but the clinicl picture ws more clercut [7, 8]. Proprioceptive illusions re described in nother cse report s [the ptient complined tht] the room ws hilly nd tht the bed ws continuously sliding downhill [9]. Disturbnces of vision during digoxin tretment re less common thn crdic or other non crdic symptoms, but re considered by some uthors to be more specific. In this ptient, crdic symptoms re likely to hve been conceled by the implnted pcemker. The spectrum of visul complints include decresed visul cuity, centrl scotoms or visul field reduction, glre, photopsi most pronounced in dylight, photophobi, blurry or snowy vision, visul hllucintions, diplopi, nd dyschromtopsi including xnthopsi (yellow vision), cynopsi (blue vision) nd chloropsi (green vision). Dyschromtopsi cn be symptomtic nd reveled only by forml testing; severl studies report positive correltion between the totl error score t testing nd serum digoxin level. A more recent study in 30 elderly hospitlized ptients receiving digoxin mintennce therpy compred to controls did not confirm this correltion, but the uthors reported high incidence of impired color vision t serum digoxin levels considered therpeutic s well s supr-therpeutic, speking for limited vlue of forml color vision testing for the detection of toxicity in the ged [10]. The mechnism underlying oculr symptoms is presumed to be relted to N+ K+ATPse inhibition but remins specultive [9, 11]. Ophthlmologic tests considered most useful to support dignosis of digoxin intoxiction re photopic nd scotopic ERG seeking for b-wve delyed implicit time nd decresed b-wve mplitude. In our ptient, visul symptoms improved fter stopping digoxin, yet some persisted for severl weeks, long fter drug levels becme undetectble, nd others hd not resolved fter 6 months. We offer severl possible explntions for this. First, digoxin elimintion ws slow becuse of its high volume of distribution nd prolonged hlf-life in this ptient. It could lso be hypothesized tht serum digoxin levels more poorly correlte with certin specific phrmcodynmic effects (for exmple, durtion of the effect my possibly vry ccording to different clernces from deep tissue comprtments or vribility in inhibition by digoxin of different N /K+-ATPse isoforms in different body tissues). Second, the ptient my hve been more worried bout nd inclined to express oculr symptoms becuse of the ttention given to them by clinicins. Third, the underlying eye diseses my themselves hve evolved over the time. Eventully, the ptient refused to continue ophthlmologic follow-up beyond 6 months hereby escping longer monitoring. Arbitrrily strting our literture review in the seventies, we found totl of 15 references to cse reports of impired vision during digoxin mintennce therpy or in situtions of chronic suprtherpeutic digoxin levels. These publictions describe totl of 52 ptients (Tble 1), with only five cses described in more recent yers (since 2000). Qulity of documenttion nd degree of detil re highly unequl mong studies, which does not llow for quntittive nlysis. As whole, most ptients re ged (>65-yer-old), with only one ptient being under 40. Oculr symptoms re numerous. Digoxin levels lso vry gretly, but mny re in the suprtherpeutic or more clerly toxic rnge. Finlly, full resolution is lmost lwys witnessed over the course of 1 2 weeks, but here gin follow-up is heterogeneous nd often of short durtion. Conclusion We describe cse of digoxin intoxiction in ptient t highest risk for this dverse outcome due to different endogenous nd exogenous fctors: dvnced ge, polymorbidity including severe chronic kidney disese, preexistent oculr disese, insufficient communiction mong crers nd filure to include drug-induced dverse rection in the differentil dignosis. It is unique by its extensive description of ophthlmologic findings, over 6 month follow-up. Above ll, this cse is reminder of compliction of digoxin tretment to be considered by ny treting physicin. If digoxin is prescribed in vulnerble ptient, close monitoring is mndtory. In generl, when fcing new helth problem
5 Pge 5 of 8 Tble 1 Synopsis of cses of visul symptoms in digoxin mintennce therpy or digoxin chronic intoxiction published in Pubmed, References Ptient(s) (F = femle or M = mle, ge in yers) Digoxin tretment (mg qd unless otherwise specified) Tretment durtion Oculr symptoms Precipitting fctors Digoxin level (ng/ ml) Specific ophthlmologic exmintion Evolution fter stopping digoxin (or, in few cses, significntly decresing the dose) Mnninen [12] Volpe nd Sove [13] Aronson nd Ford [11] Weleber nd Shults [14] n = 5 2 M, 3 F, n = 3 2 M, 1 F, n = 10 (experiment on subjects previously published) Severl yers Yellow hue to objects, formed visul hllucintions (nimls, people, household objects) Not specified in this rticle M, four times dily Not specified in this rticle At lest severl months Indistinct vision of objects None detected 1.3 (n = 1) (n = 4) ) b) Dose increse to mg bd c) Not specified in this rticle Glre sensitivity, dimming of vision, silver flshes in the form of rectngles in the right visul field, hlos round lights, no yellow vision Closson [9] F, months Blue, green nd yellow veils floting everywhere, plesnt visions of trees, sun, etc. No color vision impirment. Chumn nd LeSge [15] n = 2 ) M, 79 b) M, 61 ) 0.25 nd on lternte dys b) ) Objects ppering more white thn usul b) Objects were seen s if they were in fog nd colors ppered to be fded Concomitnt quinidine sulfte dministrtion Concomitnt hydrochlorothizide nd trimterene prescription for 2 dys ) 5.0 b) 6.5 c) 2.7 Not specified in this rticle Ishihr pltes: some degree of difficulty in seeing t the pltes for green red vision b 2 weeks Not mentioned b fter drug level corrected Frnsworth-Munsell 100-Hue test (upper limit of norml for colour defect score = 140). The medin colour defect score in toxic ptients (212) ws significntly higher thn tht of controls (85), flling to the significntly lower vlue of 127 fter withdrwl of digoxin [ ] 3.5 Frnsworth-Munsell 100-Hue error scores: 569 OD, 646 OS Electrooculogrm: high initil light-to-drk rtios (3.50 OD, 3.20 OS) Electroretinogrm: No detectble drk-dpted cone-medited response (x wve). Light-dpted cone-medited response (b wve) significntly subnorml nd significntly prolonged in implicit time. Drk-dpted rod-medited b wve significntly subnorml nd prolonged in implicit time. Amplitude of the scotopic wve (cornel negtive pek) nd bx wve (cornel positive pek) t mximl stimulus intensity subnorml. 2.2 ) 13.1 b) 6 Frnsworth-Munsell 100-Hue test error score: ) 497 b) 854 Ishihr pltes: ) 7 errors/filed b) 14 errors/filed AOH-R-R plte defects: ) medium for green red nd blue-yellow b) strong for red-green nd blue-yellow fter 2 weeks
6 Pge 6 of 8 Tble 1 continued References Ptient(s) (F = femle or M = mle, ge in yers) Digoxin tretment (mg qd unless otherwise specified) Tretment durtion Oculr symptoms Precipitting fctors Digoxin level (ng/ ml) Specific ophthlmologic exmintion Evolution fter stopping digoxin (or, in few cses, significntly decresing the dose) Merté et l. [16] Hobley nd Lwrenson [17] Piltz et l. [18] Butler et l. [19] n = 14, medin ge 72 yers (prospective study compring subjects with digoxin nd digitoxin intoxiction) At lest 6 weeks One-third of ptients complined bout blurry vision, photopsi nd impirment of color vision F, months Scintillting visul field loss, in ttcks ech lsting bout 20 min. No ltertion in color vision n = 3 ) F, 88 b) F, 78 c) F, 58 (with retinitis pigmentos nd high myopi) n = 6 ) F, 76 b) F, 79 c) F, 82 d) M, 75 e) F, 85 f ) M, 66 ) 0.25 b) 0.25 c) 0.25 ) 0.25 b) c) 0.25 d) e) 0.25 f ) 0.25 ) b) 2 months c) ) Progressive, generlized dimming of vision OU b) decresed visul cuity bilterlly with snowy vision, obscuring vision of colors c) extreme drkness of vision ) Light through verticl blinds b) Flshing lights temporlly c) Yellow nd white sprks dncing nd swirling over whole visul field d) Flickering in periphery of vision e) Glre, brightness OD f ) White glre, snow on grss, trees, decresed visul cuity nd color discrimintion Medin digoxin level 2.98 ( ) Frnsworth-Munsell 100-Hue test: medin number of errors 170 <2 Friedmn Visul Field Anlyser Mrk II: reltive defect of visul field between 15 nd 20 degrees in temporl field OD, nd between 15 nd 20 nsl field OS Frnsworth-Munsell 100-Hue error score: 20 OD, 84 OS Ishihr pltes: results norml OU ) 6.1 b) 2.2 c) 4.5 ) b) c) 0.8 d) e) 0.7 f ) 0.2 Electroretinogrm (ERG) ) mplitude of drk dpted flsh ERG decresed to ~ 20 % of norml OD, nd 45 % of norml OS Goldmn perimetry b) generlized depression of the field nd 10-degree reltive centrl scotom to the I3E isopter OS Ishihr pltes b) correctly identified only the test plte (not ll tests vilble for ll ptients; no specific tests mentioned for ptient c) Electroretinogrm cone b-wve explicit time [ms]: ) 30.0 OD, 28.8 OS b) 40 OD c) not done d) 37.6 b e) 35.4 b f ) 36.4 OD, 36.0 OS Significnt improvement, follow-up restricted to 8 dys ) Prtil resolution only t 3 months b) t 1 month c)
7 Pge 7 of 8 Tble 1 continued References Ptient(s) (F = femle or M = mle, ge in yers) Digoxin tretment (mg qd unless otherwise specified) Tretment durtion Oculr symptoms Precipitting fctors Digoxin level (ng/ ml) Specific ophthlmologic exmintion Evolution fter stopping digoxin (or, in few cses, significntly decresing the dose) Wolin [20] n = 2 ) F, 68 b) F, 63 ) Shimmering lights b) Blurred vision OU ) 1.7 b) 1.0 Humphrey utomted visul field testing nd fluorescein ngiogrphy: ) not mentioned b) generlized depression OU with greter inferior thn superior visul field loss b Honrubi et l. [21] Ngi et l. [22] ) in 2 weeks b) Prtil resolution Gödecke- Koch et l. [23] Oishi et l. [24] M, 72 n = 2 ) M, 72 b) M, 54 F, 90 (severe eye disese fter bilterl zoster infection) 2 months Photopsi in the whole visul field 0.2 Severe decrese in visul cuity Visul hllucintions (people, yellow hy, colored surfces) F, yer Sudden onset of binoculr photopsi in the periphery of visul fields 2.75 Humphrey utomted visul field testing: norml (81 points) Frnsworth-Munsell 100-Hue test: norml Electroretinogrm (ERG): 30 Herz-flicker ERG nd photopic ERG: decresed mplitude b 1.9 Dirrhe with dehydrtion nd hyperkliemi 1.7 Significnt improvement fter 3 dys in 2 weeks OD right eye, OS left eye, OU both eyes No informtion vilble b No further detils or quntifiction vilble
8 Pge 8 of 8 in polymorbid ptient, it is crucil to elicit complete history, with ll recent drug chnges nd detiled complints, nd to include drug dverse rection in the differentil dignosis. Consent Written informed consent ws obtined from the ptient for publiction of this cse report. A copy of the written consent is vilble for review by the Editor-in-Chief of this journl. Authors contributions DR hndled the report to clinicins, the notifiction to phrmcovigilnce uthorities, nd wrote the pper. ER cred for the ptient, reported the dverse effect, nd revised the pper. NV nd FXB cred for the ptient, wrote the prts of the cse report pertining to specific ophthlmology topics, nd revised the pper. LER supervised the drug-induced dverse effect registrtion nd revised the pper. All uthors red nd pproved the finl mnuscript. Author detils 1 Division of Clinicl Phrmcology, University Hospitl of Lusnne, Bugnon 17 01, 1011 Lusnne, Switzerlnd. 2 Service de géritrie et rédpttion géritrique, CHUV, CUTR Sylvn, Ch. de Sylvn 10, 1066 Eplinges, Switzerlnd. 3 Déprtement d ophtlmologie, Université de Lusnne, Fondtion Asile des Aveugles, Hôpitl ophtlmique Jules-Gonin, v. de Frnce 15, 1000 Lusnne 7, Switzerlnd. Acknowledgements None. This pper is cse report describing events hving occurred in the nturl course of disese (dverse drug event) nd stte-of-the rt medicl cre during the ensuing hospitl sty. No reserch-oriented intervention ws delivered to the ptient. The ethics committee [Commission cntonle (VD) d éthique de l recherche sur l être humin, Lusnne, Switzerlnd] gve us written pprovl for this publiction. Complince with ethicl guidelines Competing interests The uthors declre tht they hve no competing interests. Received: 22 August 2014 Accepted: 18 August 2015 References 1. Aronson JK. An ccount of foxglove nd its medicl uses Oxford: Oxford University press; McMurry JJ, Admopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Flk V, Filipptos G, Fonsec C, Gomez-Snchez MA, et l. ESC Guidelines for the dignosis nd tretment of cute nd chronic hert filure 2012: the tsk force for the dignosis nd tretment of cute nd chronic hert filure 2012 of the Europen Society of Crdiology. Developed in collbortion with the Hert Filure Assocition (HFA) of the ESC. Eur Hert J. 2012;33(14): Cmm AJ, Lip GY, De Cterin R, Sveliev I, Atr D, Hohnloser SH, Hindricks G, Kirchhof P. Guidelines-CPG ESCCfP, document R: 2012 focused updte of the ESC guidelines for the mngement of tril fibrilltion: n updte of the 2010 ESC guidelines for the mngement of tril fibrilltion developed with the specil contribution of the Europen Hert Rhythm Assocition. Europce Eur Pcing Arrhythm Crd Electrophysiol J Work Groups Crd Pcing Arrhythm Crd Cell Electrophysiol Eur Soc Crdiol. 2012;14(10): Puts E, Lopez C, Gouronnec A, Grveline S, Peyron I, Lpostolle F. Focus on digitlis intoxiction in the elderly. Report of cse treted with digoxin-specific Fb ntibody frgments. Geritrie et psychologie neuropsychitrie du vieillissement. 2012;10(4): Jckson HJ, Zerfs LG. A cse of yellow vision ssocited with digitlis poisoning. Boston Med Surg J. 1925;192: Nrnjo CA, Busto U, Sellers EM, Sndor P, Ruiz I, Roberts EA, Jnecek E, Domecq C, Greenbltt DJ. A method for estimting the probbility of dverse drug rections. Clin Phrmcol Ther. 1981;30(2): Kelton JG, Scullin DC. Digitlis toxicity mnifested by dysphgi. JAMA J Am Med Assoc. 1978;239(7): Cordeiro MF, Arnold KG. Digoxin toxicity presenting s dysphgi nd dysphoni. BMJ. 1991;302(6783): Closson RG. Visul hllucintions s the erliest symptom of digoxin intoxiction. Arch Neurol. 1983;40(6): Lwrenson JG, Kelly C, Lwrenson AL, Birch J. Acquired colour vision deficiency in ptients receiving digoxin mintennce therpy. Br J Ophthlmol. 2002;86(11): Aronson JK, Ford AR. The use of colour vision mesurement in the dignosis of digoxin toxicity. Q J Med. 1980;49(195): Mnninen V. Letter: impired colour vision in dignosis of digitlis intoxiction. Br Med J. 1974;4(5945): Volpe BT, Sove R. Formed visul hllucintions s digitlis toxicity. Ann Intern Med. 1979;91(6): Weleber RG, Shults WT. Digoxin retinl toxicity. Clinicl nd electrophysiologicl evlution of cone dysfunction syndrome. Arch Ophthlmol. 1981;99(9): Chumn MA, LeSge J. Color vision deficiencies in two cses of digoxin toxicity. Am J Ophthlmol. 1985;100(5): Merté H-J, Hollwich F, Numnn GOH, Gloor B. Frbsinnstörungen bei subtoxischen und toxischen Digoxin-und Digitoxinsereumkonzentrtionen. Klin Mbl Augenheilk. 1988;193: Hobley A, Lwrenson J. Oculr dverse effects to the therpeutic dministrtion of digoxin. Ophthlmic Physiol Opt J Br Coll Ophthlmic Opt. 1991;11(4): Piltz JR, Wertenbker C, Lnce SE, Slmovits T, Leeper HF. Digoxin toxicity. Recognizing the vried visul presenttions. J Clin Neuro-Ophthlmol. 1993;13(4): Butler VP Jr, Odel JG, Rth E, Wolin MJ, Behrens MM, Mrtin TJ, Krdon RH, Gours P. Digitlis-induced visul disturbnces with therpeutic serum digitlis concentrtions. Ann Intern Med. 1995;123(9): Wolin MJ. Digoxin visul toxicity with therpeutic blood levels of digoxin. Am J Ophthlmol. 1998;125(3): Honrubi A, Andres JM, Alcine F, Bons E, Fernndez J, Lujn B. Visul disorders induced by therpeutic levels of digoxin. Archivos de l Sociedd Espnol de Oftlmologi. 2000;75(1): Ngi N, Ohde H, Betsuin Y, Mtsukur S, Kigsw K, Mshim Y, Oguchi Y. Two cses of digitlis toxicity with reversible nd severe decrese of visul cuity. Nippon Gnk Gkki zsshi. 2001;105(1): Godecke-Koch T, Schlimme J, Rd D, Emrich HM. Chrles Bonnet syndrome in n elderly ptient with bilterl vision loss, hyperthyroidism nd reltive digitlis overdose. Der Nervenrzt. 2002;73(5): Oishi A, Miymoto K, Kshii S, Yoshimur N. Photopsi s mnifesttion of digitlis toxicity. Cn J Ophthlmol. 2006;41(5): Submit your next mnuscript to BioMed Centrl nd tke full dvntge of: Convenient online submission Thorough peer review No spce constrints or color figure chrges Immedite publiction on cceptnce Inclusion in PubMed, CAS, Scopus nd Google Scholr Reserch which is freely vilble for redistribution Submit your mnuscript t
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