occasionally , however , it can be a sign of a more serious , often unrecognized condition .
we report on a patient with carboplatin - induced bilateral papilledema resulting in only partially reversible visual impairment . despite the fact that carboplatin is widely used in the treatment of a variety of common tumors ( including cancer of the lung , ovary , testis ) , this is the first report of carboplatin - induced papilledema following regular auc - determined dose .
reported cases of papilledema after carboplatin administration include two cases after high - dose carboplatin ( auc12 ) , one report using carboplatin and cisplatin simultaneously , and two patients to whom carboplatin was given in a fixed standard dose ( 400 mg / m )   rather than in a creatinine - clearance dependent dose ( auc ) .
a 70-year - old woman with stage iiic ( figo ) serous - papillary ovarian carcinoma started postoperative chemotherapy 5 weeks after optimal surgical debulking ( tah+bso ) in september 2005 .
concurrent medical conditions included stable coronary heart disease , controlled arterial hypertension and mild urinary retention as sole sequel of a previous injury to the lower back .
baseline renal function was normal with a calculated creatinine clearance of 100 ml / min ( cockroft formula ) .
chemotherapy consisted of a 3-weekly intravenous administration of carboplatin ( auc 5 mg / ml  min ) over 30 min and was well tolerated , grade 1 nausea , fatigue and grade 2 thrombocytopenia ( 53  10/l ) being the only adverse effects . on day 8 of the 4th cycle , however , the patient was admitted because of nausea , constipation and acute urinary retention . post - renal acute renal failure ( calculated creatinine clearance 40 ml / min ) was completely reversible after catheterization . at this time , she first complained about visual impairment in her right eye ( lack of focus and scattered blind spots ) .
the optic nerve head was at that time more prominent in the right eye than in the left eye , and there were some hemorrhages within the nerve fiber layer .
differential diagnosis of increased intracranial pressure due to meningeosis carcinomatosa or cerebral metastasis and anterior ischemic optic neuropathy ( aion ) due to anemia were discussed .
an mri of the brain showed no signs of intracranial pressure , leptomeningeal carcinomatosis or pathology of the optic nerve .
the serum tumor marker ca-125 had normalized ( from 1,541 u / ml pre- , and 114 u / ml postoperatively ) and complete remission was confirmed by abdominal ultrasound and chest x - ray .
however , after the 5th cycle the visual acuity decreased further , and new visual field losses in the left eye appeared . at the same time an increase of the bilateral papilledema was observed , particularly in the left eye . in contrast , the hemorrhages in the right eye had almost disappeared , and some signs of ischemia were now noted .
visual acuity had dropped to 20/100 in the left eye and there was a left relative afferent pupillary defect .
diagnostic lumbar puncture was performed and intracranial pressure was measured at 10 cm h2o . based on the normal intracranial pressure , the differential diagnosis of pseudotumor cerebri , a condition characterized by ophthalmopathy , papilledema and elevated intracranial pressure , was dismissed .
biochemical ( protein , glucose , ldh ) and cytological examination of the cerebral fluid was normal , without malignant cells .
tests for specific antibodies were not diagnostic : anti - cns and anti - yo antibodies titers were ( marginally ) elevated in the serum , but not in the cerebral fluid .
serum titers of anti - hu , anti - ri , anti - amphiphysin , anti - cv2 , anti - tr , anti - ma - antibodies and antibodies against retinal rods , cones , mueller cells as well as plexiform structures were all negative . in view of these results , an autoimmune syndrome - unusual in the context of ovarian cancer - seemed very unlikely .
based on the history , the clinical picture and the exclusion of other conditions via mri , cerebral fluid examination and serum antibody - titers , the diagnosis of bilateral carboplatin - induced papilledema was made .
chemotherapy was stopped after the 5th cycle and prednisolone was initiated at a dose of 100 mg / d for 2 weeks , then tapered over 10 weeks . while the visual acuity in the right eye was stable ,
( 2 years after cessation of chemotherapy ) , the optic nerve head showed some signs of optic atrophy with increased pallor and reduced visibility of the nerve fiber layer .
the optic nerve head was at that time more prominent in the right eye than in the left eye , and there were some hemorrhages within the nerve fiber layer .
differential diagnosis of increased intracranial pressure due to meningeosis carcinomatosa or cerebral metastasis and anterior ischemic optic neuropathy ( aion ) due to anemia were discussed .
an mri of the brain showed no signs of intracranial pressure , leptomeningeal carcinomatosis or pathology of the optic nerve .
the serum tumor marker ca-125 had normalized ( from 1,541 u / ml pre- , and 114 u / ml postoperatively ) and complete remission was confirmed by abdominal ultrasound and chest x - ray .
however , after the 5th cycle the visual acuity decreased further , and new visual field losses in the left eye appeared . at the same time an increase of the bilateral papilledema was observed , particularly in the left eye . in contrast , the hemorrhages in the right eye had almost disappeared , and some signs of ischemia were now noted .
visual acuity had dropped to 20/100 in the left eye and there was a left relative afferent pupillary defect .
diagnostic lumbar puncture was performed and intracranial pressure was measured at 10 cm h2o . based on the normal intracranial pressure , the differential diagnosis of pseudotumor cerebri , a condition characterized by ophthalmopathy , papilledema and elevated intracranial pressure , was dismissed .
biochemical ( protein , glucose , ldh ) and cytological examination of the cerebral fluid was normal , without malignant cells .
tests for specific antibodies were not diagnostic : anti - cns and anti - yo antibodies titers were ( marginally ) elevated in the serum , but not in the cerebral fluid .
serum titers of anti - hu , anti - ri , anti - amphiphysin , anti - cv2 , anti - tr , anti - ma - antibodies and antibodies against retinal rods , cones , mueller cells as well as plexiform structures were all negative . in view of these results , an autoimmune syndrome - unusual in the context of ovarian cancer - seemed very unlikely .
based on the history , the clinical picture and the exclusion of other conditions via mri , cerebral fluid examination and serum antibody - titers , the diagnosis of bilateral carboplatin - induced papilledema was made .
chemotherapy was stopped after the 5th cycle and prednisolone was initiated at a dose of 100 mg / d for 2 weeks , then tapered over 10 weeks . while the visual acuity in the right eye was stable ,
( 2 years after cessation of chemotherapy ) , the optic nerve head showed some signs of optic atrophy with increased pallor and reduced visibility of the nerve fiber layer .
in our case report , we postulate a direct toxic effect of carboplatin , as it was described in the 1970s for cisplatin . in the case of cisplatin cortical blindness ,
clinically , a loss of visual accuracy up to full blindness , often loss of color vision and scotomas were seen .
usually these symptoms are unilateral and initially mild , so that more chemotherapy is given before the diagnosis is made . a correlation with renal insufficiency and arterial hypertension
was reported [ 1 , 2 , 3 ] . the symptoms are usually reversible within weeks to months after cessation of the platinum treatment [ 2 , 3 ] , and the restoration of color vision can take up to 1 year .
it seems to be a cumulative toxicity , as all cases occurred after several cycles of chemotherapy .
furthermore , pharmacokinetic studies of cisplatin show a continual rise of the drug concentration in the cerebrospinal fluid with each cycle .
it is possible that the cerebrospinal fluid concentration is important for the occurrence of this toxicity : in one patient with blindness and a seizure equally high concentrations of cisplatin in the cerebrospinal fluid and the serum were measured .
the early recognition of this potentially severe side effect is paramount , since stopping chemotherapy before irreversible damage occurs is crucial .
it can occur at standard doses using creatinine - clearance dependent dose calculations ( auc ) and it can be partly irreversible .
since carboplatin is extensively used in a variety of common tumors in the palliative as well as the curative setting , this potentially severe side effect has to be kept in mind .
 we report on a patient with carboplatin - induced bilateral papilledema , as it was described in the 1970s for cisplatin . 
 loss of visual accuracy up to full blindness , often loss of color vision and scotomas can be seen as a result of cortical blindness , macula degeneration , retrobulbar neuritis and papilledema . 
 these symptoms are mostly unilateral and initially mild , so that more chemotherapy is given before the diagnosis is made 
 . the symptoms are usually reversible within weeks to months after cessation of the platinum treatment . 
 the therapeutic strategy is stopping the platinum treatment . in addition 
 the empiric use of corticosteroids is suggested . 
Introduction
Materials and Methods
Investigations and Differential Diagnosis
Diagnosis
Management and Follow-Up
Discussion
Conclusion