in june and july 2004 , a total of 1,620 cases of dengue fever and dengue hemorrhagic fever were reported in singapore ; 621 case - patients were admitted to our hospital . in the same period , retinal hemorrhages were diagnosed in 4 dengue fever patients in our hospital . as part of our protocol , we use polymerase chain reaction ( pcr ) ( while a patient is still febrile ) and serology ( after resolution of fever ) to confirm clinical diagnoses of dengue fever . real time - pcr is performed daily with commercial reagents ( artus gmbh , hamburg , germany ) on a light cycler ( roche diagnostics , penzberg , germany ) . serology is performed with the dengue duo igm and igg rapid strip test ( panbio , brisbane , queensland , australia ) . dengue serotypes were determined by immunofluorescence , with type - specific monoclonal antibodies , on virus cultured from serum taken early in the disease . four patients ( 3 women and l man ) had visual symptoms , which developed during hospitalization for dengue fever all denied any associated eye pain , photophobia , or increased tearing . except mild myopia in 1 patient , the average duration of fever before visual symptoms developed was 6.25 days ( range 58 ) . the onset of visual symptoms was usually observed within 1 day from the resolution of fever and the nadir of the thrombocytopenia . the average platelet count on the day of onset of symptoms was 36  10/l ( range 3344 ) . the lowest platelet count was recorded 1 day before the onset of symptoms in 1 patient , on the day of onset of symptoms in 2 patients , and 1 day after the onset of symptoms in 1 patient . the average platelet count at the nadir of thrombocytopenia was 33  10/l ( range 2640 ) . the clinical diagnosis of dengue fever was confirmed by pcr in 2 cases , by immunoglobulin ( ig)g and igm in 1 patient , and by igm in the remaining patient . all were serotype 1 . in 3 patients , visual symptoms resolved completely within 2 days , with full recovery of the patients ' visual acuities . improvement in visual symptoms was delayed and incomplete in patient 4 , and she had reduced visual acuity and metamorphopsia even after 2 months . singapore has experienced a steady rise in the incidence of dengue in recent years . in 2002 , a total of 3,937 cases of dengue were reported , followed by 4,785 cases in 2003 . as of september 11 , 2004 , a total of 4,985 cases were reported ( 2 ) . such complications typically occur toward the end of the febrile period , when the symptoms of classic dengue fever resolve . clinically , bleeding is usually mild and manifests itself as epistaxis , gum bleeding , hematuria , and menorrhagia . only occasional cases of severe gastrointestinal or retroperitoneal bleeding are reported . however , retinal hemorrhages are exceedingly rare as a complication of dengue fever . it showed only 4 case reports describing retinal hemorrhages associated with dengue fever ( 36 ) . ( 3 ) described a patient with dengue fever who had bilateral loss of vision . it increased to 20/100 in the right eye and 20/32 in the left eye 8 weeks after the patient was initially seen . wen et al . ( 4 ) described 24 patients with visual disturbances complicating dengue fever . the mean age of these patients was 32 ( range 1645 ) ; 19 of them had blurring of vision , while others complained of central scotoma , floaters , photophobia , or halo vision . visual symptoms developed in most patients 58 days ( range 215 ) after the onset of fever . seven of the remaining 9 patients were seen a long time after the onset of symptoms , and fundoscopic examination showed only mild , atypical maculopathy . optic nerve atrophy developed in 1 patient , and another patient was diagnosed with optic neuritis . our patients were also young , and visual symptoms developed 58 days after the onset of fever , consistent with current theories on the immunopathogenesis of dengue ( 7 ) . all our patients complained of decreased visual acuity , and fundoscopic examination showed macular hemorrhages and exudative maculopathy . careful review of clinical records allowed us to make additional observations , which have not been previously reported . in all our patients , visual symptoms developed shortly ( within 1 day ) before or after resolution of fever . although 3 patients improved symptomatically within 2 days , recovery was slower and incomplete in the fourth patient . although we see a considerable number of patients with dengue in our hospital , these patients are the first we have seen with dengue fever complicated by retinal hemorrhages . first , the recent , sharp rise in the incidence of dengue fever may have allowed us to observe this otherwise rare manifestation . or , their infection could have been caused by a particularly virulent type of dengue virus . we cultured virus from acute - phase serum samples from all 4 patients ; all were serotype 1 . in 2003 , 72% of 68 viruses isolated from sequential sera were serotype 2 , and 21% were serotype 1 . 70% of 37 sequential isolates belonged to serotype 1 and only 22% to serotype 2 ( barkham t. , unpub . data ) . although it is tempting to presume that the recent increase in incidence of retinal hemorrhages is associated with the unique virulence of serotype 1 virus , the fact that the dengue virus in all 4 patients belonged to serotype 1 may have been pure chance and merely reflect the fact that serotype 1 became predominant in 2004 . we are planning to clarify this issue by conducting a prospective study and would be pleased to hear from other centers with similar experiences . further studies will be necessary to determine the true incidence of retinal hemorrhage in patients with dengue fever . the onset of symptoms appears to coincide with the resolution of fever and the nadir of thrombocytopenia . although there is no specific therapy , retinal hemorrhage may be an indication for early and aggressive correction of thrombocytopenia .
we report 4 patients with retinal hemorrhages that developed during hospitalization for dengue fever . 
 onset of symptoms coincided with resolution of fever and the nadir of thrombocytopenia . 
 retinal hemorrhages may reflect the rising incidence of dengue in singapore or may be caused by changes in the predominant serotype of the dengue virus .