HEMORRHAGIC UNILATERAL

RETINOPATHY
VERONICA A. KON GRAVERSEN, MD,* LEE M. JAMPOL, MD, TRAVIS MEREDITH, MD,*
MAURICE LANDERS, III, MD,* JASON SLAKTER, MD, ALEXANDER J. BRUCKER, MD,
MAURICE RABB, MD
Purpose: To evaluate the possible etiologies of a hemorrhagic unilateral retinopathy in
healthy patients.
Methods: Retrospective case series and review of the literature. All patients underwent
a detailed ophthalmologic evaluation and analyses of their medical histories.
Results: Eleven eyes of 10 patients with unexplained unilateral, predominantly deep,
intraretinal hemorrhages were identied. All patients were women. Mean age of the
subjects was 48.4 years (range, 2583 years). The main complaint at presentation was
sudden visual loss, with visual acuity ranging from 20/20 to hand motion. The mean
follow-up was 17 months, and the 9 eyes with follow-up showed spontaneous resolution
of the hemorrhages and marked improvement of vision. There was no history of Valsalva
maneuver or strenuous exercise. The patients were healthy at presentation and during
follow-ups as long as 84 months.
Conclusion: This series depicts the characteristics of a possible new entity with a review
of the differential diagnosis. The visual outcome was excellent.
RETINA 34:483489, 2014

adult syndrome.15,16 In some cases, no etiology could

be identied.
The constellation of ndings in the 11 eyes of our
patients revealed spontaneous, predominantly deep,
unilateral intraretinal hemorrhages. These deep hemorrhages were larger in size than previously reported
spontaneous hemorrhages. No systemic or ocular
conditions were identied. The clinical course was
a resolution of the hemorrhages and near-complete
recovery of vision in eight patients (nine eyes) with
available follow-up. This report describes the clinical
and imaging features and outcomes of this entity with
discussion of the differential diagnosis.

ntraretinal hemorrhages may develop as a result of

a large number of ocular and systemic conditions,
including anemia, coagulopathies, hyperviscosity, leukemias, vascular occlusive disease, hypertension, diabetes, and ocular neovascularization.1 Small unilateral
hemorrhages in the posterior pole have been previously reported in young adults.26 The occurrence of
retinal hemorrhages in otherwise healthy people has
also been documented after blunt trauma, Valsalva
maneuver,7,8 extreme physical exertion, sexual activity,9 exposure to high altitudes,1012 stress because of
the elevation of vascular hydrostatic pressure at eye
level,13 patients with genetic predisposition,14 and shaken
From the *Department of Ophthalmology, University of North
Carolina at Chapel Hill, Chapel Hill, North Carolina; Deceased;
Department of Ophthalmology, Feinberg School of Medicine,
Northwestern University, Chicago, Illinois; Vitreous-Retina-Macula
Consultants of New York, New York, New York; and Department
of Ophthalmology, Scheie Eye Institute, Philadelphia, Pennsylvania.
None of the authors have any nancial/conicting interests to
disclose.
Supported in part by unrestricted grants from Research to Prevent
Blindness, Inc, New York, NY (Northwestern University/University
of North Carolina at Chapel Hill).
Reprint requests: Veronica A. Kon Graversen, MD, Department
of Ophthalmology, University of North Carolina at Chapel Hill,
9303 Fawn Lake Dr, Raleigh, NC 27617; e-mail: vkongrav@
unch.unc.edu

Patients and Methods

In 1996, during a Retina meeting, Maurice Rabb,
MD, presented a young healthy patient with an
unusual pattern of deep intraretinal hemorrhages and
no ocular or systemic diseases. Subsequent to the
presentation, several retinal specialists brought forward similar cases. Dr. Rabb categorized these cases.
Recently, we encountered an identical patient and have
retrospectively analyzed these cases and reviewed the
literature. We collected 11 eyes of 10 patients with
483

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RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2014  VOLUME 34  NUMBER 3

a mean age of 48.4 years (range, 2583 years). Demographic information, preexisting conditions, medications, and details of the initial and nal examinations,
including visual acuity, intraocular pressure, angiography, and optical coherence tomography (OCT) ndings,
were noted. A literature review of the causes of spontaneous retinal hemorrhages was conducted by searching PubMed using the following keywords: retinal
hemorrhages, macular hemorrhages, and unilateral
spontaneous retinal hemorrhages. References that were
relevant for this case series were reviewed.

Results
Available patients demographic and clinical features are summarized in Table 1. This was limited
by the retrospective nature of the study. Eleven eyes
of 10 patients showed spontaneous, unilateral, predominantly deep intraretinal hemorrhages. All were
women. Five right eyes and six left eyes were affected.
Nine of the 10 patients had no prodromal illness or
history of any other systemic condition related to their
symptoms. One patient (Patient 2) was 6 weeks postpartum when she developed the symptoms but denied
any complications during pregnancy. She had undergone a planned cesarean section, with no labor.
The patients noted sudden unilateral loss of central
vision. The visual acuity was recorded as 20/20 to
hand motion (the patient with hand motion had CF
vision on immediate follow-up). All patients demonstrated multiple deep intraretinal hemorrhages in the
posterior pole. Eight eyes also showed a few supercial hemorrhages and one case (Patient 6) had a small
vitreous hemorrhage at presentation. On clinical
examination and photographs, minimal venous dilation compared with the fellow eye was evident in 5 of

11 eyes. However, the fundus appearance was not felt

to be compatible with a central retinal vein occlusion.
Slit-lamp examination in all cases was normal.
Fluorescein angiography done in 10 of 11 eyes
showed a normal transit in 7 eyes and a possible
delayed retinal arteriovenous transit time in 4 eyes.
The angiograms were otherwise normal. No cases
demonstrated leakage from retinal vessels. Hypouorescence because of blockage from hemorrhages in the
retina was seen in all cases.
Spectral domain OCT was performed in only one
eye (Patient 1). The other patients were seen before the
availability of OCT. The scan showed retinal thickening in areas of hemorrhage with evidence of possible
subretinal uid or hemorrhage at the edge of the retinal
hemorrhage.
With follow-up available on eight patients (nine
eyes), all showed progressive improvement in their
visual acuity, with a near-complete recovery of their
vision, in conjunction with resolution of the intraretinal hemorrhages. This improvement was prominent
by 3 months to 4 months follow-up. One patient
(Patient 1), because of an uncertain diagnosis, received
a short course of systemic corticosteroids and a posterior sub-Tenon triamcinolone injection, without notable change in the evolution of her condition. The
others were not treated. All 9 eyes with follow-up had
a nal visual acuity of 20/50 or better.
No recurrences in the involved eye were observed
during the follow-up. One patient showed involvement
of the second eye (Patient 5) ve years later with the
same clinical and angiographic features. Laboratory
studies (Table 2) performed in variable numbers of
the subjects included a complete blood count, glucose
tolerance test, erythrocyte sedimentation rate, prothrombin time, lipid prole, partial thromboplastin
time, anticardiolipin antibodies, antinuclear antibodies,

Table 1. Demographic Data and Clinical Features of the Patients at Presentation

Age
Patient (Years)/Sex Eye

Initial
Vision

Supercial
Heme

Deep
Heme

Delay Transit
(FA)

Final
Vision

Follow-up
(Months)

Medical Hx

1
2
3
4
5A
5B
6
7
8
9
10

HM
20/400
20/400
20/400
20/20
20/25
20/50
20/200
20/25
N/A
20/40

No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
No

Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

Yes
Yes
No
No
Yes
No
No
No
Yes
No
No

20/40
NR
20/25
20/50
20/20
20/25
20/40
20/40
20/20
20/20
NR

9
N/A
4
5
84
3
72
5
4
4
N/A

Sinusitis
Postpartum
None
None
None
None
None
None
None
None
None

44/F
29/F
52/F
69/F
34/F
39/F
67/F
83/F
53/F
25/F
28/F

OD
OD
OS
OS
OS
OD
OD
OS
OS
OS
OD

F, female; FA, uorescein angiogram; Heme, hemorrhages; HM, hand motion; Hx, history; N/A, not applicable; NR, not recorded; OD,
right eye; OS, left eye.

HEMORRHAGIC RETINOPATHY  KON GRAVERSEN ET AL

485

Table 2. Systemic Results Available in Our Patients

Patients
Number*
1
2
4
5

Workup Performed
CBC, Chemistry 7, ESR, FTA-ABS, VDRL,
HIV, PPD, Factor V, Protein C, Protein S,
Sickle cell screen, Homocysteine,
CBC, Chemistry 7, PT, PTT, ANA, ESR,
VDRL, Magnetic resonance brain, serum
viscosity, C reactive protein
CBC, ESR, Magnetic resonance brain.
CBC, ESR, ANA

*The remaining patients were evaluated by their primary care

physician who performed an unknown workup but were considered healthy.
ANA, antinuclear antibody; CBC, complete blood count; ESR,
erythrocyte sedimentation rate; FTA-ABS, uorescent treponemal
antibody absorption; PPD, puried protein derivative: Tuberculin
sensitivity test; PT, prothrombin time; PTT, partial thromboplastin
time; VDRL, venereal disease research laboratory.

thyroid function, venereal disease research laboratory,

uorescent treponemal antibody absorption, hypercoagulability, and serum chemistry panels. Additional
hematological and radiological investigations were
performed on some patients based on the individual
histories. One patient (Patient 1) showed increased
erythrocyte sedimentation rate at 46 mm/hour (normal
range, ,20 mm/hour), another patient (Patient 2) presented with serum viscosity minimally elevated at 2.0
(normal range, 1.51.9). The systemic workup in
another patient (Patient 5) revealed a weekly positive
antinuclear antibody, without any other abnormal test.
The remaining patients had normal evaluations elsewhere without details available, but all patients were
said to be in excellent health. No patient developed
additional ocular or systemic disease in follow-ups
ranging up to 84 months (Table 1).

Fig. 1. Right eye of Patient 1 at initial presentation. Color fundus photograph showing large deep intraretinal hemorrhages in the posterior pole and
superonasally. At the temporal edge, we can see a halo because of bending
of the retina (arrow). Corrugations are seen within the hemorrhagic area.

The foveal center was unaffected. The left eye fundus

was normal.
Fluorescein angiogram (Figure 2) showed blockage
because of the hemorrhage with no leakage. Optical
coherence tomography was performed conrming retinal thickening, thought to be because of intraretinal
hemorrhage, and the presence of possible subretinal
uid or hemorrhage at the temporal edge of the blood
(Figure 3A). The thickened retina attenuated the signal
for the outer retina (Figure 3B).

Selected Case Reports

Patient 1. A 44-year-old African American woman
was referred for evaluation of a retinal hemorrhage.
She had a 6-day history of acute visual loss in the right
eye. She described an enlarging scotoma in her central
vision for 2 days.
Visual acuity was recorded in the chart as hand
motion in the right eye, with no improvement with
pinhole. The left eye was 20/20. Anterior segment
examination was unremarkable. Intraocular pressures
were normal. Dilated fundus evaluation demonstrated
multiple coalescent deep intraretinal hemorrhages in
the posterior pole, striations were briey visible in the
hemorrhage, probably corresponding to folds of the
thickened retina. Subretinal uid or hemorrhage was
visible at the edges of the retinal hemorrhage (Figure 1).

Fig. 2. Fluorescein angiogram in Patient 1 at presentation showing

blockage because of hemorrhage with no leakage in the fovea.

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RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2014  VOLUME 34  NUMBER 3

Fig. 3. Spectral domain OCT

of the right eye of Patient 1 at
presentation. A. The thickening
involves all the layers of the
outer retina with possible subretinal uid or hemorrhage at
the temporal edge of the retinal
hemorrhage (white arrows). B.
Thickening of the outer layers
of the nasal retina (black
arrows).

A medical workup included complete blood count,

erythrocyte sedimentation rate, uveitis, and hypercoagulability panel. All the results were normal but for
erythrocyte sedimentation rate, which was 46 mm per
hour. The patient specically denied rigorous sexual
activity or Valsalva maneuver.
At 1-month follow-up, the visual acuity was counting ngers. Most of the intraretinal hemorrhages had
cleared, but residual blood had moved toward the
macula and accumulated in the outer plexiform layer

Fig. 4. Spectral domain OCT

of Patient 1 at 1 month:
Clearing of most of the hemorrhages
with
transient
appearance of cystic spaces in
the fovea. There was no leakage on angiography.

(Figure 4). Cystic spaces were seen in the OCT, but no

petaloid leakage was present in the late phases of the
uorescein angiogram. Six months after the initial
event, the hemorrhages had resolved completely, the
OCT was normal, and the visual acuity had improved
to 20/40. The patient was followed for 9 months, and
no systemic or ocular conditions had developed.
Patient 3. A 52-year-old woman presented with
sudden loss of vision in her left eye (Figure 5, picture
also in Reference 2). Her medical history was

HEMORRHAGIC RETINOPATHY  KON GRAVERSEN ET AL

Fig. 5. Clinical picture of Patient 3 at presentation: Color fundus

photograph of left eye with multiple intraretinal hemorrhages, supercial and deep, in the posterior pole.

unremarkable. Visual acuity on presentation was 20/

400 in the left eye and 20/30 in her right eye. Anterior
segment examination and intraocular pressures were
normal. Fundus examination showed multiple deep
and supercial medium and large intraretinal hemorrhages scattered throughout the posterior pole of the
left eye. No venous dilation was observed. The periphery was free of hemorrhage. Fundus examination of
the right eye was normal. Fluorescein angiogram
showed blockage of the uorescein without delay in
the transit time or leakage.
There was no history of trauma to the head or body
and no Valsalva maneuver. Medical evaluation
showed no systemic diseases. Four weeks later, the
patients visual acuity had improved to 20/30. After
4 months of follow-up, her vision was 20/25 in the left
eye, and she remained in excellent health.

Discussion
The denitive cause of the unilateral multiple intraretinal hemorrhages (Figure 6) in these 11 eyes is
unknown. Our 10 healthy mostly young women had
a history of sudden monocular loss of central vision.
Whether these cases had mild transient venous occlusive
disease is not clear. Five of 11 eyes showed slight venous
dilation, and 4 of the 10 eyes that had uorescein angiography had a sluggish A-V transit on the angiographic
study. The longest follow-up was 7 years. None of our
patients had a history of systemic illness to explain the
event. There was no history of physical exertion, Valsalva maneuver, or trauma. There was no ocular inammation, and the fellow eyes were normal. The predilection
for the female gender has no obvious explanation.

487

Several previous reports have described small

macular hemorrhages with no identiable cause, but
these do not resemble our patients. Pruett et al3
reported 20 patients with small monocular macular
hemorrhages that were punctate and round. Some
patients were found to have had Valsalva episodes,
and several others had impaired blood platelet aggregation. The macular microhemorrhages resolved
spontaneously. Messmer et al4 reported 30 cases of
unilateral solitary intraretinal macular hemorrhages
with no evidence of any associated retinal vascular
disease. The lesions were small and solitary, and there
was resolution of most hemorrhages within 2 months
with complete recovery of visual acuity. Pitta et al5
reported retinal hemorrhages in nine patients ranging
from ages 18 years to 47 years. Hemorrhages were
primarily located in the foveal or perifoveal area and
varied in size from a punctate spot to one-half disk
diameter. Four patients had a history of strenuous
exercise, most often weight lifting. Complete resolution of the hemorrhages with excellent recovery of
visual acuity was observed during a period of 2 weeks
to 6 months. The size of the hemorrhages and the link
to Valsalva maneuver or strenuous exercise differed
from the present series.
Spontaneous development of retinal hemorrhages
has also been reported by Oosterhuis6 and Streicher
and Spirkova.7 The evolution was similar to the
patients in our report, however in Oosterhuis series,
physical exertion was felt to be a factor in two patients.
Streicher and Spirkova found Valsalva maneuver as
a possible pathogenic mechanism in three cases.
Duane8 described in detail the pathophysiology of
the retinal response to alterations of the arterial and/
or venous homeostasis by distant trauma. Valsalva
retinopathy is produced by a backward venous vasculopathy, whose clinical manifestations will depend on
the magnitude of the compressive force and the state
of the retinal vessels.8 In the present series, no history
of a Valsalva episode was obtained in any of the cases,
and the clinical features in our patients differ from
Valsalva retinopathy. Most cases of Valsalva retinopathy show a predominance of supercial hemorrhages,
including preretinal hemorrhages. Our patients had
a predominance of deep hemorrhages suggesting their
origin in the deeper layers of the retinal vasculature.
Friberg et al9 presented six cases of a precipitous
unilateral decrease in vision with no apparent predisposing factors. The only common factor was rigorous
sexual activity immediately before the event. In
this series, the authors found intraretinal, preretinal,
and vitreous hemorrhages. The rupture of retinal
blood vessels or an induced retinal tear was the proposed mechanism. All patients experienced good

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RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2014  VOLUME 34  NUMBER 3

Fig. 6. Photographic summary of clinical presentation.

visual recovery. The clinical picture was dissimilar

from our cases, and our Patient 1 specically denied
unusual sexual exertion. In addition, the size of the
intraretinal hemorrhages in our series was larger.
There are many reports of retinal hemorrhages in
mountain climbers.1012 High altitude retinopathy is a signicant component and a predictor of progressive altitude illness. Retinal hemorrhages can be seen because of
elevation of the vascular hydrostatic pressure.13 Familial
retinal arteriolar tortuosity may be associated with spontaneous retinal hemorrhages.14 These pathophysiologic
mechanisms were not found in the present series.
Shaken adult syndrome represents an adult form of
shaken baby syndrome. It consists of the same triad:
bilateral retinal hemorrhages, subdural hematomas,
and patterned bruising in the setting of domestic

violence. All our cases denied previous physical

trauma, and the absence of focal neurological signs
and bruising, plus the unilateral presentation of the
retinal hemorrhages, make this diagnosis unlikely.15,16
Gass2 proposed that in cases of Terson syndrome,
a hemorrhagic maculopathy may develop. He also
described a hemorrhagic maculopathy caused by subarachnoid and epidural injections. These patients have
preretinal and/or vitreous hemorrhage, and the condition is usually bilateral. The primary causative feature
is spontaneous or trauma-induced intracranial bleeding
with secondary acute retinal venous obstruction. None
of our patients had spinal injections. Our series
showed unilaterality in all patients, the predominance
of deep retinal hemorrhages, and no history of trauma
or intracranial process was present.

HEMORRHAGIC RETINOPATHY  KON GRAVERSEN ET AL

The intraretinal hemorrhages reported in this study

differ from previously described entities in several
ways. The hemorrhages were multiple, predominantly
deep, and larger in size. Surprisingly, the retinal
vasculature was relatively uninvolved with mild
venous dilation observed in ve cases only. The
picture was not suggestive of central vein occlusion.
No macular edema was observed. Resolution of the
hemorrhage and recovery of the vision was nearly
complete in the nine eyes with follow-up. Fluorescein
angiogram did not show disk leakage, leakage associated with the hemorrhages, or capillary closure.
Because of the retrospective collection of data, we
cannot with certainty rule out atypical presentations of
the known entities described above. However, because
the etiology of the hemorrhages in these cases was not
found, we suggest the name Hemorrhagic Unilateral
Retinopathy.
Key words: unilateral, intraretinal, hemorrhages.
References
1. Albert DM, Jakobiec FA. Principles and Practice of Ophthalmology. Vol 2. Philadelphia, PA: Saunders WB; 1994.
2. Gass JDM. Chapter 8: Traumatic retinopathy. Retinal and
vitreous hemorrhage associated with subarachnoid and subdural hemorrhages (Tersons syndrome). In: Gasss Atlas of
Macular Diseases. 5th ed. Elsevier; 2012:724727.
3. Pruett RC, Carvalho AC, Trempe CL. Microhemorrhagic maculopathy. Arch Ophthalmol 1981;99:425432.

489

4. Messmer EP, Wessing A, Ruprecht K, Naumann GO. Solitary

intraretinal macular hemorrhage. Graefes Arch Clin Exp Ophthalmol 1984;222:912.
5. Pitta CG, Steinert RF, Gragoudas ES, Regan CD. Small unilateral foveal hemorrhages in young adults. Am J Ophthalmol
1980;89:96102.
6. Oosterhuis JA. Spontaneous retinal hemorrhages. Duane Trans
Am Ophthalmol Soc 1972;70:298313.
7. Streicher T, Spirkova J. Spontaneous premacular hemorrhage
[in Slovak]. Cesk Slov Oftalmol 2008;64:6267.
8. Duane TD. Valsalva hemorrhagic retinopathy. Trans Am Ophthalmol Soc 1972;70:298.
9. Friberg TR, Braunstein RA, Bressler NM. Sudden visual loss
associated with sexual activity. Arch Ophthalmol 1995;113:
738742.
10. Wiedman M. High altitude retinal hemorrhage. Arch Ophthalmol 1975;93:401403.
11. Munsen RS, Blodi FC. High-altitude retinal hemorrhages.
JAMA 1981;245:610.
12. Lubin JR, Rennie D, Hackett P, Albert DM. High altitude
retinal hemorrhage: a clinical pathological case report. Ann
Ophthalmol 1982;14:10711076.
13. Rabinovitch P, McLean EB, Beck GR, Brown AC. Recurrent
pre retinal hemorrhages following a negative g maneuver
on school playground equipment. J Pediatr 1978;92:
846847.
14. Goldberg MF, Pollack IP, Green RW. Familiar retinal arteriolar tortuosity with retinal hemorrhage. Am J Ophthalmol 1972;
73:183191.
15. Pounder DJ. Shaken adult syndrome. Am J Forensic Med
Pathol 1997;18:321324.
16. Carrigan T, Walker E, Barnes S. Domestic violence: the
shaken adult syndrome. J Accid Emerg Med 2000;17:
138139.