hemorrhagic unilateral retinopathy

8/18/2019 Hemorrhagic Unilateral Retinopathy

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HEMORRHAGIC UNILATERALRETINOPATHY

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, 25–83 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 34:483–489, 2014

Intraretinal hemorrhages may develop as a result of a large number of ocular and systemic conditions,

including anemia, coagulopathies, hyperviscosity, leu-

kemias, vascular occlusive disease, hypertension, dia-betes, and ocular neovascularization.

1Small unilateral

hemorrhages in the posterior pole have been previ-ously reported in young adults.2–6 The occurrence of retinal hemorrhages in otherwise healthy people has

also been documented after blunt trauma, Valsalva maneuver,7,8 extreme physical exertion, sexual activ-ity,

9exposure to high altitudes,

10–12 stress because of the elevation of vascular hydrostatic pressure at eyelevel,13 patients with genetic predisposition,14 and shaken

adult syndrome.15,16 In some cases, no etiology couldbe identied.

The constellation of ndings in the 11 eyes of our

patients revealed spontaneous, predominantly deep,unilateral intraretinal hemorrhages. These deep hem-orrhages were larger in size than previously reportedspontaneous hemorrhages. No systemic or ocular conditions were identied. The clinical course was

a resolution of the hemorrhages and near-completerecovery of vision in eight patients (nine eyes) with

available follow-up. This report describes the clinicaland imaging features and outcomes of this entity withdiscussion of the differential diagnosis.

Patients and Methods

In 1996, during a Retina meeting, Maurice Rabb,MD, presented a young healthy patient with anunusual pattern of deep intraretinal hemorrhages andno ocular or systemic diseases. Subsequent to thepresentation, several retinal specialists brought for-

ward similar cases. Dr. Rabb categorized these cases.Recently, we encountered an identical patient and haveretrospectively analyzed these cases and reviewed theliterature. We collected 11 eyes of 10 patients with

From the *Department of Ophthalmology, University of NorthCarolina 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 todisclose.

Supported in part by unrestricted grants from Research to Prevent Blindness, Inc, New York, NY (Northwestern University/Universityof 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: [email protected]

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a mean age of 48.4 years (range, 25–83 years). Demo-graphic information, preexisting conditions, medica-tions, and details of the initial and nal examinations,

including visual acuity, intraocular pressure, angiogra-phy, and optical coherence tomography (OCT) ndings,

were noted. A literature review of the causes of spon-

taneous retinal hemorrhages was conducted by search-ing PubMed using the following keywords: retinalhemorrhages, macular hemorrhages, and unilateralspontaneous retinal hemorrhages. References that were

relevant for this case series were reviewed.

Results

Available patients’ demographic and clinical fea-

tures are summarized in Table 1. This was limitedby the retrospective nature of the study. Eleven eyes

of 10 patients showed spontaneous, unilateral, pre-dominantly deep intraretinal hemorrhages. All werewomen. 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 post-partum when she developed the symptoms but deniedany complications during pregnancy. She had under-gone a planned cesarean section, with no labor.

The patients noted sudden unilateral loss of centralvision. The visual acuity was recorded as 20/20 tohand motion (the patient with hand motion had CF

vision on immediate follow-up). All patients demon-strated multiple deep intraretinal hemorrhages in theposterior pole. Eight eyes also showed a few super -

cial hemorrhages and one case (Patient 6) had a smallvitreous hemorrhage at presentation. On clinicalexamination and photographs, minimal venous dila-tion 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 eyesshowed a normal transit in 7 eyes and a possibledelayed retinal arteriovenous transit time in 4 eyes.

The angiograms were otherwise normal. No casesdemonstrated leakage from retinal vessels. Hypouor-escence because of blockage from hemorrhages in theretina was seen in all cases.

Spectral domain OCT was performed in only oneeye (Patient 1). The other patients were seen before theavailability of OCT. The scan showed retinal thicken-ing in areas of hemorrhage with evidence of possiblesubretinal uid or hemorrhage at the edge of the retinalhemorrhage.

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 intra-retinal 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 poste-rior sub-Tenon triamcinolone injection, without nota-ble change in the evolution of her condition. Theothers 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 thesame clinical and angiographic features. Laboratorystudies (Table 2) performed in variable numbers of the subjects included a complete blood count, glucose

tolerance test, erythrocyte sedimentation rate, pro-thrombin time, lipid prole, partial thromboplastintime, anticardiolipin antibodies, antinuclear antibodies,

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

Patient Age

(Years)/Sex EyeInitial

VisionSuper cial

HemeDeepHeme

Delay Transit(FA)

Final Vision

Follow-up(Months) Medical Hx

1 44/F OD HM No Yes Yes 20/40 9 Sinusitis2 29/F OD 20/400 Yes Yes Yes NR N/A Postpartum3 52/F OS 20/400 Yes Yes No 20/25 4 None4 69/F OS 20/400 Yes Yes No 20/50 5 None5A 34/F OS 20/20 Yes Yes Yes 20/20 84 None5B 39/F OD 20/25 Yes Yes No 20/25 3 None6 67/F OD 20/50 Yes Yes No 20/40 72 None7 83/F OS 20/200 Yes Yes No 20/40 5 None8 53/F OS 20/25 No Yes Yes 20/20 4 None9 25/F OS N/A Yes Yes No 20/20 4 None

10 28/F OD 20/40 No Yes No NR N/A None

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.

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thyroid function, venereal disease research laboratory,uorescent treponemal antibody absorption, hyperco-agulability, and serum chemistry panels. Additionalhematological and radiological investigations wereperformed on some patients based on the individualhistories. One patient (Patient 1) showed increased

erythrocyte sedimentation rate at 46 mm/hour (normalrange, ,20 mm/hour), another patient (Patient 2) pre-sented with serum viscosity minimally elevated at 2.0(normal range, 1.5–1.9). The systemic workup inanother patient (Patient 5) revealed a weekly positiveantinuclear antibody, without any other abnormal test.

The remaining patients had normal evaluations else-where without details available, but all patients weresaid to be in excellent health. No patient developedadditional ocular or systemic disease in follow-upsranging up to 84 months (Table 1).

Selected Case Reports

Patient 1. A 44-year-old African American womanwas 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 centralvision for 2 days.

Visual acuity was recorded in the chart as handmotion in the right eye, with no improvement withpinhole. The left eye was 20/20. Anterior segment examination was unremarkable. Intraocular pressureswere normal. Dilated fundus evaluation demonstratedmultiple coalescent deep intraretinal hemorrhages in

the posterior pole, striations were briey visible in thehemorrhage, probably corresponding to folds of thethickened retina. Subretinal uid or hemorrhage wasvisible at the edges of the retinal hemorrhage (Figure 1).

The foveal center was unaffected. The left eye funduswas normal.

Fluorescein angiogram (Figure 2) showed blockagebecause of the hemorrhage with no leakage. Optical

coherence tomography was performed conrming ret-inal thickening, thought to be because of intraretinalhemorrhage, and the presence of possible subretinaluid or hemorrhage at the temporal edge of the blood(Figure 3A). The thickened retina attenuated the signalfor the outer retina (Figure 3B).

Table 2. Systemic Results Available in Our Patients

Patient’sNumber* Workup Performed

1 CBC, Chemistry 7, ESR, FTA-ABS, VDRL,HIV, PPD, Factor V, Protein C, Protein S,Sickle cell screen, Homocysteine,

2 CBC, Chemistry 7, PT, PTT, ANA, ESR, VDRL, Magnetic resonance brain, serumviscosity, C reactive protein

4 CBC, ESR, Magnetic resonance brain.5 CBC, ESR, ANA

*The remaining patients were evaluated by their primary carephysician who performed an unknown workup but were consid-ered healthy.

ANA, antinuclear antibody; CBC, complete blood count; ESR,erythrocyte sedimentation rate; FTA-ABS, uorescent treponemalantibody absorption; PPD, puried protein derivative: Tuberculinsensitivity test; PT, prothrombin time; PTT, partial thromboplastintime; VDRL, venereal disease research laboratory.

Fig. 1. Right eye of Patient 1 at initial presentation. Color fundus photo-graph showing large deep intraretinal hemorrhages in the posterior pole andsuperonasally. At the temporal edge, we can see a “halo” because of bendingof the retina (arrow). Corrugations are seen within the hemorrhagic area.

Fig. 2. Fluorescein angiogram in Patient 1 at presentation showingblockage because of hemorrhage with no leakage in the fovea.

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A medical workup included complete blood count,erythrocyte sedimentation rate, uveitis, and hypercoag-

ulability 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 count-

ing ngers. Most of the intraretinal hemorrhages had

cleared, but residual blood had moved toward the

macula and accumulated in the outer plexiform layer

(Figure 4). Cystic spaces were seen in the OCT, but nopetaloid leakage was present in the late phases of the

uorescein angiogram. Six months after the initialevent, the hemorrhages had resolved completely, theOCT was normal, and the visual acuity had improvedto 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, picturealso in Reference 2). Her medical history was

Fig. 3. Spectral domain OCTof the right eye of Patient 1 at presentation. A. The thickening

involves all the layers of theouter retina with possible sub-retinal uid or hemorrhage at the temporal edge of the retinalhemorrhage (white arrows). B.Thickening of the outer layersof the nasal retina (black arrows).

Fig. 4. Spectral domain OCTof Patient 1 at 1 month:Clearing of most of the hem-orrhages with transient appearance of cystic spaces inthe fovea. There was no leak-age on angiography.



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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 deepand super cial medium and large intraretinal hemor-rhages scattered throughout the posterior pole of theleft eye. No venous dilation was observed. The periph-

ery was free of hemorrhage. Fundus examination of the right eye was normal. Fluorescein angiogram

showed blockage of the uorescein without delay inthe transit time or leakage.

There was no history of trauma to the head or bodyand no Valsalva maneuver. Medical evaluation

showed no systemic diseases. Four weeks later, thepatient ’s 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 intra-retinal hemorrhages (Figure 6) in these 11 eyes isunknown. Our 10 healthy mostly young women hada history of sudden monocular loss of central vision.

Whether these cases had mild transient venous occlusivedisease is not clear. Five of 11 eyes showed slight venousdilation, and 4 of the 10 eyes that had uorescein angi-ography had a sluggish A-V transit on the angiographicstudy. 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, Valsal-va maneuver, or trauma. There was no ocular inamma-tion, and the fellow eyes were normal. The predilectionfor the female gender has no obvious explanation.

Several previous reports have described smallmacular 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 aggre-gation. The macular microhemorrhages resolvedspontaneously. 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 therewas resolution of most hemorrhages within 2 monthswith complete recovery of visual acuity. Pitta et al5

reported retinal hemorrhages in nine patients rangingfrom ages 18 years to 47 years. Hemorrhages were

primarily located in the foveal or perifoveal area andvaried in size from a punctate spot to one-half disk

diameter. Four patients had a history of strenuousexercise, most often weight lifting. Complete resolu-tion 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 differedfrom the present series.

Spontaneous development of retinal hemorrhageshas also been reported by Oosterhuis6 and Streicher

and Spirkova.7

The evolution was similar to thepatients in our report, however in Oosterhuis’ series,

physical exertion was felt to be a factor in two patients.

Streicher and Spirkova found Valsalva maneuver asa 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 vascul-opathy, whose clinical manifestations will depend onthe magnitude of the compressive force and the stateof 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 retinop-athy show a predominance of super cial hemorrhages,including preretinal hemorrhages. Our patients hada predominance of deep hemorrhages suggesting their origin in the deeper layers of the retinal vasculature.

Friberg et al9

presented six cases of a precipitousunilateral decrease in vision with no apparent predis-posing factors. The only common factor was rigoroussexual activity immediately before the event. In

this series, the authors found intraretinal, preretinal,and vitreous hemorrhages. The rupture of retinalblood vessels or an induced retinal tear was the pro-posed mechanism. All patients experienced good

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

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



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visual recovery. The clinical picture was dissimilar

from our cases, and our Patient 1 specically deniedunusual sexual exertion. In addition, the size of theintraretinal hemorrhages in our series was larger.

There are many reports of retinal hemorrhages inmountain climbers.10–12 High altitude retinopathy is a sig-

nicant component and a predictor of progressive alti-tude illness. Retinal hemorrhages can be seen because of elevation of the vascular hydrostatic pressure.

13Familial

retinal arteriolar tortuosity may be associated with spon-taneous retinal hemorrhages.14 These pathophysiologicmechanisms 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 signsand bruising, plus the unilateral presentation of theretinal 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 sub-arachnoid and epidural injections. These patients havepreretinal and/or vitreous hemorrhage, and the condi-tion is usually bilateral. The primary causative featureis spontaneous or trauma-induced intracranial bleedingwith secondary acute retinal venous obstruction. None

of our patients had spinal injections. Our seriesshowed unilaterality in all patients, the predominanceof deep retinal hemorrhages, and no history of trauma or intracranial process was present.

Fig. 6. Photographic summary of clinical presentation.



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The intraretinal hemorrhages reported in this studydiffer from previously described entities in severalways. The hemorrhages were multiple, predominantly

deep, and larger in size. Surprisingly, the retinalvasculature 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 thehemorrhage and recovery of the vision was nearlycomplete in the nine eyes with follow-up. Fluorescein

angiogram did not show disk leakage, leakage asso-ciated with the hemorrhages, or capillary closure.

Because of the retrospective collection of data, wecannot with certainty rule out atypical presentations of the known entities described above. However, becausethe etiology of the hemorrhages in these cases was not

found, we suggest the name Hemorrhagic UnilateralRetinopathy.

Key words: unilateral, intraretinal, hemorrhages.

References

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ulopathy. Arch Ophthalmol 1981;99:425–432.

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

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10. Wiedman M. High altitude retinal hemorrhage. Arch Ophthal-

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11. Munsen RS, Blodi FC. High-altitude retinal hemorrhages.

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12. Lubin JR, Rennie D, Hackett P, Albert DM. High altitude

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Ophthalmol 1982;14:1071–1076.

13. Rabinovitch P, McLean EB, Beck GR, Brown AC. Recurrent

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Pathol 1997;18:321–324.

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