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Figure 1.
Patient 29, an 80-year-old man. A, Fundus photograph at initial examination, with decreased visual acuity (20/200) secondary to macular hemorrhage caused by rupture of a retinal artery macroaneurysm. The posterior segment examination showed subretinal and preretinal hemorrhage involving the macula. B, Fluorescein angiogram demonstrated filling of the macroaneurysm with dye and adjacent blockage resulting from the presence of subretinal blood. C, Thirteen months after initial examination, the macular hemorrhage has completely resolved without residual pigmentary changes and the visual acuity returned to 20/30.

Patient 29, an 80-year-old man. A, Fundus photograph at initial examination, with decreased visual acuity (20/200) secondary to macular hemorrhage caused by rupture of a retinal artery macroaneurysm. The posterior segment examination showed subretinal and preretinal hemorrhage involving the macula. B, Fluorescein angiogram demonstrated filling of the macroaneurysm with dye and adjacent blockage resulting from the presence of subretinal blood. C, Thirteen months after initial examination, the macular hemorrhage has completely resolved without residual pigmentary changes and the visual acuity returned to 20/30.

Figure 2.
Patient 28, a 75-year-old woman. A, Fundus photograph at initial examination, with visual acuity of counting fingers with eccentric fixation and a large hemorrhage in the macula from a ruptured retinal artery macroaneurysm. B, Appearance 16 months after initial examination; the blood cleared in 5 months and visual acuity had slowly returned to 20/25.

Patient 28, a 75-year-old woman. A, Fundus photograph at initial examination, with visual acuity of counting fingers with eccentric fixation and a large hemorrhage in the macula from a ruptured retinal artery macroaneurysm. B, Appearance 16 months after initial examination; the blood cleared in 5 months and visual acuity had slowly returned to 20/25.

Figure 3.
Patient 36, a 79-year-old woman. A, Fundus photograph after sudden decrease in visual acuity of the right eye to hand motions. The posterior segment examination showed subretinal and preretinal hemorrhage involving the macula. B, Fluorescein angiogram showing filling of a retinal artery macroaneurysm with dye. Blood under the neurosensory retina blocks fluorescence around the macroaneurysm. Because of overlying preretinal hemorrhage, the extent of the subretinal hemorrhage cannot be determined with certainty. C, Appearance 8 months later; the macroaneurysm has undergone fibrosis, the hemorrhage has cleared, and the visual acuity has returned to 20/70.

Patient 36, a 79-year-old woman. A, Fundus photograph after sudden decrease in visual acuity of the right eye to hand motions. The posterior segment examination showed subretinal and preretinal hemorrhage involving the macula. B, Fluorescein angiogram showing filling of a retinal artery macroaneurysm with dye. Blood under the neurosensory retina blocks fluorescence around the macroaneurysm. Because of overlying preretinal hemorrhage, the extent of the subretinal hemorrhage cannot be determined with certainty. C, Appearance 8 months later; the macroaneurysm has undergone fibrosis, the hemorrhage has cleared, and the visual acuity has returned to 20/70.

Figure 4.
Patient 5, a 76-year-old woman. A, Fundus photograph obtained after sudden decrease in visual acuity (1/400) secondary to a macular hemorrhage from a ruptured retinal artery macroaneurysm. B, Appearance 14 months later; the blood has cleared and the visual acuity has returned to 20/40.

Patient 5, a 76-year-old woman. A, Fundus photograph obtained after sudden decrease in visual acuity (1/400) secondary to a macular hemorrhage from a ruptured retinal artery macroaneurysm. B, Appearance 14 months later; the blood has cleared and the visual acuity has returned to 20/40.

Figure 5.
Patient 12, an 86-year-old woman. A, Fundus photograph at initial examination; visual acuity is 20/200 and macular hemorrhage is present from a ruptured macroaneurysm. The blood cleared in 5 months. B, Appearance 11 months after the initial hemorrhage; the visual acuity is 20/100 and pigmentary changes are noted in the area of previous subretinal blood.

Patient 12, an 86-year-old woman. A, Fundus photograph at initial examination; visual acuity is 20/200 and macular hemorrhage is present from a ruptured macroaneurysm. The blood cleared in 5 months. B, Appearance 11 months after the initial hemorrhage; the visual acuity is 20/100 and pigmentary changes are noted in the area of previous subretinal blood.

Figure 6.
Patient 23, a 68-year-old man. A, Fundus photograph obtained after the patient noted a sudden decrease in visual acuity (to 20/400) in his left eye secondary to a retinal artery macroaneurysm with a large subretinal hemorrhage involving the fovea. A small preretinal hemorrhage is present overlying the macroaneurysm. B, Appearance 4 months later. The hemorrhage has resolved; however, extensive pigmentary change is seen within the macular region and visual acuity is limited to 20/400.

Patient 23, a 68-year-old man. A, Fundus photograph obtained after the patient noted a sudden decrease in visual acuity (to 20/400) in his left eye secondary to a retinal artery macroaneurysm with a large subretinal hemorrhage involving the fovea. A small preretinal hemorrhage is present overlying the macroaneurysm. B, Appearance 4 months later. The hemorrhage has resolved; however, extensive pigmentary change is seen within the macular region and visual acuity is limited to 20/400.

Table 1. 
Summary of Patient Data
Summary of Patient Data
Table 2. 
Summary of Observational Studies of Submacular Hemorrhage Not Related to Age-Related Macular Degeneration
Summary of Observational Studies of Submacular Hemorrhage Not Related to Age-Related Macular Degeneration
Table 3. 
Summary of Reported Surgical Cases of Submacular Hemorrhage From Retinal Artery Macroaneurysms
Summary of Reported Surgical Cases of Submacular Hemorrhage From Retinal Artery Macroaneurysms
1.
Robertson  DM Macroaneurysms of the retinal arteries. Trans Am Acad Ophthalmol Otolaryngol. 1973;77OP55- OP67
2.
Rabb  MFGagliano  DATeske  MP Retinal arterial macroaneurysms. Surv Ophthalmol. 1988;3373- 96Article
3.
Panton  RWGoldberg  MFFarber  MD Retinal artery macroaneurysms: risk factors and natural history. Br J Ophthalmol. 1990;74595- 600Article
4.
Brown  DMSobol  WMFolk  JCWeingeist  TA Retinal arteriolar macroaneurysms: long term visual outcome. Br J Ophthalmol. 1994;78534- 538Article
5.
Glatt  HMachemer  R Experimental subretinal hemorrhage in rabbits. Am J Ophthalmol. 1982;94762- 773Article
6.
Toth  CAMorse  LSHjelmeland  LMLanders  MB  III Fibrin directs early retinal damage after experimental subretinal hemorrhage. Arch Ophthalmol. 1991;109723- 729Article
7.
Brent  BDGonce  MDiamond  JG Pars plana vitrectomy for complications of retinal arterial macroaneurysms: a case series. Ophthalmic Surg. 1993;24534- 536
8.
Lewis  H Intraoperative fibrinolysis of submacular hemorrhage with tissue plasminogen activator and surgical drainage. Am J Ophthalmol. 1994;118559- 568
9.
Ibanez  HEWilliams  DFThomas  MA  et al.  Surgical management of submacular hemorrhage: a series of 47 consecutive cases. Arch Ophthalmol. 1995;11362- 69Article
10.
Terasaki  HMiyake  YKondo  MTanikawa  A Focal macular electroretinogram before and after drainage of macular subretinal hemorrhage. Am J Ophthalmol. 1997;123207- 211
11.
Saika  SYamanaka  AYamanaka  A  et al.  Subretinal administration of tissue-type plasminogen activator to speed the drainage of subretinal hemorrhage. Graefes Arch Clin Exp Ophthalmol. 1998;236196- 201Article
12.
Kamei  MTano  YMaeno  TIkuno  YMitsuda  HYuasa  T Surgical removal of submacular hemorrhage using tissue plasminogen activator and perfluorocarbon liquid. Am J Ophthalmol. 1996;121267- 275
13.
Lim  JIDrews-Botsch  CSternberg  P  JrCapone  A  JrAaberg Sr  TM Submacular hemorrhage removal. Ophthalmology. 1995;1021393- 1399Article
14.
Wade  ECFlynn  HW  JrOlsen  KRBlumenkranz  MSNicholson  DH Subretinal hemorrhage management by pars plana vitrectomy and internal drainage. Arch Ophthalmol. 1990;108973- 978Article
15.
Homayun  MLewis  HFlynn  HW  JrSternberg  P  JrBlumenkranz  MS Management of submacular hemorrhage associated with retinal artery macroaneurysms. Am J Ophthalmol. 1998;126358- 361Article
16.
Hochman  MASeery  CMZarbin  MA Pathophysiology and management of subretinal hemorrhage. Surv Ophthalmol. 1997;42195- 213Article
17.
Hayasaka  SUchida  MSetogawa  T Subretinal hemorrhages with or without choroidal neovascularization in the maculas of patients with pathologic myopia. Graefes Arch Clin Exp Ophthalmol. 1990;228277- 280Article
18.
Berrocal  MHLewis  MLFlynn  HW  Jr Variations in the clinical course of submacular hemorrhage. Am J Ophthalmol. 1996;122486- 493
19.
Bennett  SRFolk  JCBlodi  CFKlugman  M Factors prognostic of visual outcome in patients with subretinal hemorrhage. Am J Ophthalmol. 1990;10933- 37
20.
Avery  RLFekrat  SHawkins  BSBressler  NM Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina. 1996;16183- 189Article
21.
Zhao  PHayashi  HOshima  KNakagawa  NOhsato  M Vitrectomy for macular hemorrhage associated with retinal artery macroaneurysm. Ophthalmology. 2000;107613- 617Article
22.
Iijima  HSatoh  STsukahara  S Nd:YAG laser photodisruption for preretinal hemorrhage due to retinal macroaneurysm. Retina. 1998;18430- 434Article
23.
Ohji  MSaito  YHayashi  ALewis  JMTano  Y Pneumatic displacement of subretinal hemorrhage without tissue plasminogen activator. Arch Ophthalmol. 1998;1161326- 1332Article
24.
Hassan  ASJohnson  MWSchneiderman  TE  et al.  Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology. 1999;1061900- 1907Article
25.
Heriot  WJ Intravitreal gas and TPA: an outpatient procedure for submacular hemorrhage.  Paper presented at: Vitreoretinal Frontiers October 25, 1996 Chicago, Ill
26.
Johnson  MWOlsen  KRHernandez  EIrvine  WDJohnson  RN Retinal toxicity of recombinant tissue plasminogen activator in the rabbit. Arch Ophthalmol. 1990;108259- 263Article
Clinical Sciences
June 2000

Nonsurgical Management of Macular Hemorrhage Secondary to Retinal Artery Macroaneurysms

Author Affiliations

From the Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Fla (Drs McCabe and Flynn); Departments of Ophthalmology, Pennsylvania State Medical Center, Hershey (Dr Brod), University of California, San Francisco (Dr McDonald), and University of Michigan, Ann Arbor (Dr Johnson); and The Eye Institute, Medical College of Wisconsin, Milwaukee (Dr Mieler). Dr McLean is in private practice in Ashville, NC, and Dr Williams, in Royal Oak, Mich.

Arch Ophthalmol. 2000;118(6):780-785. doi:10.1001/archopht.118.6.780
Abstract

Objective  To report visual acuity outcomes of nonsurgical management of macular hemorrhage secondary to retinal artery macroaneurysms.

Methods  Forty-one patients at multiple centers with macular hemorrhage secondary to retinal artery macroaneurysms managed with observation alone were reviewed. Time to clearance of macular hemorrhage, visual acuity at final follow-up, and presence or absence of macular pigmentary changes after absorption of the hemorrhage were recorded for each patient.

Results  On initial examination, visual acuity was 20/200 or worse in all except 4 patients (3 with 20/70, 1 with 20/80). At an average follow-up of 15.7 months, a final visual acuity of 20/40 or better was achieved in 15 eyes (37%), between 20/50 and 20/100 in 12 (29%), and 20/200 or worse in 14 (34%). Macular pigmentary abnormalities were noted after clearance of the hemorrhage in 23 (56%) of 41 cases, and these eyes generally had worse visual acuity outcomes.

Conclusions  In eyes with macular hemorrhage secondary to retinal artery macroaneurysms managed with observation alone, good visual acuity outcomes can often be achieved. Poorer visual acuity outcomes are associated with macular pigmentary changes after resorption of blood.

SUBMACULAR HEMORRHAGE can result in acute and long-term decreased visual acuity.14 Because the presence of subretinal blood results in early damage to photoreceptors in animal models,5,6 prompt surgical removal of submacular blood has been investigated in an attempt to improve final visual acuity.715 Reported visual acuity outcomes after vitrectomy for submacular hemorrhage have been variable and depend on multiple preoperative, operative, and postoperative factors.816 In general, poorer visual outcomes have been associated with longer duration of subretinal blood before removal, increased thickness of subfoveal blood, and age-related macular degeneration (AMD) as the underlying disease process.1620 However, relatively good visual outcomes have been reported in some patients with observation alone.1620

The current study investigated visual and anatomical outcomes in patients with macular hemorrhage from retinal artery macroaneurysms managed with observation alone.

PATIENTS AND METHODS

The current study included outpatients with macular hemorrhage secondary to a retinal artery macroaneurysm examined at multiple centers (from January 1, 1970, to December 31, 1998) who were managed with observation alone. Approval was obtained from the institutional review board at the University of Miami School of Medicine, Miami, Fla, before initiation of this study, but it was not required at the other participating institutions. Patients with blood involving the fovea from a ruptured macroaneurysm, good prior visual acuity, no marked AMD in the fellow eye (by photographic documentation or office records), at least 2 months of follow-up, and fundus photographs taken at the time of initial examination were included. Patients with marked AMD included patients with loss of vision from AMD as determined by clinical history provided by the patient, photographic documentation, and/or office records. Amblyopic eyes and those with coexisting ocular disease (eg, diabetic retinopathy, AMD) were excluded.

A total of 26 patients were excluded from the study. Of these, 7 patients had visual acuities between 20/30 and 20/50 and only a thin layer of hemorrhage in the foveal region, 1 patient had undergone pars plana vitrectomy, 2 had no follow-up information available, and 4 did not have photographs taken at the time of the initial examination. Twelve patients had been treated with laser photocoagulation at some time during the follow-up period and were excluded from the study; 1 of these patients also had a branch retinal artery occlusion. The data were collected retrospectively from the office records of participating study ophthalmologists. Twenty ophthalmologists in 15 offices were part of the current study.

Best-corrected initial and final Snellen visual acuities were recorded by the individual physician for each patient, although no standardized protocol for measurement of visual acuity was used. Pinhole vision testing was not used. The time to clearance of macular hemorrhage and the presence or absence of any associated pigmentary changes in the macula after resorption of blood were recorded by the participating study ophthalmologist, on the basis of photographic documentation and review of chart notes. In addition, we reviewed all photographs to confirm the presence or absence of macular pigmentary changes.

Initial fundus photographs were reviewed to ascertain the level at which the hemorrhage was located and to verify that the hemorrhage involved the fovea. Although color fundus photographs were reviewed for each case, stereo images or fluorescein angiograms were not available for all patients. In these cases, the tissue level of the hemorrhage had to be estimated by means of available photographs and the office records from the study ophthalmologists. The hemorrhage was often located at several tissue levels within the macula of an individual patient, but a portion of the hemorrhage was located beneath the neurosensory retina in all cases. If hemorrhage was present beneath the internal limiting membrane at the fovea, the extent of the subretinal hemorrhage beneath the fovea could not be verified.

RESULTS

Forty-one eyes of 41 patients met inclusion criteria. Thirty-four (83%) of the patients were women, with an average age of 75.6 years (range, 41 to 93 years). Follow-up time from initial examination to most recent examination ranged from 2 to 87 months, with an average of 15.7 months.

Initial visual acuities ranged from 20/70 to hand motions, with 37 (90%) of 41 eyes having visual acuity of 20/200 or worse at initial examination. All hemorrhages cleared without surgical intervention. Mean time for clearance of subretinal blood was 4.6 months, with a range of 1 to 14 months. Final visual acuity ranged from 20/20 to 5/200. At the last follow-up examination, the visual acuities were 20/40 or better in 15 (37%) of 41 eyes, 20/50 to 20/100 in 12 (29%) of 41, and 20/200 or worse in 14 (34%) of 41 (Table 1).

One patient had a second hemorrhage after resorption of the initial macular hemorrhage. Although visual acuity before rebleeding improved to 20/70, final visual acuity was 20/200 at 19 months after initial examination.

The cause of reduced visual acuity at final follow-up was evaluated. No study patients developed disciform macular scars or had a clinically visible branch retinal artery occlusion. Likewise, no study patients had branch retinal vein occlusion, central retinal vein occlusion, or advanced glaucoma.

Pigmentary abnormalities were present in the macular region after clearance of hemorrhage in approximately half of the patients (23 of 41 cases). Patients without pigmentary changes tended to have a better visual prognosis. Ten (56%) of 18 patients without pigmentary alterations achieved 20/40 or better visual acuity, 4 eyes (22%) achieved 20/50 to 20/100, and 4 eyes (22%) achieved final visual acuity of 20/200 or worse. Fundus photographs and fluorescein angiograms of representative patients without residual pigmentary changes after clearance of macular hemorrhage and with restoration of good visual acuity are shown in Figure 1 and Figure 2. Fundus photographs from a patient with moderate visual acuity improvement after resorption of the hemorrhage without extensive pigmentary changes in the macula are shown in Figure 3.

Visual outcomes in cases with residual pigmentary changes were generally more limited. Of those with macular pigmentary changes, a visual acuity of 20/40 or better was achieved in 5 (22%) of 23 eyes, between 20/50 and 20/100 in 8 (35%), and 20/200 or worse in 10 (43%). Fundus photographs of a representative patient with pigmentary changes after resorption of the hemorrhage and return of good visual acuity are shown in Figure 4. Fundus photographs of representative patients with extensive pigmentary changes and limited final visual acuity are shown in Figure 5 and Figure 6.

COMMENT

The current observational study of macular hemorrhage from a ruptured retinal artery macroaneurysm is the largest reported to date and provides important follow-up data on these patients. However, the results of the current study are limited by the fact that the study is retrospective and was restricted to patients who met the inclusion criteria. Additionally, best-corrected Snellen visual acuities were not obtained according to a standardized protocol, and patients were selected by a review of medical records. Because of controversy regarding the toxicity of submacular hemorrhage and its effect on visual acuity, the current study was initiated to provide visual outcomes in patients with macular hemorrhage when no underlying disease process is present.

In experimental animal studies, marked photoreceptor damage can occur after introduction of subretinal hemorrhage. Chronic retinal damage may result from chemical toxicity, mechanical traction, or barrier effect on diffusion.5,6 In 1982, Glatt and Machemer,5 using a rabbit model, showed that edema and disintegration of the photoreceptors and pyknosis of the outer nuclear layer occur during the first 24 hours of exposure to subretinal blood. In 1991, Toth and associates,6 using a cat model, demonstrated interdigitation of fibrin strands with photoreceptors 1 hour after onset of subretinal hemorrhage. Subsequent contraction of the adjacent fibrin clot resulted in shearing of sheets of photoreceptor outer segments. However, subretinal blebs created with tissue-type plasminogen activator (TPA) included in the solution had no fibrin strand formation or tearing of photoreceptors. Because of the potential for permanent photoreceptor damage, many practitioners advocate prompt removal of subretinal blood located in the macula, often assisted by the use of TPA.

Observational studies of eyes with submacular hemorrhage that used retrospective data collection from patients' medical records have shown that visual outcomes depend on a number of factors, including thickness, size, and location of blood, and underlying cause of the hemorrhage.1620 These studies have shown that patients with submacular hemorrhage from causes other than choroidal neovascularization and AMD can recover good visual acuity with observational management alone (Table 2). Data from the current study confirm that good visual acuity outcomes can be achieved in eyes with macular hemorrhage from rupture of a retinal artery macroaneurysm without surgical intervention.

If the 33 patients with ruptured artery macroaneurysms are separated from reported series of patients with submacular hemorrhage treated surgically, about one third achieved a visual acuity of 20/40 or better, one third had 20/50 to 20/100, and one third had 20/200 or worse at last follow-up examination (Table 3). In a recent vitrectomy study of 8 patients treated with or without TPA, the visual acuity outcomes were generally favorable.21 It is important to recognize that 3 patients in this series had preretinal hemorrhage only. In the current observational study, visual acuity outcomes in 41 eyes with macular hemorrhage from a ruptured retinal artery macroaneurysm managed with observation alone were similar to the surgical outcomes in these 33 reported cases.

Two additional treatment options for management of macular hemorrhage from retinal artery macroaneurysms have been reported.22,23 Six eyes with preretinal hemorrhage involving the macula from a ruptured retinal artery macroaneurysm were treated with Nd:YAG laser photodisruption of the anterior surface of the hemorrhage, allowing drainage of the blood into the vitreous.22 Four of the 6 eyes had both subretinal and preretinal hemorrhage. Visual acuity improved in all cases at 1 week after treatment, but poorer visual acuity outcomes were seen in eyes with subretinal blood.

A second treatment option is pneumatic displacement of macular hemorrhage with or without pretreatment with intravitreal TPA.23,24 In one recent study, 5 patients with subretinal hemorrhage (1 from a retinal artery macroaneurysm and 4 from AMD) were treated with pneumatic displacement of blood without the use of TPA.23 Four of 5 patients were treated within 6 days of the onset of symptoms. Final visual acuity ranged from 20/220 to 20/15; the patient with the macroaneurysm recovered 20/40 visual acuity. Heriot25 reported a similar technique with the addition of intravitreal TPA, but there is a risk of retinal toxic effects from exposure to higher doses of TPA.26 Another pneumatic displacement study reported 15 patients treated for submacular hemorrhage caused by AMD.24 Although the hemorrhage was displaced in all patients, complications included vitreous hemorrhage in 3 patients and endophthalmitis in 1 patient.

In the current study, the majority of patients (56%) had some degree of pigmentary changes in the macula after clearance of macular hemorrhage. A trend toward poorer visual acuity outcomes was noted in patients with pigmentary changes compared with those without these changes. These areas of pigmentary change may represent more extensive damage to the neurosensory retina and retinal pigment epithelium in areas with increased thickness of the subretinal portion of the hemorrhage. Further follow-up is necessary to determine if these pigmentary changes are permanent or transient, and if visual acuity will improve on longer follow-up.

At present, the optimal management of macular hemorrhage from retinal artery macroaneurysms remains unclear, in part because of the difficulty in determining the exact tissue level of the hemorrhage at the fovea. The current study indicated that good visual acuity can be recovered in many patients by means of observational management alone, while avoiding surgery-related morbidity, such as infection and retinal detachment. Macular pigmentary changes after resorption of hemorrhage may result in more limited visual recovery. Since many of these patients have multiple medical problems, observational management can be considered as a reasonable alternative to surgical intervention for some patients.

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Article Information

Accepted for publication January 9, 2000.

Maria Berrocal, MD, San Juan, Puerto Rico; Mark Blumenkranz, MD, Palo Alto, Calif; David Chow, MD, Royal Oak, Mich; M. Gilbert Grand, MD, St Louis, Mo; Robert Haimovici, MD, Boston, Mass; Robert Johnson, MD, San Francisco, Calif; Shalesch Kaushal, MD, St Louis; Hilel Lewis, MD, Cleveland, Ohio; Richard Lewis, MD, Houston, Tex; David Quillen, MD, Hershey, Pa; George Sanborn, MD, Richmond, Va; Steven Sanislo, MD, Cleveland; and Scott Sneed, MD, Phoenix, Ariz.

Corresponding author: Harry W. Flynn, Jr, MD, Bascom Palmer Eye Institute, 900 NW 17th St, Miami, FL 33136 (e-mail: hflynn@med.miami.edu).

References
1.
Robertson  DM Macroaneurysms of the retinal arteries. Trans Am Acad Ophthalmol Otolaryngol. 1973;77OP55- OP67
2.
Rabb  MFGagliano  DATeske  MP Retinal arterial macroaneurysms. Surv Ophthalmol. 1988;3373- 96Article
3.
Panton  RWGoldberg  MFFarber  MD Retinal artery macroaneurysms: risk factors and natural history. Br J Ophthalmol. 1990;74595- 600Article
4.
Brown  DMSobol  WMFolk  JCWeingeist  TA Retinal arteriolar macroaneurysms: long term visual outcome. Br J Ophthalmol. 1994;78534- 538Article
5.
Glatt  HMachemer  R Experimental subretinal hemorrhage in rabbits. Am J Ophthalmol. 1982;94762- 773Article
6.
Toth  CAMorse  LSHjelmeland  LMLanders  MB  III Fibrin directs early retinal damage after experimental subretinal hemorrhage. Arch Ophthalmol. 1991;109723- 729Article
7.
Brent  BDGonce  MDiamond  JG Pars plana vitrectomy for complications of retinal arterial macroaneurysms: a case series. Ophthalmic Surg. 1993;24534- 536
8.
Lewis  H Intraoperative fibrinolysis of submacular hemorrhage with tissue plasminogen activator and surgical drainage. Am J Ophthalmol. 1994;118559- 568
9.
Ibanez  HEWilliams  DFThomas  MA  et al.  Surgical management of submacular hemorrhage: a series of 47 consecutive cases. Arch Ophthalmol. 1995;11362- 69Article
10.
Terasaki  HMiyake  YKondo  MTanikawa  A Focal macular electroretinogram before and after drainage of macular subretinal hemorrhage. Am J Ophthalmol. 1997;123207- 211
11.
Saika  SYamanaka  AYamanaka  A  et al.  Subretinal administration of tissue-type plasminogen activator to speed the drainage of subretinal hemorrhage. Graefes Arch Clin Exp Ophthalmol. 1998;236196- 201Article
12.
Kamei  MTano  YMaeno  TIkuno  YMitsuda  HYuasa  T Surgical removal of submacular hemorrhage using tissue plasminogen activator and perfluorocarbon liquid. Am J Ophthalmol. 1996;121267- 275
13.
Lim  JIDrews-Botsch  CSternberg  P  JrCapone  A  JrAaberg Sr  TM Submacular hemorrhage removal. Ophthalmology. 1995;1021393- 1399Article
14.
Wade  ECFlynn  HW  JrOlsen  KRBlumenkranz  MSNicholson  DH Subretinal hemorrhage management by pars plana vitrectomy and internal drainage. Arch Ophthalmol. 1990;108973- 978Article
15.
Homayun  MLewis  HFlynn  HW  JrSternberg  P  JrBlumenkranz  MS Management of submacular hemorrhage associated with retinal artery macroaneurysms. Am J Ophthalmol. 1998;126358- 361Article
16.
Hochman  MASeery  CMZarbin  MA Pathophysiology and management of subretinal hemorrhage. Surv Ophthalmol. 1997;42195- 213Article
17.
Hayasaka  SUchida  MSetogawa  T Subretinal hemorrhages with or without choroidal neovascularization in the maculas of patients with pathologic myopia. Graefes Arch Clin Exp Ophthalmol. 1990;228277- 280Article
18.
Berrocal  MHLewis  MLFlynn  HW  Jr Variations in the clinical course of submacular hemorrhage. Am J Ophthalmol. 1996;122486- 493
19.
Bennett  SRFolk  JCBlodi  CFKlugman  M Factors prognostic of visual outcome in patients with subretinal hemorrhage. Am J Ophthalmol. 1990;10933- 37
20.
Avery  RLFekrat  SHawkins  BSBressler  NM Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina. 1996;16183- 189Article
21.
Zhao  PHayashi  HOshima  KNakagawa  NOhsato  M Vitrectomy for macular hemorrhage associated with retinal artery macroaneurysm. Ophthalmology. 2000;107613- 617Article
22.
Iijima  HSatoh  STsukahara  S Nd:YAG laser photodisruption for preretinal hemorrhage due to retinal macroaneurysm. Retina. 1998;18430- 434Article
23.
Ohji  MSaito  YHayashi  ALewis  JMTano  Y Pneumatic displacement of subretinal hemorrhage without tissue plasminogen activator. Arch Ophthalmol. 1998;1161326- 1332Article
24.
Hassan  ASJohnson  MWSchneiderman  TE  et al.  Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology. 1999;1061900- 1907Article
25.
Heriot  WJ Intravitreal gas and TPA: an outpatient procedure for submacular hemorrhage.  Paper presented at: Vitreoretinal Frontiers October 25, 1996 Chicago, Ill
26.
Johnson  MWOlsen  KRHernandez  EIrvine  WDJohnson  RN Retinal toxicity of recombinant tissue plasminogen activator in the rabbit. Arch Ophthalmol. 1990;108259- 263Article
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