Management of Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration With Anti–Vascular Endothelial Growth Factor Monotherapy

doi:10.1016/j.ajo.2013.01.012

American Journal of Ophthalmology

Volume 155, Issue 6, June 2013, Pages 1009-1013

https://doi.org/10.1016/j.ajo.2013.01.012 Get rights and content

Purpose

To report the visual and anatomic outcomes of anti–vascular endothelial growth factor (VEGF) monotherapy in the management of marked submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD).

Design

Retrospective, interventional, consecutive case series.

Methods

Nineteen eyes of 18 patients with neovascular AMD and fovea involving submacular hemorrhage comprising greater than 50% of the lesion area were treated with anti-VEGF monotherapy. Main outcome measures included mean visual acuity change from baseline, mean central lesion thickness change from baseline, mean number of injections at 6 months, and adverse events. Snellen visual acuity was converted to approximate ETDRS letter score for the purpose of statistical analysis.

Results

The mean change in approximate ETDRS letter score from baseline was +12 letters at 3 months (P = .003), +18 letters at 6 months (P = .001), and +17 letters at 12 months follow-up (P = .02). Seven eyes received ranibizumab, 6 eyes received bevacizumab, and 6 eyes received both at various time points. The mean number of injections at 6 months was 4.7. The mean OCT central lesion thickness decreased from 755 μm to 349 μm at 6 months follow-up (P = .0008).

Conclusions

Management with anti-VEGF monotherapy may yield visual and anatomic improvements in eyes with marked submacular hemorrhage secondary to neovascular AMD.

Section snippets

Methods

Institutional review board approval from the University of Miami Miller School of Medicine was obtained to review patient data for this retrospective, interventional, consecutive case series from 3 treating physicians (H.W.F., W.E.S., P.J.R.) at Bascom Palmer Eye Institute. Informed consent was not required for this de-identified review.

Medical records were reviewed for all patients presenting between 2008 and 2011 with a diagnosis of neovascular AMD and fovea involving submacular hemorrhage

Results

Nineteen eyes of 18 patients met the inclusion and exclusion criteria. The mean age was 81 years. Seven eyes received ranibizumab, 6 eyes received bevacizumab, and 6 eyes received both. The range to last follow-up examination was 4-30 months. The mean number of injections over the first 6 months was 4.7 (range 2-7, n = 15). The mean baseline area of submacular hemorrhage was 39.0 mm² (range 4.3-170.2 mm², n = 16).

Eighteen of 19 eyes (95%) were evaluated at the 3-month follow-up interval. Median

Discussion

This study has demonstrated an improvement in visual acuity after nonsurgical, monotherapy treatment with intravitreal anti-VEGF injections. Previous natural history studies have shown that untreated patients with submacular hemorrhage secondary to neovascular AMD lose, on average, 3 or more lines of vision at 3 years of follow-up.11, 22 Submacular surgery increases the risk of cataract progression, vitreous hemorrhage, retinal detachment, and proliferative vitreoretinopathy while offering

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Cited by (70)

Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration
2023, Ophthalmology
To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm.
Randomized, open-label, multicenter superiority study.
Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium.
Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 μg], and 20% sulfur hexafluoride [SF₆] tamponade) or PD (0.05 ml intravitreal tPA [50 μg] and 0.3 ml intravitreal pure SF₆). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up.
The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up.
Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7–24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1–25.7 letters]; adjusted difference β, 1.9 [–11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group.
Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Role of intravitreal brolucizumab with intravitreal rtPA and pneumatic displacement for submacular hemorrhage: A case series
2022, American Journal of Ophthalmology Case Reports
Citation Excerpt :
These include a combination of modalities such as intravitreal gas injection, intravitreal or subretinal recombinant tissue plasminogen activator (rtPA), anti-VEGF injection, and pars plana vitrectomy (PPV).6 Amongst the various anti-VEGF agents currently available, bevacizumab (AVASTIN, Genentech, Inc.,), ranibizumab (Lucentis®; Genentech, S. San Francisco, CA/Roche, Basel, Switzerland), and aflibercept (Eylea®, Regeneron, Tarrytown, NY) have been successfully employed for the management of SMH.7,8 Brolucizumab (Beovu®; Novartis, Basel, Switzerland), the most recent anti-VEGF agent, received the US Food and Drug Administration (FDA) approval for nAMD in 2019.9
To evaluate the role of intravitreal injection (IVI) of brolucizumab along with intravitreal recombinant tissue plasminogen activator (rtPA) and C3F8 gas injection for large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD).
This was a prospective uncontrolled non-randomized case series conducted at a single site. Three patients with fresh SMH (≤4 days) secondary to nAMD underwent triple therapy with IVI brolucizumab + intravitreal rtPA (50 μg in 0.1 mL) + 0.3 mL of 100% C3F8 gas injection. Post-injection, a face-down position was advised for 5 days with periodic follow-up visits. All three patients had complete resolution of SMH at the end of 4 weeks with a notable improvement in the best-corrected visual acuity (BCVA). No optical coherence tomographic (OCT) biomarkers of disease activity were noted at the end of 12 weeks in the first and the third case and 4 weeks in the second case respectively. There were no ocular or systemic side effects reported in any of the cases.
Intravitreal brolucizumab administered along with intravitreal rtPA and C3F8 gas injection was found to be efficacious and safe for the management of large SMH secondary to nAMD. Complete displacement of SMH with excellent structural and functional outcomes can be seen with triple therapy.
Human Amniotic Membrane Plug to Restore Age-Related Macular Degeneration Photoreceptor Damage
2020, Ophthalmology Retina
Citation Excerpt :
Differently from our study, they enrolled only patients with no history of intravitreal anti-VEGF injections who were affected by a flat, large subretinal hemorrhage with a mean central macular thickness of less than 340 μm and no subretinal scar or fibrovascular tissue present. Shienbaum et al,72 in 2013, treated 19 patients using anti-VEGF injections for CNV complicated by large submacular hemorrhage. The patients enrolled in that study showed elevated central macular thickness but no subretinal scar of fibrosis tissue.
Age-related macular degeneration (AMD) is the leading cause of legal blindness in adults 65 years of age and older. Choroidal neovascularization (CNV) can complicate AMD and lead to severe visual acuity reduction. Despite the several treatments available, if the retinal pigment epithelium is damaged, we have to cope with the impossibility of restoring acceptable visual acuity using only medical treatments.
Prospective, consecutive, interventional study.
Eleven patients affected by AMD, 6 patients affected by CNV, and 5 patients affected by geographic atrophy.
All patients underwent a pars plana vitrectomy with subretinal implantation of human amniotic membrane (hAM) to induce photoreceptor regeneration and partial visual acuity restoration.
Primary study outcome was visual acuity improvement. Secondary outcomes were multimodal imaging results.
Mean preoperative best-corrected visual acuity (BCVA) was 20/2000 (2 logarithm of the minimum angle of resolution [logMAR]), and all the patients showed a BCVA of counting fingers or less. Mean final BCVA was 20/400 (1.31 logMAR), ranging from 20/2000 to 20/100 (2–0.7 logMAR). OCT angiography was used to measure retinal vascularization in the treated eye compared with the fellow eye. A high correlation between BCVA and deep vascular density was evidenced. Adaptive optics findings, obtained over the retinal area where the highest functionality was observed, were evaluated using microperimetry. The images showed possible photoreceptor presence over the hAM membrane.
This work supports the feasibility and safety of the hAM to promote partial retinal function restoration 6 months after surgery with visual acuity improvement. The advanced diagnostics help to understand the interaction between the hAM and photoreceptors and suggest that photoreceptor regeneration may occur.
Young Woman With Unilateral Vision Loss
2019, Annals of Emergency Medicine
Outcomes in the Treatment of Subretinal Macular Hemorrhage Secondary to Age-Related Macular Degeneration: A Systematic Review
2024, Journal of Clinical Medicine
Current Management of Subretinal Hemorrhage in Neovascular Age-Related Macular Degeneration
2023, Ophthalmologica

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Original articleManagement of Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration With Anti–Vascular Endothelial Growth Factor Monotherapy

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Fibrin directs early retinal damage after experimental subretinal hemorrhage

Arch Ophthalmol

Subretinal hemorrhage management by pars plana vitrectomy and internal drainage

Arch Ophthalmol

Surgical removal of subretinal hemorrhage and choroidal neovascular membranes in acute hemorrhagic age-related macular degeneration

Can J Ophthalmol

Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement

Ophthalmology

Tissue plasminogen activator plus gas injection in patients with subretinal hemorrhage caused by age-related macular degeneration: predictive variables for visual outcome

Graefes Arch Clin Exp Ophthalmol

Original article
Management of Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration With Anti–Vascular Endothelial Growth Factor Monotherapy