Simultaneous Bevacizumab, Tissue Plasminogen Activator Effective for Submacular Hemorrhage

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New research suggests the administration of subretinal bevacizumab, and subretinal tissue plasminogen activator (tPA), effectively removes submacular hemorrhage under the fovea, a potentially devastating complication of neovascular age-related macular degeneration (nAMD).¹

As choroidal neovascular membrane (CNVM) activity is known to continue post-surgery, the investigative team from Eye Clinic Istanbul noted intravitreal anti-vascular endothelial growth factor (VEGF) treatment is required to sustain the period of best-corrected visual acuity (BCVA) improvement.

“Our favorable results indicate that mean BCVA improvement and CFT decrease were statistically significant at all follow-up visits,” wrote the investigative team, led by Utku Limon, MD. “At the same time, we have shown that repeated injections are required to maintain the increase in visual acuity.”

Submacular hemorrhages are an accumulation of blood between the neurosensory retina and retinal pigment epithelium and are an important cause of sudden visual loss. A large and thick submacular hemorrhage related to CNVM in nAMD can lead to a poor visual prognosis if left untreated or if patients are significantly delayed in receiving treatment. Given its poor prognosis, various treatments, including anti-VEGF injection, intravitreal or subretinal tPA injection, or surgical removal, have been explored in prior literature.²

In this analysis, Limon and colleagues evaluated patients who underwent pars plana vitrectomy (PPV) with simultaneous tPA with 18% SF6 tamponade and subretinal bevacizumab for SMH secondary to nAMD.¹ The team reviewed the medical records of all cases occurring from 2016 to 2022. Inclusion criteria included patients treated within 10 days of onset of symptoms and patients with ≥1 year of the follow-up period.

Investigators used the caliper function of optical coherence tomography (OCT) to measure the maximal SMH height and central foveal thickness (CFT). The maximum height of SMH was defined as the maximum distance between the upper surface of the SMH and the inner surface of the RPE. Patients were retreated with pro re nata anti-VEGF protocol with monthly visits.

The analysis’ primary outcome was changes in BCVA and anatomical improvement from baseline over the follow-up period. Investigators analyzed the medical records of 11 cases of SMH secondary to nAMD. Patients had a mean age of 72.4 years, and the mean time from the onset of symptoms to treatment was 5.13 days.

Patients had a mean BCVA was 2.23 ± 0.14 logMAR at baseline. Upon analysis, the mean BCVA increased significantly in the 1st, 6th, and 12th months to 1.68 ± 0.47 logMAR, 1.58 ± 0.49 logMAR, and 1.51 ± 0.58 logMAR, respectively (P = .001 for all). At month 12, all patients’ BCVA was better than baseline.

Regarding anatomical outcomes, the mean maximum measurable SMH height in five patients at baseline was 814.2 ± 556.45 µm. The mean CFT in measurable patients was 836.8 ± 627.02 µm at baseline.

In the analysis, investigators found the mean CFT significantly decreased to 370.13 ± 66.13 µm in the 1st month, 373.38 ± 78.33 µm in the 6th month, and 367.75 ± 116.43 µm in the 12th month (P <.05).

A total of 7 patients (87.55) required additional intravitreal bevacizumab treatment during the follow-up period. These patients received a mean of 4.13 ± 2.1 additional intravitreal bevacizumab injections. At month 12, investigators could not detect the ellipsoid zone in 6 patients.

Limon and colleagues indicate the single-center, retrospective design, small number of patients, and the lack of a control group limit these findings, suggesting further studies are necessary to clarify these reported effects.

“Future prospective studies with a greater number of patients are needed to help clarify the efficacy of subretinal anti-VEGF therapies and tPA for the treatment of CNVM-associated SMH.

References

1. Limon U, Gezginaslan TA, Saygin IO, Bozkurt E, Kardes E, Akcay BIS. Efficacy of Simultaneous Application of Subretinal Tissue Plasminogen Activator and Bevacizumab for Submacular Hemorrhages. Beyoglu Eye J. 2023;8(3):198-207. Published 2023 Sep 13. doi:10.14744/bej.2023.34735
2. Sniatecki J, Ho-Yen G, Clarke B, Barbara R, Lash S, Papathomas T, et al. Treatment of submacular hemorrhage with tissue plasminogen activator and pneumatic displacement in age-related macular degeneration. Eur J Ophthalmol. 2021;31:643–8