Macular Hole Formation Following Vitrectomy with Subretinal tPA Injection for Massive Subretinal Hemorrhage: A Case Report

doi:10.21203/rs.3.rs-4811447/v1

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Case Report

Macular Hole Formation Following Vitrectomy with Subretinal tPA Injection for Massive Subretinal Hemorrhage: A Case Report

https://doi.org/10.21203/rs.3.rs-4811447/v1

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Background: Subretinal hemorrhages, particularly massive ones, are commonly observed in wet age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Subretinal injection of tissue plasminogen activator (tPA) can assist in clot liquefaction and facilitate hemorrhage displacement. However, this procedure has occasionally been associated with complications such as retinal detachment, recurrent subretinal hemorrhage, and macular hole formation. Herein, we present a full-thickness macular hole developed with subretinal tPA injection for massive subretinal hemorrhage in PCV.

Case presentation：

A 60-year-old female with a decade-long history of diabetes mellitus reported a sudden decrease in visual acuity in her right eye over the past month. The best-corrected visual acuity (BCVA) at presentation was HM/10cm due to dense vitreous hemorrhage, which precluded a funduscopic examination. Preoperative B-scan ultrasonography revealed vitreous echo-density consistent with vitreous hemorrhage and an echo dense dome-shaped subretinal hemorrhage throughout the quadrant. The patient underwent combined phacoemulsification and vitrectomy with subretinal injection of tPA and pneumatic displacement of the subretinal hemorrhage. On the first postoperative day, her visual acuity decreased to light perception, intraocular pressure (IOP) rose to 40 mmHg, and the anterior chamber was filled with hemorrhage. B-scan ultrasound indicated a massive vitreous hemorrhage with shallow retinal detachment, and the subretinal hemorrhage appeared displaced entirely. Given the high IOP and extensive vitreous hemorrhage, immediate additional vitrectomy with silicone oil tamponade was performed. Subsequently, a small macular hole developed, with hemorrhage entering the vitreous cavity through the hole. Four months of follow-up showed complete closure of the macular hole.

Conclusions: Macular hole formation can occur following subretinal tPA injection. While the exact mechanism remains unclear, additional vitrectomy achieves macular hole closure.

subretinal injection

macular hole

subretinal hemorrhage

polypoidal choroidal vasculopathy

tissue plasminogen activator

Subretinal injection of tPA is a widely used treatment for subretinal hemorrhage caused by conditions such as wet AMD, polypoid choroidal vasculopathy, and retinal aneurysms [1, 2]. However, potential complications, including retinal detachment, vitreous hemorrhage, recurrent subretinal hemorrhage, and macular hole formation, should not be overlooked [3]. We report a unique case of macular hole formation after subretinal tPA injection, which healed spontaneously after silicone oil tamponade without internal limiting membrane peeling. To our knowledge, this is the first report of a full-thickness macular hole developing concurrently retinal detachment in the setting of massive hemorrhage from PCV.

The patient, a 60-year-old female, presented on January 1, 2024, with a sudden decrease in visual acuity in the right eye over the past month. She had a history of diabetes mellitus for ten years and a hemoglobin A1C of 9.4%. Ophthalmic examination revealed a BCVA of hand motion in the right eye and 0.8 in the left eye. The intraocular pressure (IOP) was 18 mmHg in both eyes. Moderate lens opacification was noted in the anterior segment examination. Dense vitreous hemorrhage obscured the fundus in the right eye. Preoperative B-scan ultrasonography showed vitreous echo density consistent with vitreous hemorrhage and an echo-dense dome-shaped subretinal hemorrhage in the whole quadrant (Fig. 1A). The patient consented to combined phacoemulsification and vitrectomy with subretinal injection of tPA and pneumatic displacement of the subretinal hemorrhage. The posterior hyaloid face was closely adhered to the retina, complicating posterior vitreous detachment (Fig. 1B). After elevating and clearing the posterior hyaloid, massive subretinal hemorrhage and diffuse retinal detachment were noted, with no hole detected. Perfluorocarbon liquid was instilled to displace the sub-macular hemorrhage peripherally, facilitating tPA injection in each quadrant(total 0.08ml, 20µg /0.1 mL). After complete air-fluid exchange, the patient was positioned face-down postoperatively to displace the sub-macular hemorrhage.

On the first postoperative day, the visual acuity in the right eye decreased to light perception, and the IOP was high at 40 mmHg. The anterior chamber was full of hemorrhage. B-scan ultrasound indicated a massive vitreous hemorrhage with shallow retinal detachment, and the subretinal hemorrhage seemed completely displaced (Fig. 2). Considering the high IOP and massive vitreous hemorrhage, immediate additional vitrectomy was performed, during which a small macular hole (approximately 500 microns in diameter) was detected, associated with diffuse retinal detachment. The hemorrhage was seen entering the vitreous cavity through the macular hole (Fig. 3). The internal limiting membrane (ILM) was not peeled due to the blurry visual field caused by corneal edema. Given the concurrent macular hole and retinal detachment, silicone oil tamponade was performed after a complete air-fluid exchange.

Close follow-up was conducted in the outpatient clinic. After two weeks, visual acuity in the right eye remained at hand motion, with IOP measuring 25 mmHg. The subretinal hemorrhage had resolved mainly, and optical coherence tomography (OCT) revealed a macular hole filled with hyper-reflective material (Fig. 4).

Four months later, the BCVA in the right eye had improved to count fingers, and IOP was 17 mmHg. Fundus photography showed subretinal yellowish-white material deposits in the macular area and an orange-red subretinal nodule superior to the arcade (Fig. 5A). OCT indicated complete macular hole closure but with a disordered external limiting membrane structure and ellipsoid zone structure. Additionally, hyper-reflective material was noted between the retinal pigment epithelium and Bruch's membrane, indicative of a branching vascular network and a peaked pigment epithelial detachment corresponding to the polyp (Fig. 5B). On OCT angiography (OCTA) examination. En-face angiogram of the outer retina segmentation shows a hyper-reflective neovascular network suggestive of the branching vascular network (BVN), with a hypo-reflective roundish region at the terminal ends corresponding to a hypo-reflective polyp (white arrow) (Fig. 5C).

Subretinal hemorrhage (SRH), the accumulation of blood between the neurosensory retina and the retinal pigment epithelium (RPE) or between the RPE and the choroid, can cause rapid tissue damage accompanied by photoreceptor and RPE degradation, resulting in poor visual outcomes, mainly if the hemorrhage occurs in the macular area[4, 5]. Subretinal injection of tPA may help liquefy the clot and aid in hemorrhage displacement with the assistance of vitrectomy and gas tamponade [1]. However, macular hole development following such injections has been reported, with 4–12% occurrence rates in wet AMD and PCV [3, 6].

The development of a macular hole may potentially be attributed to the force of infusion during subretinal tPA injection, which could separate the fovea due to solid adhesion to the subretinal clot, especially if the injection site is near the fovea[6, 7]. However, with the assistance of Perfluorocarbon Liquids (PFCL), the injection point of our case was distant from the macular, akin to the technique described by Steel. The PFCL forces the injected subretinal fluid to spread laterally, resulting in a lower bleb with less tendency to distend vertically into a convex dome. It reduces tensile stress at the fovea as it detaches[8].

Another potential mechanism for macular hole occurrence is tangential retinal stretching. It is hypothesized that tangential and anteroposterior forces arise from vitreous hemorrhage, inducing traction from a contracted posterior vitreous cortex [9, 10]. In our case, the posterior hyaloid face was closely adhered to the retinal, complicating artificial posterior vitreous detachment, which might induce tangential and anteroposterior forces contributing to MH formation. However, after artificial posterior vitreous detachment, we did not find a macular hole or subretinal hemorrhage escape from the macular area.

In our case, the possible cause of macular hole formation could be attributed to the extended duration from symptom onset to surgery. Research suggests a long disease duration or thin fovea may be risk factors for macular hole development [3]. It is hypothesized that eyes with AMD may exhibit atrophic and degenerative changes predisposing to foveal dehiscence [11].

Following MH formation, most cases typically require additional vitrectomy with techniques like inverted ILM flap and expansile gas tamponade, which have shown closure success. However, in our case, the MH closed without ILM peeling four months later after silicone oil tamponade. Hyper-reflective material in MH, shown in the OCT image, was identified as likely blood remnants. Blood components have been used to facilitate hole closure by potentially enhancing the healing process through platelets and various growth factors promoting tissue regeneration[12].

In conclusion, our case demonstrates that a macular hole would develop after Subretinal tPA injection for PCV and massive subretinal hemorrhage. However, the precise mechanism of this complication was unknown, and prolonged symptom onset to surgery may be a contributing risk factor for MH. Therefore, prompt vitrectomy combined with subretinal tPA injection should be considered. When MH occurs, additional vitrectomy can achieve favorable anatomical outcomes.

Funding

No funding was received by any of the authors in the writing of this manuscript.

Availability of data and materials

All data supporting our findings are provided in the manuscript.

Authors’ contributions

DGH drafted the manuscript, participated in the acquisition, analysis and interpretation of data and reviewed the literature.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Written informed consents were obtained for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this journal.

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki and approved by ethics committee board of the Joint International Eye Center. The patients was provided a written informed consent for their participation in the study and for the surgical procedure.

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Tao, J., et al., Inverted Internal Limiting Membrane Flap Coverage With Autologous Blood Technique After Air-Fluid Exchange and Silicone Oil Tamponade for Extensive Macular Hole Retinal Detachment in Highly Myopic Eyes. Retina, 2024. 44(7):1268-1273.

No competing interests reported.

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Macular Hole Formation Following Vitrectomy with Subretinal tPA Injection for Massive Subretinal Hemorrhage: A Case Report

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