Surgical management of two cases with macular exudation from retinal macroaneurysms refractory to focal photocoagulation

Abstract

Purpose

To report two cases of macular exudations resulting from retinal arterial macroaneurysms (MaAs) refractory to focal photocoagulations that were treated with a new surgical technique including subretinal balanced saline solution (BSS) injection to dilute lipid-rich subretinal fluid (SRF) and facilitate absorption of the SRF, intentional retinal hole formation to direct SRF into the vitreous cavity, and laser photocoagulation posterior to the MaAs to prevent intraretinal fluid and SRF from reaching the fovea.

Observations

A 70-year-old man with macular edema (ME) refractory to anti-vascular endothelial growth factor (VEGF) therapy was referred to our hospital. Fundus examination showed retinal arterial MaAs and hard exudations. He underwent laser photocoagulation, sub-Tenon injections of triamcinolone acetonide (STTA), and anti-VEGF therapies; the ME recured despite all treatments. Subretinal lipid-rich exudatoins from retinal arterial MaAs involved the macula, which led to severe vision loss. Therefore, vitrectomy with the new technique was planned to flush out the lipid-rich SRF and prevent new exudations from reaching the macula. Postoperatively, the SRF resolved completely and the ME has not reccured until 59 months postoperatively at his latest visit. The second patient was a 77-year-old woman with an epiretinal membrane and ME with sarcoidosis. She underwent anti-VEGF therapy, STTA injection, and focal laser photocoagulation. The vision-threatening ME persisted. She underwent vitrectomy with the new technique, and the macular exudation resolved promptly. The ME has not recurred 27 months postoperatively.

Conclusions

Vitrectomy with this technique may be considered in cases with vision-threatening ME due to retinal MaAs resistant to combined multiple conventional treatments.

1. Introduction

Retinal arterial macroaneurysms (MaAs) are usually described as an idiopathic, acquired focal aneurysmal dilatation of arterioles, typically associated with systemic hypertension and arteriosclerotic vascular changes accompanied by cardiovascular diseases.^1,2 MaAs or telangiectatic capillaries accompany a variety of retinal vascular diseases including Coats' disease, Leber's miliary aneurysms, von Hippel-Lindau syndrome (familial arterial MaAs), diabetic retinopathy, retinal vein occlusion, ectopic neovascular membrane, radiation retinopathy, idiopathic retinal vasculitis, arteriolar MaAs and neuroretinitis and other types of uveitis, and malignant melanoma.1, 2, 3, 4 The patient usually is asymptomatic unless there is macular edema (ME) due to exudation from a MaA, hemorrhage caused by a ruptured aneurysm, or end-arteriole occlusion due to thrombosis.⁵

Most MaAs resolve and regress spontaneously, requiring no therapeutic intervention. However, the hemorrhagic or exudative form of MaAs, especially when the macula is involved, sometimes requires a variety of treatments. Treatment modalities in eyes with hemorrhages include yttrium aluminum garnet laser hyaloidotomy for sub-internal limiting membrane (ILM) hemorrhage, pneumatic displacement of submacular hemorrhage, and vitrectomy for vitreous hemorrhage, sub-ILM and submacular hemorrhages.6, 7, 8 Although there are no standard guidelines for the treatment of ME due to the exudative form of MaA, direct and indirect focal laser photocoagulation, intravitreal anti-vascular endothelial growth factor (VEGF) injections, or a combination of both are the current treatment options.8, 9, 10, 11 However, repeated focal laser photocoagulation at higher energy levels carries a significant risk of complications, such as branch retinal artery occlusion. While anti-VEGF therapy showed clinical benefits, this indication for anti-VEGF therapy remains unapproved in our country. Furthermore, not all cases respond to these treatments. Therefore, alternative treatment strategies should be considered for these refractory cases.

We present 2 cases treated with a new surgical procedure to treat persistent ME secondary to retinal arterial MaAs despite focal laser photocoagulation, anti-VEGF therapy, or both.

2. Case reports

A 70-year-old man presented to our hospital for ME in his right eye that was refractory to anti-VEGF therapy. He had already received two intravitreal injections of aflibercept (Eylea, Regeneron Pharmaceuticals, Tarrytown, NY). At the initial visit, the best-corrected visual acuities (BCVAs) expressed in decimal notation in the right and left eyes, respectively, were 0.7 and 1.2. Funduscopy showed retinal arterial MaAs and surrounding hard exudates (Fig. 1). Optical coherence tomography (OCT) showed ME extending to the macula. Fluorescein angiography confirmed the diagnosis of Leber's miliary aneurysms. During the 4-year follow-up period, he underwent laser photocoagulation to the MaAs, 6 sub-Tenon injections of triamcinolone acetonide (STTA), and 2 intravitreal injections of ranibizumab (Lucentis, Genentech, South San Francisco, CA). Despite the treatments, MaAs tended to recur, persist, and newly develop.

Fig. 1.

Fundus and OCT images of case 1. Upper rows: Fundus images overlaying an OCT map. Middle and lower rows: OCT images. (A) Images obtained at the first visit show a fundus image overlaying an OCT map; retinal edema and hard exudates are seen in the superonasal quadrant (upper row). (B) Images obtained preoperatively show a fundus image overlaying an OCT map; ME is seen. The arrowhead indicates the MaA (upper row). OCT shows intraretinal and subretinal exudates (middle and lower rows). (C) Fundus and OCT images obtained 1 month postoperatively show complete resolution of the subfoveal exudates and that the intentionally created hole remains open and functioning as a moat. (D) Images obtained 3 months postoperatively show photocoagulation spots functioning as a wall surrounded by yellow dots. (E) OCT images obtained 6 months postoperatively show that the intentionally created retinal hole functioning as a moat has closed (lower row, arrowhead). (F) Images obtained 12 months postoperatively show that the subfoveal fluid never recurred up to 12 months postoperatively.

One year after the sixth laser photocoagulation, a subretinal lipid-rich exudation from a MaA superior to the macula involved the macula, resulting in severe vision loss. The BCVA in his right eye decreased to 0.04. This MaA was refractory to laser photocoagulation. Therefore, vitrectomy with the new technique, referred to as the “moat-and-wall technique,” was planned to flush out the lipid-rich subretinal fluid (SRF) that threatens vision and prevent new exudates from reaching the macula. The patients underwent 25-gauge vitrectomy (Constellation®, Alcon Japan, Ltd., Tokyo, Japan). The cutting rate and aspiration pressure were set to be 10,000 cuts/min and 650 mmHg. After a core vitrectomy, the ILM was peeled toward the fovea but not over the fovea to avoid macular hole formation during the subsequent subretinal injection. The ILM of the retina posterior to the MaA and the ILM over the MaA also were removed. Balanced salt solution (BSS) was injected into the subretinal space with a 38-gauge needle (Extendable PolyTip® Cannula 25g/38g, MedOne Surgical, Inc., Sarasota, FL) to wash out the lipid-rich SRF. Diathermy was applied to the retina posterior to the MaA to create an intentional retinal hole to serve as a moat. Diathermy was performed on the MaA itself. Subsequently, ILM peeling was completed over the fovea to avoid postoperative serum-derived epiretinal membrane (ERM) formation. A fluid-air exchange was performed followed by laser photocoagulation posterior to the intentional hole to induce formation of a disorganized retinal inner layer (DRIL) and adhesion of the outer retina to the retinal pigment epithelium layer that could block exudate infiltration into the macula as if to build a castle wall. The patient required prone posturing overnight.

Immediately postoperatively, the SRF completely resolved. One month later, the subfoveal exudate disappeared and the intentional hole remained open and appeared to be functioning as a moat. The BCVA improved to 0.3. Three months later, the MaA remained active, but the ME had not recurred. The intentional hole serving as a moat closed spontaneously 6 months postoperatively. Thereafter, this MaA spontaneously regressed and reactivated with no recurrent ME, and the BCVA remained stable. The DRIL formation and retinal adhesion to the retinal pigment epithelium layer, intentionally constructed by laser photocoagulation, appeared to function as a wall. At the last visit 59 months postoperatively, the BCVA was 0.3.

The second case was that of a 77-year-old woman with an ERM and ME with sarcoidosis who was referred to our hospital. She has already received 4 intravitreal injections of aflibercept and 1 STTA in her right eye. At the initial visit, the BCVAs were 0.8 in her right eye and 1.0 in her left eye. Funduscopy and OCT showed an ERM and no ME in her right eye (Fig. 2). During 3 years of follow-up, ME occurred due to uveitis, and a STTA injection was administered twice. A new MaA then developed at an inferotemporal lesion, and the BCVA worsened to 0.2 due to the ME and subfoveal exudation. Focal laser photocoagulation was applied to the MaA and a STTA injection was administered, but the ME and SRF persisted.

Fig. 2.

Fundus and OCT images of case 2. Upper rows: Fundus images overlaying an OCT map. Middle and lower rows: OCT images. (A) OCT images at the first visit show an ERM. (B) Images obtained preoperatively show a fundus image overlaying an OCT map; ME and hard exudates are seen. The arrowhead indicates the MaA (upper row). OCT shows intraretinal and subretinal exudates (middle and lower rows). (C) Fundus and OCT images obtained 1 month postoperatively show that the intraretinal exudates remain but the subfoveal exudates resolved. (D) Images obtained 3 months postoperatively show that the intraretinal exudation has decreased. The photocoagulation shows functioning as a wall is surrounded by yellow dots. (E) Images obtained 6 months postoperatively. (F) Images obtained 12 months postoperatively shows that the intraretinal exudates have resolved and the subfoveal fluid never recurred up to 12 months postoperatively.

She underwent vitrectomy with the moat-and-wall technique. The macular exudation resolved promptly. In month 12, the BCVA improved to 0.5. At the last visit 27 months postoperatively, the ME had not recurred and the BCVA was 0.4.

3. Discussion

Treatment of ME secondary to MaAs depends on the VA, and the location and type of MaAs. When the MaA is below the macula or nasal to the disc with minimal exudation or hemorrhage without vision loss, observation usually is recommended because spontaneous regression and resolution of the MaA can be expected. However, patients with a vision-threatening MaA with subfoveal hemorrhage or exudation need to be treated.6, 7, 8, 9, 10, 11

Wang et al. reported a cohort in which non-surgical management of MaAs, i.e., observation, laser photocoagulation, and anti-VEGF therapy, were compared.⁹ In that study, the patients who were stable with good BCVA and central macular thickness (CMT) below 250 μm were primarily observed. Although anti-VEGF therapy is an off-label use, the change in the CMT was significantly better in the anti-VEGF therapy group than in the laser photocoagulation group. This may have been related to the fact that more exudative cases were treated in the laser photocoagulation group than in the anti-VEGF therapy group.⁹ Despite the efficacy of anti-VEGF therapy, evidence regarding its long-term efficacy and regression rate related to recurrence is lacking.

Although there are no standard guidelines for the treatment of the exudative form of MaAs, observation, focal laser photocoagulation, and anti- VEGF therapy are the current treatment options. However, due to the rarity of the disease, reports on refractory cases are limited. There has been a case report of a patient who developed vitreous hemorrhage after receiving laser photocoagulation and bevacizumab treatment, but subsequently responded well to aflibercept therapy.¹² There has also been a case report of MaAs associated with Coats’ disease, in which exudative changes recurred despite multiple sessions of retinal photocoagulation and anti-VEGF therapy. Although steroid treatment was effective, adverse effects such as elevated intraocular pressure were also observed.¹³ In our report, both cases demonstrated refractory to multiple sessions of anti-VEGF therapy, retinal photocoagulation, and steroid treatment, necessitating the consideration of alternative treatment approaches. We devised a new surgical technique, referred to as the moat-and-wall technique. The keys to this new surgical technique are: 1) subretinal injection of BSS to dilute the lipid-rich SRF and facilitate absorption of SRF; 2) intentional retinal hole formation, which directs fluid from the active MaAs into the vitreous cavity (like a moat); and 3) laser photocoagulation posterior to the MaAs, which prevents intraretinal fluid and SRF from reaching the fovea (like a castle wall). After core vitrectomy, the ILM was peeled at three sites: the macula, BSS injection site, and on a MaA. The ILM peeling at the macula was intended to reduce postoperative serum-associated ERM formation. However, there may be a risk of macular hole formation during subretinal injection of BSS. Therefore, the ILM peeling was carried out toward the fovea but did not extend over the fovea and was completed after subretinal injection of BSS (and before intentional retinal hole formation). The ILM peeling at the BSS injection site was performed to enable subretinal injection at pressures as low as 6–10 mmHg using the VFC mode of the Constellation®. The BSS injection site was the same site where the retinal hole was created, i.e., just posterior to the MaA. The ILM peeling on the MaA and the intentional hole formation as a moat were performed to direct fluid into the vitreous cavity. To reduce exudation from the MaA, diathermy of the MaAs was performed. After fluid-air exchange, laser photocoagulation was performed only posterior to the intentional retinal hole to create a wall with a scar across the retina, preventing both intraretinal fluid and SRF from reaching the fovea. Because postoperative vitreous traction was not anticipated, laser photocoagulation was not applied anterior to the intentional retinal hole. In fact, no rhegmatogenous retinal detachment occurred in either eye.

Our study had several limitations. This was a small case report without a control group. The postoperative follow-up period was up to 59 months, which may still be insufficient to evaluate long-term visual prognosis, recurrence rate, and potential complications. Additionally, since MaAs may spontaneously regress, it is difficult to determine whether the observed outcomes were solely attributable to the surgical intervention. However, due to the rarity of the disease, it was difficult to include controls or compare with other treatments.

Although we described only two cases that underwent vitrectomy with this technique, prompt anatomic and functional improvement were obtained with no adverse events in both cases. Thus, vitrectomy with this technique may be considered in cases with vision-threatening ME refractory to multiple combined conventional treatments. The long-term outcomes of this surgical technique should be investigated in more eyes and a comparative randomized study conducted.

CRediT authorship contribution statement

Yuta Usami: Writing – original draft, Investigation. Masayo Kimura: Writing – original draft, Investigation. Atsuki Matsumoto: Investigation. Aoi Kominami: Investigation. Hiroshi Morita: Investigation. Tsutomu Yasukawa: Conceptualization, Writing – review & editing.

Declaration

The procedures used in this study adhered to the tenets of the Declaration of Helsinki. Both patients provided signed informed consent after receiving a thorough explanation of the planned surgical procedures and potential complications.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the authors used ChatGPT in order to translate and improve accuracy. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Funding/financial support

This research was funded by Grant-in-Aid for Young Scientists, Japan Society for the Promotion of Science, grant number 23K15913 (M.K.).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.