Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among individuals aged 65 years and older in the USA. For individuals diagnosed with AMD, approximately 12% experience varying levels of subretinal hemorrhage (SRH), which can be further classified by size into small, medium, and massive measured in disc diameters. SRH is an acute and rare sight-threatening complication characterized by an accumulation of blood under the retina arising from the choroidal or retinal circulation. Released iron toxins, reduced nutrient supply, fibrin meshwork contraction, and outer retinal shear forces created by SRH contribute to visual loss, macular scarring, and photoreceptor damage. SRH treatment strategies aim to displace hemorrhage from the foveal region and prevent further bleeding. Although there are no standardized treatment protocols for SRH, several surgical and nonsurgical therapeutical approaches may be employed. The most common surgical approaches that have been utilized are pars plana vitrectomy (PPV) combined with multiple maneuvers such as the removal of choroidal neovascularization lesions, macular translocation, retinal pigment epithelium patch repair, SRH drainage, intravitreal injection of recombinant-tissue plasminogen activator (tPA), expansile gas and air displacement, and anti-vascular endothelial growth factor (anti-VEGF) injections. Nonsurgical therapeutical approaches include intravitreal anti-VEGF monotherapy, intravitreal tPA administration without PPV, and photodynamic therapy. This review article aims to explore the current treatment strategies and supporting literature regarding both surgical and nonsurgical, of SRH in patients with AMD. Moreover, this article also aims to highlight the distinct treatment modalities corresponding to different sizes of SRH.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among individuals aged 65 years and older in the USA [1‒3]. Approximately 288 million people will suffer from AMD by 2040 worldwide [4]. AMD progresses from early and intermediate stages characterized by drusen, which are constituted by focal extracellular deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane to advanced stages characterized by macular choroidal neovascularization (CNV) or geographic atrophy [1, 4]. 12% of individuals diagnosed with AMD encounter varying degrees of subretinal hemorrhage (SRH) [5‒7]. SRH is an acute and rare sight-threatening complication characterized by an accumulation of blood under the retina arising from the choroidal or retinal circulation [6, 7]. SRH may portend a poor prognosis with most patients experiencing severe vision loss, often worse than 20/200 [8]. There are many factors that affect the prognosis of SRH such as hemorrhage size, location, time to treatment, and potential involvement of other segments. SRH can be classified based on thickness and extension as small, medium, or massive-sized SRH. A small SRH is between ≥1 and <4 disc diameters (DDs), medium-sized is ≥4 DD but confined within the vascular arcades (Fig. 1), and massive-sized is ≥4 DD and extends beyond the temporal arcades (Fig. 2). SRHs that are notably thick (often with a thickness of 400 μm or higher) often result in masking of the RPE during fundus examination and may be associated with worse prognosis (Fig. 3) [9]. Numerous studies have delved into determining the optimal treatment modality tailored to different SRH sizes [9].

Fig. 1.

Medium-sized subretinal hemorrhage is ≥4 DD but confined within the vascular arcades.

Fig. 1.

Medium-sized subretinal hemorrhage is ≥4 DD but confined within the vascular arcades.

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Fig. 2.

Massive subretinal hemorrhage (intraoperative view).

Fig. 2.

Massive subretinal hemorrhage (intraoperative view).

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Fig. 3.

SRHs that are notably thick (often with a thickness of 400 μm or higher) often result in masking of the retinal pigment epithelium (RPE) during fundus examination and may be associated with worse prognosis. Spectral-domain optical coherence tomography image shows a SRH with a thickness of 769 microns.

Fig. 3.

SRHs that are notably thick (often with a thickness of 400 μm or higher) often result in masking of the retinal pigment epithelium (RPE) during fundus examination and may be associated with worse prognosis. Spectral-domain optical coherence tomography image shows a SRH with a thickness of 769 microns.

Close modal

The presence of CNV in AMD is the major risk factor for SRH pathogenesis. Disease pathologies that can lead to SRH without CNV are myopia, trauma, retinal arterial macroaneurysms, and various hematological conditions. Once SRH is present, several local mechanisms lead to visual impairment including iron toxicity, diminished nutrient delivery, contraction of fibrin meshwork, and exertion of shear forces on the outer retinal layer [10]. SRH can also damage the macula via oxidative stress that occurs after iron and hemosiderin release in the blood coagulation pathway [11, 12]. These oxidative stress effects can be demonstrated as early as 24 h after hemorrhage development. Another mechanism in which SRH can contribute to vision loss is clot retraction. Clot retraction can shear and damage the photoreceptors as well as separate them from the RPE causing atrophy and disciform scar formation [12]. Thus, early intervention in SRH is likely very important for preserving vision.

Although there are no standardized treatment protocols for SRH, both surgical and nonsurgical therapeutical approaches have been employed. Surgical approaches include pars plana vitrectomy (PPV) combined with multiple maneuvers such as manual subretinal clot removal, CNV lesion removal, macular translocation, RPE patch repair, SRH drainage, intravitreal injection of recombinant-tissue plasminogen activator (tPA), expansile gas and air displacement, and anti-vascular endothelial growth factor (anti-VEGF) injections. Nonsurgical therapeutic approaches include intravitreal anti-VEGF monotherapy, intravitreal tPA administration, intravitreal pneumatic displacement, and photodynamic therapy (PDT). This review article highlights the present management strategies, their strengths and weaknesses, for SRH in individuals with AMD, while also delving into diverse treatment modalities tailored to varying sizes of SRH (Table 1).

Table 1.

Advantages and limitations of different modalities for treatment of subretinal hemorrhage secondary to AMD

Different modalities to treat subretinal hemorrhageAdvantagesLimitations
Surgical approaches 
Pars plana vitrectomy with subretinal clot removal Improvement of visual acuity in large hemorrhagic lesions Risk of significant RPE atrophy and retinal detachment 
Pars plana vitrectomy with recombinant tissue plasminogen activator (tPA) Clinical improvement of visual acuity in medium/large-sized hemorrhages Risk of retinal detachment, cataract progression, recurrent bleeding, and development of subretinal fibrosis after surgery 
Pars plana vitrectomy with a combination of pneumatic gas and/or air displacement and subretinal tissue plasminogen activator (tPA) administration High efficacy in displacing subretinal blood completely in large subretinal hemorrhage while improving visual acuity Risk of rhegmatogenous retinal detachment 
Limited data to comment on the efficacy in small-sized SRHs 
Pars plana vitrectomy with multiple procedures involving the addition of anti-VEGF therapy Prevention of disease progression and preservation of visual acuity after surgery Inferior to tPA injection intraoperatively for treatment of large-sized SRH 
Greater VA improvement in 6 months compared to PPV without anti-VEGF therapy 
Pars plana vitrectomy with multiple procedures involving the addition of subretinal implant of human amniotic membrane Similar VA improvements in large hemorrhages compared to subretinal tPA injection Similar postoperative complications with PPV with subretinal tPA administration 
Significant benefit in inhibiting CNV recurrence 
Nonsurgical approaches 
Subretinal tissue plasminogen activator (tPA) administration without vitrectomy Effective only when employed in conjunction with a surgical approach Risk of retinal toxicity 
No protection against retinal damage 
Failure of diffusion through neural retina to access subretinal clot 
Intravitreal anti-vascular endothelial growth factor monotherapy Less procedurally complex than surgery, with minimal pain, and a low incidence of complications Limited effectiveness on treatment for large-sized SRHs 
Significant benefit in small- and medium-sized SRHs 
Photodynamic therapy with verteporfin Stable vision for over 12 months in eyes with CNV and SRH associated with AMD Limited data on effectiveness on different types of subretinal hemorrhage; data mostly suggest its efficacy in treatment of AMD 
Different modalities to treat subretinal hemorrhageAdvantagesLimitations
Surgical approaches 
Pars plana vitrectomy with subretinal clot removal Improvement of visual acuity in large hemorrhagic lesions Risk of significant RPE atrophy and retinal detachment 
Pars plana vitrectomy with recombinant tissue plasminogen activator (tPA) Clinical improvement of visual acuity in medium/large-sized hemorrhages Risk of retinal detachment, cataract progression, recurrent bleeding, and development of subretinal fibrosis after surgery 
Pars plana vitrectomy with a combination of pneumatic gas and/or air displacement and subretinal tissue plasminogen activator (tPA) administration High efficacy in displacing subretinal blood completely in large subretinal hemorrhage while improving visual acuity Risk of rhegmatogenous retinal detachment 
Limited data to comment on the efficacy in small-sized SRHs 
Pars plana vitrectomy with multiple procedures involving the addition of anti-VEGF therapy Prevention of disease progression and preservation of visual acuity after surgery Inferior to tPA injection intraoperatively for treatment of large-sized SRH 
Greater VA improvement in 6 months compared to PPV without anti-VEGF therapy 
Pars plana vitrectomy with multiple procedures involving the addition of subretinal implant of human amniotic membrane Similar VA improvements in large hemorrhages compared to subretinal tPA injection Similar postoperative complications with PPV with subretinal tPA administration 
Significant benefit in inhibiting CNV recurrence 
Nonsurgical approaches 
Subretinal tissue plasminogen activator (tPA) administration without vitrectomy Effective only when employed in conjunction with a surgical approach Risk of retinal toxicity 
No protection against retinal damage 
Failure of diffusion through neural retina to access subretinal clot 
Intravitreal anti-vascular endothelial growth factor monotherapy Less procedurally complex than surgery, with minimal pain, and a low incidence of complications Limited effectiveness on treatment for large-sized SRHs 
Significant benefit in small- and medium-sized SRHs 
Photodynamic therapy with verteporfin Stable vision for over 12 months in eyes with CNV and SRH associated with AMD Limited data on effectiveness on different types of subretinal hemorrhage; data mostly suggest its efficacy in treatment of AMD 

A PubMed review was conducted to search for English-language studies spanning from 1990 to August 2023. The search involved key terms such as “subretinal hemorrhage,” “pars plana vitrectomy,” “anti-VEGF monotherapy,” “tPA,” “age-related macular degeneration,” “pneumatic displacement,” and others. The inclusion criteria encompassed clinical trials, case reports, and reviews that provided specific descriptions of treatment methods. Two independent reviewers (D.O. and D.O.) carried out the initial phase, where all identified titles and abstracts were assessed for their relevance in managing SRH secondary to AMD. In the subsequent phase, potentially pertinent articles underwent full-text screening. The final selection included articles that discussed the advantages and limitations of particular treatment approaches. In the event of any disagreement, a third, experienced reviewer (M.O.) was consulted to reach a consensus.

Prior to the advent of intravitreal pharmacotherapy, surgical intervention for SRH in AMD was the main treatment modality. Within this category, diverse surgical approaches have emerged including PPV with clot or CNV membrane removal, PPV in conjunction with intravitreal or subretinal tPA, PPV combined with pneumatic gas and/or air displacement along with tPA, PPV combined with anti-VEGF therapy, and PPV featuring subretinal implantation of human amniotic membrane (hAM).

Before discussing the detailed categories of surgical interventions, it is pertinent to highlight key studies conducted in the realm of surgical treatment for varying sizes of SRH. Mun et al. [13] contrasted surgical approaches against nonsurgical methodologies and reported for small-sized SRHs, the anti-VEGF monotherapy group exhibited notably improved best-corrected visual acuity (BCVA) at both 3 and 6 months when compared to the other groups (comprising subretinal surgery and nonsurgical gas tamponade). Conversely, among patients with SRH size >4 DD, the mean BCVAs at the 12-month mark displayed no significant differences across these three groups (anti-VEGF monotherapy, nonsurgical gas tamponade, and subretinal surgery) [13]. These results suggest anti-VEGF monotherapy as a reasonable approach for small-sized SRH.

Furthermore, regarding the distinct subset of massive SRH, Fine et al. [14] noted the median BCVA progressed from hand motions to count fingers 3 months after the surgical intervention. Nevertheless, it is noteworthy that over 50% of the patients who initially underwent surgery needed an extra surgical intervention due to vitreous hemorrhage [14]. Lastly, Wilkins et al. [15] demonstrated that the location of hemorrhage (subretinal pigment epithelium hemorrhage vs. SRH) did not show a significant difference in visual acuity (VA) improvement in the surgical treatment of SRH. The subgroups within the surgical treatment choices encompass the following.

PPV with Subretinal Clot Removal

Various surgical interventions have been utilized to manage SRH in AMD, including the direct removal of subretinal blood clots. Machemer proposed surgical removal of the submacular blood clot through a retinotomy in the late 1970s but was abandoned due to poor functional outcome and possible complications [16‒19]. The maneuver increased the risk of significant RPE atrophy [16, 20‒22], and the procedure was frequently complicated by retinal detachment (30–37%) given the large retinotomy created in the posterior pole [16, 21]. The Submacular Surgery Trial (SST), the largest relevant surgical comparative randomized controlled trial reported to date, compared direct clot removal to observation as the study was conducted prior to the advent of anti-VEGF therapy [23]. The investigators found that clot evacuation did not stabilize or enhance vision and carried a high risk of rhegmatogenous retinal detachment (RRD) [23]. Within the surgery group, the eyes with tPA administration (62 eyes) revealed no significant difference in VA outcomes. In the surgery group, 24 of 30 RRDs occurred in eyes that had lesion sizes >16 disc areas. This study underscores the potential risks associated with subretinal surgical maneuvers large hemorrhagic lesions.

PPV with Recombinant tPA

For nearly 2 decades, tPA use has become more widespread in the treatment of patients with acute SRH [20, 24, 25]. This 527-amino acid polypeptide catalyzes the breakdown of plasminogen to plasmin, the latter being the principal enzyme involved in the lysis of clots [20]. tPA use was introduced in the 1990s to aid in the liquefaction of blood clots and reduce the surgical trauma associated with PPV [26, 27]. Lewis et al. [26, 27] reported successful clot liquefaction was achieved in approximately 70–80% of cases. While functional improvement was observed in 60–80% of patients, the postoperative VA remained below 20/200 in most cases [26]. Some studies that were small in scale reported initial improvement in VA, but many patients experienced significant complications after the surgery, including retinal detachment, cataract progression, recurrent bleeding, and development of subretinal fibrosis [28‒32]. While no consensus exists on the superiority of vitrectomy on SRH management, a recent 2023 study compared PPV with tPA to in-office pneumatic displacement with tPA and showed that PPV was not superior nor added benefits for SRH secondary to nAMD at 3 months after adjustment of SRH size [8]. Patients with SRH smaller than 2 DD were excluded. Of all the patients, 64% had SRH diameter between 2 and 5 DD (small/medium-sized) and 29% had SRH diameter higher than 5 DD (large-sized). Both treatment strategies lead to a clinical improvement of VA without safety concerns for SRH over 6 months [8].

PPV with a Combination of Pneumatic Gas and/or Air Displacement and Subretinal tPA Administration

In 2001, Haupert et al. [32] proposed a surgical approach that combined pneumatic displacement with subretinal tPA administration, minimizing manipulation of the retina and RPE. In the study, PPV was performed in 11 eyes, and a microcannula was used to inject 25–50 μg of tPA into the subretinal space. This was followed by an immediate exchange of fluid with air or gas (sulfur hexafluoride, SF6) and postoperative prone head positioning. This study yielded results comparable to more invasive approaches and showed modest visual improvements in several patients. However, this study did not categorize the thickness of SRHs. After this study was published, multiple following reports demonstrated visual improvements as well [24, 25, 33, 34]. Furthermore, Lincoff et al. [35] explored the efficacy of a 40-degree gaze-down position as an alternative to face-down positioning in these approaches, finding it to be equally effective and more tolerable for patients. A recent study performed in 2022 also confirmed the promising efficacy of PPV combined with tPA and gas tamponade for displacing subretinal blood in patients presenting with a large SRH (mean SRH was 6.2 DD) [20]. In this study, complete displacement was achieved in almost 90% of patients within 1 month.

Moreover, Oshima et al. [29] reported for patients with massive SRH that pre-operative intravitreal tPA injection with subsequent PPV and long-acting gas tamponade improved the VA of 88% of patients to 20/400 or better. Chang et al. [36] also concluded that PPV with subretinal tPA injection and gas tamponade was effective for the displacement of large SRH while also improving VA. However, they also found VA loss over time and noted the addition of postoperative anti-VEGF injection may improve and maintain VA gains [36]. An observed side effect of this treatment modality is RRD where a recent case series calculated its occurrence at a rate of 7% [37]. Overall, if surgery is pursued for large SRH, PPV combined with subretinal tPA injection and intraocular gas tamponade is frequently performed with a relatively high success rate, ranging from 64 to 100%, for complete SRH displacement [32, 38‒42].

Martel et al. [43, 44] reported a surgical technique of adding subretinal air in addition to subretinal tPA air to facilitate displacement of SRH. With this technique, subretinal air is expected to localize at the submacular space above subretinal fluid due to its buoyancy, thus protecting the macula from being reoccupied by the original hemorrhage. This hypothetically leads to a more efficient downward displacement of SRH and prevents any unintentional shifting of the hemorrhage toward the fovea. Abdulaal et al. [45] supported these findings and showed that pneumatic displacement of submacular hemorrhage (SMH) using subretinal air, without the need for tPA, achieved a remarkable success rate. Specifically, this approach resulted in complete blood displacement in 92% of massive SRH cases [45]. As a result, subretinal air may be a valuable tool for surgeons to rapidly and effectively move massive SRH when necessary. There is still a paucity of data on these maneuvers for small-sized SRH.

PPV with Multiple Procedures Involving the Addition of Anti-VEGF Therapy

Due to the presence of CNV primarily associated with AMD, the long-term visual stability in cases of SMH relies heavily on controlling the underlying disease [25, 46, 47]. As a result, researchers have explored the use of adjuvant postoperative anti-VEGF therapy in surgical treatments for SMH. Some case reports have shown positive outcomes when intravitreal anti-VEGF injections are administered either during pneumatic displacement alone or after PPV (Fig. 4) [48, 49].

Fig. 4.

Same patient as Figure 3. Pre- and postoperative color photographs of a case with subretinal hemorrhage before (a) and 1 day after (b) 25 g PPV + subretinal injection of TPA + intravitreal bevacizumab + SF6 to clear out the submacular hemorrhage. Visual acuity remained at counting fingers due to a disciform scar but the SRH was successfully displaced.

Fig. 4.

Same patient as Figure 3. Pre- and postoperative color photographs of a case with subretinal hemorrhage before (a) and 1 day after (b) 25 g PPV + subretinal injection of TPA + intravitreal bevacizumab + SF6 to clear out the submacular hemorrhage. Visual acuity remained at counting fingers due to a disciform scar but the SRH was successfully displaced.

Close modal

A recent comprehensive study conducted by Chang et al. [36] examined 100 cases of SMH treated with PPV, subretinal tPA, intravitreal gas, with or without postoperative anti-VEGF injections and found that 82% of eyes experienced an improvement in postoperative VA. Approximately 40% of the cases received anti-VEGF therapy and demonstrated greater VA improvement 6 months after surgery compared to those without anti-VEGF injections [36]. The researchers concluded that incorporating anti-VEGF treatment may help prevent disease progression and maintain the visual gains achieved through initial SMH removal.

Furthermore, Iglicky et al. [50] compared visual and anatomical outcomes between subretinal aflibercept and intravitreal aflibercept in the context of PPV, pneumatic gas displacement with subretinal air, and subretinal tPA in patients with naïve SRH secondary to nAMD. This study showed better management of the CNV, with a statistically significant lower need for anti-VEGF injections when treated with subretinal aflibercept compared to intravitreal application [50].

In addition, there have been studies conducted to explore the utilization of anti-VEGF injections for the treatment of medium or large-sized SRH. Stanescu-Segall et al. [9] demonstrated that in cases involving a large SRH, subretinal tPA injection led to superior anatomical and visual outcomes when compared to intravitreal anti-VEGF injections intraoperatively. Indeed, the majority of the existing literature tends to favor the application of subretinal tPA over anti-VEGF intraoperatively for the treatment of large SMHs [51‒53]. Only two studies thus far showed equivalent outcomes between these two different techniques [54, 55].

Although previous studies have mostly shown that tPA injection is superior to intraoperative intravitreal anti-VEGF injections in large SRH, a co-application of tPA and anti-VEGF is commonly chosen to maintain the treatment effects in large SRH [56]. Treumer et al. [53] evaluated the short-term and long-term outcomes of subretinal co-application of tPA and bevacizumab followed by intravitreal injections of bevacizumab. This approach showed successful complete displacement of small and large SMH in 85% of the patients. Not only did this study reveal the advantages of concurrently administering tPA and anti-VEGF, but it also underscored the importance of postoperative application of anti-VEGF to enhance visual improvement. Additional studies have reported comparable findings, utilizing postoperative anti-VEGF injections with minor adjustments in surgical methods [36, 57].

PPV with Multiple Procedures Involving the Addition of Subretinal Implant of hAM

The hAM serves as the innermost layer of the fetal membranes [58]. It consists of a stromal matrix, a thick collagen layer, and a basement membrane covered by a single layer of epithelium. The transplantation of the amniotic membrane has been used for the treatment of ocular surface abnormalities [58, 59].

Caporossi et al. [54] evaluated the different postoperative outcomes of patients affected by CNV complicated by massive SRH that underwent subretinal implant of hAM or subretinal injection of tPA. They reported that both techniques had similar VA improvements and postoperative complications [54]. However, transplantation of hAM seemed to have a significant benefit in inhibiting CNV recurrence.

Subretinal tPA Administration without Vitrectomy

There have been studies that also administered intravitreal tPA monotherapy or administered prior to surgery. In 1996, Heriot et al. [60] introduced a new technique for lysing and displacing submacular blood without the need for intraocular surgery. This approach involved injecting tPA and a bubble of long-acting expansile gas into the vitreous cavity, known as pneumatic displacement. Although successful displacement of submacular blood has been reported by several previous studies, there were instances of retinal toxicity observed with a tPA dosage of 100 µg [25, 60]. No retinal pigmentary changes or unexplained visual loss were observed when a lower dose of tPA (18–50 µg) was administered [61].

Furthermore, a prior experimental animal study conducted on rabbits showed that injecting tPA intravitreally into rabbits 1 day after the formation of a subretinal blood clot resulted in the complete disappearance of the formed subretinal clot [62]. Although tPA led to a faster resolution of hemorrhage, it did not confer protection against retinal damage [62]. Notably, the study highlighted the necessity for surgical drainage to remove the liquified blood resulting from clot lysis. The study suggested that in situations where postponing vitrectomy is required, the early fibrinolysis facilitated by tPA could serve to degrade fibrin. On the other hand, a separate study noted that the intravitreal application of tPA in rabbits led to only partial clot lysis which proved insufficient for clot removal through aspiration alone [63]. Moreover, Kamei et al. [64] experiment on pigs demonstrated that intravitreal tPA failed to diffuse through the intact neural retina to access the subretinal clot. Overall, the evidence suggests that the use of tPA is most effective when employed in conjunction with a surgical approach to access the subretinal space, rather than as a standalone treatment method.

Intravitreal Anti-VEGF Monotherapy

The use of intravitreal anti-VEGF agents is common in the treatment for neovascular AMD (nAMD) as well as other eye diseases such as polypoidal choroidal vasculopathy, proliferative diabetic retinopathy, and CNV resulting from traumatic choroidal rupture [10, 65‒67]. Compared to other treatment options for SRH, anti-VEGF monotherapy offers an advantage of being less procedurally complex than surgery, with minimal pain, and a low incidence of complications [20]. Maintaining a specific posture is not required, allowing patients to resume daily activities immediately after treatment.

During the initial introduction of ranibizumab and aflibercept, previous clinical trials such as the ANCHOR and MARINA excluded eyes with SRH [68‒70]. Previous studies reported that the use of intravitreal anti-VEGF monotherapy showed improvements in patients with SRH related to nAMD [71‒74]. Kim et al. [75] demonstrated the beneficial effects and reduced invasiveness of intravitreal anti-VEGF treatments, such as ranibizumab and aflibercept, in patients with SRH secondary to nAMD. This study was the largest case series to evaluate the efficacy of anti-VEGF monotherapy in the treatment of AMD accompanied by SMH. It had similar or even better VA outcomes compared to other publications done on surgical approaches [23, 75]. Furthermore, the study emphasized the limited effectiveness of anti-VEGF treatment for large-sized SRHs and underscored the necessity for more assertive treatment strategies in such cases.

Another study demonstrated that patients who successfully completed the follow-up period without encountering vitreous hemorrhages experienced noteworthy enhancements in VA through the administration of aflibercept and brolucizumab. These results were consistent with earlier research [76]. Moreover, several studies demonstrated VA improvement with the use of monthly anti-VEGF monotherapy in patients with SRH, with the most significant benefit in eyes with flat or small- to medium-sized hemorrhages [20, 67, 71, 75, 77].

Shin et al. [78] demonstrated that the combined approach of pneumatic displacement along with anti-VEGF treatment could potentially yield a synergistic effect. This arises from the notion that reducing hemorrhage thickness through pneumatic displacement might augment the penetration of the anti-VEGF agent into the CNV lesion [78].

Among the various treatment options for SRH associated with nAMD, including pneumatic displacement or PPV, anti-VEGF agents might be the most important because anti-VEGF can treat the underlying pathologic CNV. Examining the findings of the preceding studies, it is reasonable to conclude that anti-VEGF injections are generally efficacious for achieving short-term improvements in VA, particularly in cases where patients have intermediate baseline VA and small-sized SRH.

As of now, there are no randomized controlled trials that have assessed the efficacy of anti-VEGF monotherapy for SRH secondary to AMD compared to the various surgical methods. An ongoing European Phase 3 trial called TIGER is designed to evaluate the effectiveness of anti-VEGF monotherapy in comparison to a combination of anti-VEGF monotherapy and surgical intervention. The anticipated completion date for this trial is set for the year 2025 [79].

PDT with Verteporfin

PDT involves the utilization of a photosensitizing dye to convert light into chemical energy, leading to the release of free radicals [80]. This process specifically targets and obstructs blood vessels at the site of interest, causing the destruction of cells while minimizing harm to nearby tissues [81, 82]. The ophthalmology field embraced PDT in the early 1990s, utilizing verteporfin, an intravenously administered photosensitizing dye, combined with low-power, long-duration infrared laser application [20, 83]. PDT is employed to induce the occlusion of abnormal microvasculature in CNV and choroidal tumors [83, 84]. Initially, PDT was primarily used for CNV secondary to AMD [81, 85, 86]. However, it has now become a secondary option following anti-VEGF therapy. Despite this shift, the initial success of PDT has motivated further investigation into its potential for treating various posterior segment pathologies.

PDT with verteporfin is approved for predominantly classic CNV associated with AMD [85‒87]. Ahmad et al. [81] conducted a study demonstrating that PDT can effectively minimize visual loss in eyes affected by neovascular AMD, particularly those with predominantly hemorrhagic lesions. Similarly, Bakri et al. [88] found that PDT treatment resulted in stable vision for over 12 months in eyes with CNV and SRH associated with AMD.

SRH is an ocular condition that poses a significant risk to vision and is most commonly associated with CNV due to AMD. The progression of SRH is typically unfavorable, prompting the exploration of various surgical and nonsurgical treatment approaches depending on the severity of SRH. In an effort to minimize invasiveness, office-based nonsurgical procedures have been utilized, including tPA with pneumatic displacement, anti-VEGF injections, and PDT. These nonsurgical approaches may offer improvements and maintenance of VA.

On the other hand, surgical maneuvers during PPV, with or without the administration of tPA and anti-VEGF injections, have also been utilized in the management of SRH. These surgical approaches have demonstrated reasonable effectiveness in treating SRH in AMD. When contrasting surgical and nonsurgical approaches across varying baseline sizes of SRH, the research tends to lean toward favoring anti-VEGF treatments for cases involving small-sized SRHs. On the other hand, surgical treatment modalities have exhibited promising outcomes in addressing large-sized SRHs. Even with the implementation of surgery, it is still crucial to address the underlying disease, particularly AMD. The addition of postoperative anti-VEGF injections has shown promise in preserving vision over an extended period of time. It is important to highlight that visual outcomes in patients with SRH can vary significantly, underscoring the complexity of the condition. Nevertheless, these treatment strategies hold the potential to enhance vision and improve the quality of life for certain patients afflicted by SRH in AMD.

The authors declare that there is no conflict of interest.

This manuscript received no funding.

Murat Oncel reviewed the literature. Damla Oncel and Deniz Oncel reviewed the literature and wrote the first draft under the guidance of the corresponding author (J.F.A.). Kapil Mishra performed extensive revisions of the manuscript. J.F.A. reviewed several versions of the manuscript.

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