Efficacy and Safety of Anti-VEGF Injections and Surgery for AMD-Related Submacular Hemorrhage: A Systematic Review & Meta-Analysis.

TOPIC: This systematic review and meta-analysis investigates the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) injections compared to surgical intervention in improving visual acuity (VA) and reducing complications for patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD). CLINICAL RELEVANCE: Determining the optimal intervention for SMH in AMD is crucial for patient care. METHODS: We included studies on anti-VEGF injections or surgical interventions for SMH in AMD from 7 databases, searched up to May 2024. Data extraction and quality assessment were done by two independent reviewers. Certainty of evidence was assessed GRADE approach. Meta-analysis employed random-effects models. Primary outcomes were pooled mean logMAR VA difference (initial examination minus last follow-up VA) and adverse events rates. RESULTS: A total of 43 observational studies were included: 21 (960 eyes) on anti-VEGF and 22 (455 eyes) on surgery. Comparisons were made across separate studies due to lack of head-to-head studies. Meta-analysis included 11 anti-VEGF studies (444 eyes) and 12 surgical studies (195 eyes) for VA outcomes. The mean difference (MD) in VA was -0.16 (95%CI: -0.26,-0.07) for anti-VEGF and -0.36 (95%CI: -0.68,-0.04) for surgery, with no significant difference between groups (X2=1.70, df =1, p=0.19). Heterogeneity was high in surgical studies (I2=96.2%, tau2=0.23, p<0.01) and negligible in anti-VEGF studies (I2=7%, tau2=0.003, p=0.38). GRADE certainty was moderate for anti-VEGF and low for surgery. Anti-VEGF had lower rates of cataract (0% vs 4.6%), proliferative vitreoretinopathy (PVR, 0.1% vs 2.0%), and retinal detachment (RD, 0.1% vs 10.6%), but similar rates of recurrent hemorrhage (5.4% vs 5.3%). Complications were summarized descriptively due to zero cell problem. CONCLUSION: Both anti-VEGF and surgery treat SMH in AMD with similar VA outcomes but different safety profiles. Anti-VEGF is preferred for less severe hemorrhage, while surgery is suited for extensive hemorrhage. Despite uncertain comparative VA outcomes, treatment should be guided by clinical judgment and patient factors.

Long-term follow-up of a patient with partial optic nerve avulsion associated with submacular hemorrhage who underwent pneumatic displacement.

Purpose: We report the case of a 16-year-old boy with partial optic nerve avulsion (ONA) and submacular hemorrhage (SMH) resulting from blunt ocular trauma who underwent pneumatic displacement and subsequent monitoring with optical coherence tomography (OCT) and fundus photography. Observations: Reduced visual acuity was observed in the right eye at presentation (20/2400). Vitreous hemorrhage, partial ONA, and SMH were observed during dilated fundus examination. SMH was managed via pneumatic displacement. Subsequent examination revealed improvement in the visual acuity of the right eye with a substantial reduction in the subfoveal hemorrhage. Further improvement in visual acuity was observed 6 months after the injury (20/150). A smaller optic nerve head excavation defect, foveal atrophy, and reabsorption of SMH were observed during fundus examination. OCT of the optic nerve revealed that glial growth had covered the avulsion excavation. However, atrophy of the outer retinal layer of the fovea was observed during macular OCT. Conclusions and importance: This case emphasizes the importance of performing multimodal imaging in cases of ONA as it enables the identification of alterations in the retinal layers and optic nerve. The subretinal hemorrhage was displaced from the subfoveal region without any adverse effects.

Efficacy of anti-VEGF intravitreal injection in traumatic submacular hemorrhage: a retrospective study.

OBJECTIVE: In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage. METHODS: A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging. RESULTS: The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64 years, with an average age of 38.1 years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51). CONCLUSION: Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.

Influence of submacular hemorrhage at baseline on the long-term outcomes of aflibercept treatment for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To investigate the influence of submacular hemorrhage (SMH) at baseline on long-term visual outcomes of patients with typical age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept (IVA). METHODS: In this retrospective study, eyes of treatment-naïve patients with tAMD and PCV who initiated IVA under a treat-and-extend regimen and were followed up for ≥ 5 years were classified into the tAMD-SMH ( +), tAMD-SMH (-), PCV-SMH ( +), and PCV-SMH (-) groups based on the presence of SMH at baseline. Best-corrected visual acuity (BCVA) changes and macular fibrosis and atrophy incidences were assessed. RESULTS: This study included 127 eyes (127 patients), including 51 with tAMD and 76 with PCV; 18 eyes had SMH at baseline. In the tAMD-SMH ( +) group (n = 6), the mean logMAR BCVA significantly deteriorated from 0.59 ± 0.45 at baseline to 0.88 ± 0.47 at the final visit (P = 0.024). No significant BCVA changes were observed in the tAMD-SMH (-) (n = 45), PCV-SMH ( +) (n = 12), or PCV-SMH (-) (n = 64) groups (all P > 0.05). The tAMD-SMH ( +) group showed a significantly higher incidence of macular fibrosis at the final visit than did the tAMD-SMH (-) group (P = 0.042). There was no influence of baseline SMH on the macular fibrosis incidence in eyes with PCV and the macular atrophy incidence in eyes with tAMD and PCV. CONCLUSION: The presence of SMH at baseline resulted in poorer long-term visual acuity in eyes with tAMD, even with aflibercept treatment. However, no such influence was observed in eyes with PCV.

Therapeutic effect of subretinal injection of alteplase plus Conbercept for acute submacular hemorrhage secondary to polypoid choroidal vasculopathy / 中华眼底病杂志

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Fundus Autofluorescence Patterns in Subretinal Hemorrhages Associated with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: Submacular hemorrhage (SMH) is a vision-threatening complication of neovascular age-related macular degeneration (AMD). The exact treatment scheme is not established yet. The aim of the current study was to describe surgical results and fundus autofluorescence (FAF) patterns after pars plana vitrectomy (ppV) + subretinal tissue plasminogen activator (tPA) + anti-vascular endothelial growth factor (VEGF) and intravitreal tPA + anti-VEGF + sulfur hexafluoride (SF6) tamponade and to compare them to intravitreal tPA + anti-VEGF + SF6 in the treatment of SMH in the course of AMD. MATERIALS AND METHODS: We performed FAF imaging in patients with a previous SMH in the course of AMD with a duration of <60 days treated with vitrectomy with subretinal anti-VEGF and tPA and intravitreal anti-VEGF, tPA, and SF6 administration (group 1) or intravitreal tPA + anti-VEGF + SF6 (group 2). In all eyes, a throughout ophthalmic examination, fluorescein angiography, and spectral domain optical coherence tomography (SD-OCT) were done for diagnosis. SD-OCT was performed monthly during treatment. RESULTS: Three FAF patterns were observed in both groups. Pattern one (normal autofluorescence) was observed in 5/18 in group one and 5/21 group two. Pattern two was observed in 6/18 in group one and 7/21 in group two. Pattern three was noted in 7/18 in group one and 5/21 in group two. Improvement in visual acuity was statistically significant for both groups: 0.01 Snellen (2.0 logMAR) to 0.11 Snellen (0.96 logMAR) in group one (p = 0.019) and 0.11 Snellen (0.96 logMAR) to 0.33 Snellen (0.48 logMAR) in group two (p = 0.0007). Central retinal thickness also decreased with statistical significance for both groups (p < 0.05). CONCLUSION: FAF patterns did not depend on the treatment used, but solely on the duration of SMH before treatment. SMH if not treated prompt enough might cause long-standing photoreceptor and retinal pigment epithelium defect, which is represented by hypo- and hyperautofluorescence. Performing a subretinal injection of tPA and anti-VEGF does not cause any defects associated with the injection site. That might be associated with previous local internal limiting membrane peeling, which reduces the injection pressure. Not only prompt treatment of SMH but also further continuation of anti-VEGF treatment is mandatory to maintain vision.

A Case of Traumatic Submacular Hemorrhage Treated with tPA and Pneumatic Displacement.

This is a case of a 31-year-old female who presented to the emergency department at a London teaching hospital with a 24-h history of visual loss following an assault. The ophthalmological routine examination showed a submacular hemorrhage (SMH), and a computerized tomography scan demonstrated a displaced orbital floor fracture with inferior rectus entrapment and a medial wall fracture. To induce displacement of the SMH, intravitreal injection of 0.25 µg tissue plasminogen activator (tPA) was combined with 0.3 mL of intravitreal 100% perfluoropropane (C3F8) gas. At the 1-day follow-up, there was an inferotemporal displacement of the blood clot, and visual acuity improved from hand motions to 6/5 within 3 months. No complications occurred over 2 years of follow-up, with a final visual acuity of 6/5. This case shows us that intravitreal tPA and gas appear safe and effective as a treatment for traumatic SMHs. Furthermore, our results demonstrate that prompt treatment leads to favorable anatomical and functional outcomes.

[Vitreoretinal surgery in age-related macular degeneration]. / Vitreoretinale Chirurgie bei altersabhängiger Makuladegeneration.

The structure of the vitreous body, its interaction with the retinal surface and tractive alterations of the vitreoretinal interface may play a role in the pathogenesis and the development of age-related macular degeneration (AMD). From clinical trials it can be concluded that posterior vitreous detachment (PVD) or vitreous removal may protect against the development of neovascular AMD. Vitreomacular adhesions may promote neovascular AMD and may have an impact on the efficacy and frequency of intravitreal vascular endothelial growth factor (VEGF) inhibition. Therefore, vitreomacular surgery may be considered as a treatment option in selected cases. Peeling of epimacular membranes and the internal limiting membrane (ILM) may contribute to stabilizing visual acuity and reducing the treatment burden of current intravitreal pharmacotherapy. At present, surgical interventions in AMD are mainly performed in cases of submacular hemorrhage involving the fovea. The treatment is not standardized and consists of liquefaction of the blood using recombinant tissue plasminogen activator (rTPA) and its pneumatic displacement, potentially combined with VEGF inhibition. Other submacular surgical strategies, such as choroidal neovascularization (CNV) extraction, macular translocation or transplantation of retinal pigment epithelium (RPE) are currently limited to selected cases as a salvage treatment; however, the development of these submacular surgical interventions has formed the basis for new approaches in the treatment of dry and neovascular AMD including submacular or intravitreal gene and stem cell therapy.

Prognostic factors for visual acuity improvement after treatment of submacular hemorrhage secondary to exudative age-related macular degeneration.

PURPOSE: To recognize prognostic factors for better final visual acuity (VA) in patients presenting with submacular hemorrhage (SMH) secondary to exudative age-related macular degeneration. METHODS: This retrospective study included patients who presented to a tertiary ophthalmology department between 2012 and 2019 with SMH and were treated by pars plana vitrectomy (PPV) or injection of tissue plasminogen activator (tPA) with pneumatic displacement. Baseline characteristics included demographic data, VA and optical coherence tomography (OCT) characteristics of the SMH. Patients were divided into groups by improvement of at least 2 lines in BCVA (best corrected visual acuity), and by having a final BCVA better than 20/200. RESULTS: Forty-three eyes of 43 patients were included. Mean age was 86.72 ± 7.18. Prognostic factors for final VA better than 20/200 included better VA at presentation (1.25 vs 1.90 logMAR, p < 0.001), smaller area of SMH in the infra-red image (19.47 mm2 vs 38.45 mm2, p = 0.024), and lower height of SMH as measured by OCT (713.5 µm vs 962.5 µm, p = 0.03). Third of the patients improved in ≥2 lines from presentation, all in the group of the pneumatic and TPA displacement. CONCLUSION: Smaller SMHs with good VA at presentation have a better chance for improvement and result in a better final VA. These patients may benefit the most from pneumatic displacement of the SMH with intravitreal tPA and gas.

The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications.

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

Removal of Sub-Internal Limiting Membrane Hemorrhage Secondary to Retinal Arterial Macroaneurysm Rupture: Internal Limiting Membrane Non-Peeling Technique.

The appropriate surgical technique to improve the closure rate of perioperative full-thickness macular hole (FTMH) secondary to submacular hemorrhage (SMH) with sub-internal limiting membrane (ILM) hemorrhage caused by retinal arterial macroaneurysm (RAM) rupture remains an unsolved clinical problem. Several ILM transplantation techniques have been attempted, but these are challenging. Our new technique can remove sub-ILM hemorrhage with the central fovea ILM intact, without peeling the ILM. The medical records of three eyes from three patients with SMH and sub-ILM hemorrhage secondary to RAM rupture were retrospectively reviewed. During the surgery, a small ILM fissure was made outside the central fovea with ILM forceps, and sub-ILM hemorrhage was washed out through it by manually spraying balanced salt solution. Sub-ILM hemorrhage removal was achieved successfully in all eyes, with no occurrences of FTMH or other complications. Best-corrected decimal visual acuity improved from 0.05 (Snellen equivalent (SE), 20/400), 0.05 (SE, 20/400), and 0.05 (SE, 20/400) preoperatively to 0.3 (SE, 20/63), 0.4 (SE, 20/50), and 0.15 (SE, 20/125) at 3 months postoperatively, respectively. This new technique may help keep the foveal ILM intact and prevent perioperative FTMH formation.

Real-world outcomes and complications of different surgical approaches for significant submacular haemorrhages.

Purpose: To evaluate the outcomes and complications after different surgical management of cases with significant sumacular hemorrhage (SMH) of size more than 4 disc diameter (DD). Methods: It was a retrospective interventional study. All consecutive 103 cases of significant SMHs were treated by vitrectomy and divided into three groups. In Group A (<4 weeks, confined to the macula or extending inferiorly, n = 62), vitrectomy, subretinal cocktail of tissue plasminogen activator (tPA), antivascular endothelial growth factor, and air with SF6 gas; in Group B (4-8 weeks, extending beyond macula, n = 31), subretinal tPA followed by SMH drainage either by retinotomy (Group B-1, n = 17) or by temporal 180-degree retinectomy (Group B-2, n = 14) with silicone oil (SO) tamponade; and in Group C (>8 weeks, extending beyond macula, n = 10), SMH removal with autologous retinal pigment epithelium (RPE)-Choroid patch graft transplantations with SO tamponade were performed. Parameters evaluated were best corrected visual acuity (BCVA), Optos, optical computerized tomography, and ultrasonography as required. Results: Significant visual improvement was seen from mean preoperative to mean postoperative BCVA in Group A (P < 0.001), Group B (P < 0.001), and Group C (P < 0.001). Postoperative complications were recurrent SMH (4.84% vs 12.90% vs 10%), vitreous hemorrhage (6.45%, GroupA), hyphema (4.84% vs 12.90% vs 10%), hypotony (nil vs 3.23% vs 20%), macular hole formation (6.45%, Group A), epiretinal membrane (16.13%, Group B), and retinal detachment (3.23%, Group A and 10%, Group C). Conclusion: Surgical approaches for significant submacular hemorrhage are visually awarding, though certain specific complications may arise.

Three-dimensional heads-up system assisted pars plana vitrectomy and subretinal recombinant tissue plasminogen activator injection for submacular hemorrhage.

BACKGROUND: To evaluate the outcomes of three-dimensional (3D) heads-up system assisted pars plana vitrectomy (PPV) and subretinal injection of recombinant tissue plasminogen activator (rt-PA) for submacular hemorrhage (SMH). METHODS: Medical records of SMH patients who underwent 3D heads-up system assisted-PPV and subretinal injection of rt-PA from June 2021 to January 2022 were reviewed. The main outcomes included best-corrected visual acuity (BCVA), SMH absorption, and perioperative complications. RESULTS: We finally included 18 SMH eyes, most of which happened secondary to polypoidal choroidal vasculopathy (PCV) (10, 55.56%), followed by retinal arterial microaneurysm (RAM) (5, 27.78%), traumatic retinopathy (2, 11.11%) and neovascular age-related macular degeneration (nAMD) (1, 5.56%). The greatest linear dimension (GLD) and height of SMH were 6538.17 ± 2533.11 µm and 937.36 ± 420.21 µm, respectively. After an average postoperative follow-up period of 131.06 ± 38.96 days, patients' BCVA improved significantly from 1.85 ± 0.62 to 1.14 ± 0.82 logMAR (P < 0.05). SMH was completely and partially absorbed in 9 (50.00%) and 6 (33.33%) eyes, with no occurrence of iatrogenic retinal break. However, 4 additional PPVs were performed to manage the postoperative SMH and/or vitreous hemorrhage (VH) recurrence (2, 11.11%) and retinal detachment (RD) occurrence (2, 11.11%). Preoperative BCVA was significantly correlated with postoperative BCVA in multiple linear regression analysis (P < 0.05), and hemorrhagic pigment epithelial detachment (PED) was significantly correlated with SMH and VH recurrence in univariate binary logistic regression analysis (P < 0.05). CONCLUSIONS: The 3D heads-up system assisted-PPV and subretinal injection of rt-PA were efficacious in eliminating SMH and improving visual prognosis with satisfactory safety profile, while caution should be taken for PCV patients with hemorrhagic PED and massive SMH.

Efficacy Evaluation of Tissue Plasminogen Activator with Anti-Vascular Endothelial Growth Factor Drugs for Submacular Hemorrhage Treatment: A Meta-Analysis.

Submacular hemorrhage (SMH) is the accumulation of blood in the macular area that can severely damage the macular structure and visual function. Recently, the intraocular administration of tissue plasminogen activator (TPA) with anti-vascular endothelial growth factor (anti-VEGF) drugs was reported to have a positive effect on SMH. This meta-analysis aimed to explore the efficacy and safety of the drug combination. We systematically searched the Web of Science, MEDLINE, EMBASE, and Cochrane Library databases and screened relevant full-length literature reports. The quality of the reports was assessed by two independent reviewers. The best-corrected visual acuity (BCVA) and foveal thickness (FT) were considered the main indicators of efficacy. RevMan 5.4 software was used for this meta-analysis. Twelve studies were analyzed, and the results showed that BCVA at 1 month (p < 0.001), 3 months (p < 0.001), 6 months (p < 0.001), and the last follow-up (p < 0.001) was improved relative to the preoperative value. The postoperative FT was lower than the preoperative FT (p < 0.001). No significant difference in efficacy was observed between subretinal and intravitreal TPA injections (p = 0.37). TPA with anti-VEGF drugs is safe for SMH treatment and can significantly improve BCVA and reduce FT.

Antiplatelet and anticoagulant therapy in patients with submacular hemorrhage caused by neovascular age-related macular degeneration.

PURPOSE: Patients with extensive submacular hemorrhage (SMH) caused by age-related macular degeneration (AMD) have a poor visual prognosis despite surgical intervention. Systemic blood-thinning drugs, which are commonly prescribed in the same age group, are known to increase the risk of severe hemorrhage in many parts of the body. This study aimed to investigate whether systemic blood-thinning drugs have an impact on the severity of SMH and if there are differences between the different types of blood-thinning medication. METHODS: We reviewed the medical records of patients who suffered from surgically treated SMH between 2020 and 2022. All patients received a full ophthalmologic examination upon presentation including best-corrected visual acuity (BCVA) and optical coherence tomography. Other characteristics that were recorded included size of hemorrhage, blood-thinning therapy, and reason for intake. RESULTS: A total of 115 patients with a mean age of 82 years were included in this retrospective analysis. Eighty-three patients (72.2%) were on blood-thinning therapy. The mean size of SMH was 32.01 mm2. Mean BCVA at initial presentation was 1.63 logMAR and 1.59 logMAR 1 year after surgery. The size of SMH was significantly larger in patients on blood-thinning medication (35.92 mm2 vs. 21.91 mm2) (p = 0.001) and their BCVA postoperatively was worse with 1.68 logMAR compared to 1.30 logMAR after 1 year (p = 0.503). Patients with vitamin K antagonists had larger SMH size and worse outcomes regarding BCVA compared to direct oral anticoagulants. CONCLUSION: Blood thinners in patients with AMD affect the severity of SMH. Consequently, the indication for their intake should be critically evaluated.

Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy.

PURPOSE: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months. RESULTS: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R2 = 0.171, P = 0.056) and a greater displacement of SMH (R2 = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001). CONCLUSIONS: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

Pars plana vitrectomy and subretinal tissue plasminogen activator for large exudative submacular hemorrhage: a case series.

BACKGROUND: To evaluate anatomical and functional outcomes of patients with large submacular hemorrhage (SMH) who treated by pars plana vitrectomy (PPV) in combination with subretinal tissue plasminogen activator (TPA) injection, intraocular gas tamponade, and with additional post-operative interventions. METHODS: Medical records of 9 patients who presented with large SMH secondary to age-related macular degeneration (AMD) and underwent PPV, subretinal TPA injection, and gas tamponade at Chiang Mai university hospital between January 2012 and January 2020 were reviewed. Collected data included preoperative visual acuity (VA), SMH extent and duration, intraoperation and post-operation complications, post-operative anatomical and VA responses, and the need for administer post-operation additional treatments. RESULTS: Overall, five patients were male and four patients were female with a mean (SD) age of 66.9 (7.7) years and a mean (SD) follow-up of 21.1 (16.1) months. A mean (SD) duration of SMH was 15.1 (10.9) days with a mean (SD) extent of SMH was 6.2 (3.4) disc diameters. At 1-month post-operation, complete SMH displacement was noted in eight (88.9%) patients. The mean (SD) VA significantly improved from LogMAR 1.9 (0.4) to 1.1 (0.4), (P = 0.004). During follow-up, eight patients (88.9%) were given additional therapy (anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy, or in combination). At final follow-up, a mean (SD) LogMAR VA of 0.9 (0.4) was significantly improved compared to baseline (P = 0.004). For intra- and post-operation complications, none developed intraoperative retinal break and retinal detachment. CONCLUSIONS: Vitrectomy with subretinal TPA injection, intraocular gas tamponade, and additional post-operation treatments provide benefit for anatomical and visual outcomes for patients with large SMH. It may consider as one of effective treatment in this group of patients.

Submacular Hemorrhage Following Aflibercept Intravitreal Injection: A Report of Two Cases.

Anti-vascular endothelial growth factor (anti-VEGF) injections are the most effective treatment for exudative age-related macular degeneration (AMD). However, both bevacizumab and ranibizumab have been reported to cause submacular hemorrhage (SMH) in the treatment of exudative AMD. Aflibercept has also been reported to cause SMH but only in the treatment of polypoidal choroidal vasculopathy and not exudative AMD. This case series presents two patients with exudative AMD who developed SMH after treatment with aflibercept injections. The first patient is an 84-year-old female with exudative AMD in both eyes who presented with SMH four days after an aflibercept injection in her right eye. The second patient is a 77-year-old female who presented with exudative AMD in her left eye and SMH one month following an aflibercept injection. This case series shows that SMH in patients treated for exudative AMD is a rare yet possible complication of aflibercept injection that requires further research to establish its incidence and risk factors.

Coughing-induced retinal pigment epithelial tear after trabeculectomy combined with pars plana vitrectomy.

Purpose: To report a case of retinal pigment epithelial (RPE) tear after trabeculectomy combined with pars plana vitrectomy (PPV). Observations: A 65-year-old man with neovascular glaucoma due to proliferative diabetic retinopathy presented with visual impairment and elevated intraocular pressure (IOP) in the right eye and underwent trabeculectomy combined with PPV. Three weeks after surgery, the best-corrected visual acuity (logarithm of minimal angle of resolution) improved from 3.0 to 0.30, and the IOP was controlled within normal limits. Four weeks after the surgery, he noticed visual impairment and ocular pain in the right eye after continuous coughing associated with asthma. Fundus examination revealed bullous retinal detachment, choroidal detachment, and submacular hemorrhage (SMH) due to a giant RPE tear at the posterior pole. Visual acuity worsened considerably to 1.7, while IOP was not elevated (6 mmHg). The patient received PPV with recombinant tissue plasminogen activator (rt-PA) and fluid/air exchange for internal tamponade and achieved anatomic retinal and choroidal attachments. Conclusions and importance: The acute increase in hydrostatic pressure in the choroidal interstitium due to continuous coughing induces an RPE tear. Vitrectomy with rt-PA and fluid/air exchange may be a favorable treatment for exudative retinal detachment and SMH due to RPE tears.

One-Year Outcome of Intravitreal Tissue Plasminogen Activator, Ranibizumab, and Gas Injections for Submacular Hemorrhage in Polypoidal Choroidal Vasculopathy.

This study investigated one-year outcomes of treatment with one session of intravitreal recombinant tissue plasminogen activator, ranibizumab, and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). An extended study of a previous prospective trial of this treatment modality in PCV patients was conducted in 64 patients (64 eyes). Early Treatment Diabetic Retinopathy Study (ETDRS) score, central retinal thickness (CRT), and central pigment epithelial detachment thickness (CPEDT) before and 1, 3, and 12 months after treatment were analyzed. Mean ETDRS score increased from 58 at baseline to 64 letters (p = 0.0122), CRT decreased from 543 to 192 µm (p < 0.0001), and CPEDT decreased from 161 to 103 µm (p = 0.0668) at 3 months and were maintained until 12 months. Complications requiring reoperation occurred within one month in four eyes. Recurrence was observed in 46 eyes (72%), and 1.6 ± 1.5 (0−7) intravitreal aflibercept injections were given pro re nata. Univariate and multivariate analyses identified CPEDT as the pre- and post-treatment factor affecting 12-month ETDRS score (p < 0.0001). Improved visual acuity stabilized 3 months after treatment. Although 72% of patients experienced recurrence, an average of 1.6 aflibercept injections/patient maintained visual acuity up to 12 months. CPEDT was the most important factor associated with visual outcome.