Article

Treatment of submacular hemorrhage with tissue plasminogen activator and pneumatic displacement in age-related macular degeneration

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Purpose To evaluate visual and anatomic outcomes following pars plana vitrectomy and intravitreal or subretinal tissue plasminogen activator for submacular hemorrhage in patients with age-related macular degeneration. Methods This was a retrospective study on patients with a minimum follow-up of 12 months undertaken at a tertiary referral center. Data collected include demographic details, visual and optical coherence tomography changes, surgical details, and complications. Surgical results were compared with patients who were age and lesion size matched and treated with anti-vascular endothelial growth factor injections alone. Results There were 36 patients in surgical and 18 patients in control group. Patients in surgical arm had pars plana vitrectomy, intravitreal tissue plasminogen activator with air 24 (67%), 6 (16%) with C3F8 gas, 1 (3%) with SF6 gas, 4 (11%) subretinal tissue plasminogen activator with air, and 1 (3%) with C2F6 as post-operative tamponade. Mean LogMAR in tissue plasminogen activator group at baseline was 1.56, and it was improved at all time points 1.06 at 1 month (p < 0.05), 0.91 at 6 months (p < 0.05), and 1.07 at 1 year (p < 0.05). Mean best corrected visual acuity in control group at baseline was 1.22LogMAR with no significant improvement at any time points: 1 month (1.27), 6 months (1.35), and 12 months (1.36). Complications included retinal detachment 5%, vitreous hemorrhage 7.5%, and cataract 19%. Conclusion Pars plana vitrectomy with intravitreal (or subretinal) tissue plasminogen activator and pneumatic displacement can offer better outcome in comparison to anti-vascular endothelial growth factor alone in patients with submacular hemorrhage secondary to age-related macular degeneration.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... It is possible that a smaller injection needle decreased complications such as vitreous hemorrhage and retinal detachment. In studies without subretinal air injection, similar complications including vitreous hemorrhage, retinal detachment, and SMH were reported 11,16,28 . In our study, the frequency of vitreous hemorrhage (15.4%), retinal detachment (15.4%), and recurrent SMH (7.7%) was comparable to previous reports 14 . ...
... In contrast to other studies using multiple techniques or procedures performed by multiple surgeons [28][29][30] , the operation was performed by a single experienced surgeon and the same technique was applied to all cases to ensure technical uniformity in this study. However, our study has several limitations. ...
Article
Full-text available
Submacular hemorrhage (SMH) can lead to devastating visual loss in patients with age-related macular degeneration. We retrospectively evaluated the surgical outcomes of vitrectomy with subretinal injection of tissue plasminogen activator, bevacizumab, and air in 13 cases. Visual prognosis, anatomical results obtained with optical coherence tomography (OCT), and their correlations were investigated. We analyzed OCT parameters including SMH height, pigment epithelial detachment (PED) height and width, and status of ellipsoid zone (EZ) line. Complete displacement of SMH was achieved in 12 eyes. At 3 months post-surgery, best-corrected visual acuity (BCVA) and SMH height exhibited significant improvements (P < 0.01). In eyes with preoperative SMH height < 300 µm and a detectable EZ line, BCVA was significantly improved at as early as 1 month, whereas the remaining eyes exhibited visual improvements only at 3 months. Postoperative BCVA positively correlated with preoperative BCVA (r = 0.86, P < 0.005), and negatively correlated with SMH size (r = 0.69, P < 0.01) and PED height (r = 0.58, P < 0.05) and width (r = 0.67, P < 0.05). Multivariate analyses confirmed preoperative BCVA as the predominant factor associated with postoperative BCVA (β = 1.093, P < 0.05). In conclusion, significant improvements in BCVA and anatomical findings can be achieved with our reported surgical technique. Preoperative OCT findings may influence the duration required for visual improvements.
... Intravitreal t-PA or subretinal t-PA may help liquefy the clot and aid pneumatic displacement. Either vitrectomy can evacuate SMH or t-PA can be injected subretinally to displace SMH using expansile gas 15,16 . ...
... A few studies with small number of patients compared surgical treatment with non-surgical treatment 15,16 . However, most previous studies were conducted with one or two treatment methods rather than three or more [6][7][8][9][10][11][13][14][15][16][17][18][19][20] . ...
Article
Full-text available
The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P < 0.001). Only baseline BCVA was associated with VA gain at 12 months (Odds ratio = 3.53, P < 0.001). This study demonstrated that there was no difference in 12 month visual outcomes among treatments and a better early visual outcome can be expected with anti-VEGF monotherapy.
... Since the 20th century, cardiovascular disease has become a leading cause of death in humans, and its pathogenesis is commonly related with the thromboembolic condition. Currently, thrombolytic therapy is the most effective treatment in managing thromboembolism [1][2][3]. Human tissue-type plasminogen activator (tPA) is a serine protease synthesized and secreted by vascular endothelial cells. As an effective thrombolytic drug, it can efficiently dissolve thrombus [4]. ...
Article
Full-text available
Human tissue-plasminogen activator (tPA) is a thrombolytic drug widely used in the treatment of stroke, pulmonary thrombosis, acute myocardial infarction, and other thrombotic diseases. The double genes cointegrated into the organisms and cells can produce a synergistic effect, which will improve the expression level of the target gene. However, the study of the integration of the GH and tPA genes to improve the expression level of tPA has not yet been reported. In order to elucidate this, we generated monoclonal goat mammary epithelial cell lines with tPA/GH double-gene integration and analyzed the tPA expression level in single- and double-gene integrated cells. We selected the mammary gland-specific expressing vectors BLC14/tPA and BLC14/GH with the β-lactoglobulin gene as a regulatory sequence in our previous research. The tPA and GH genes were electronically cotransfected into goat mammary epithelial cells. Resistant cell lines were screened by G418, and transgenic monoclonal cell lines were confirmed by PCR. The tPA expression was induced by prolactin and detected in the cell induction solution after 48 h by ELISA and Western blotting. We detected the tPA biological activity in vitro by fibrin agarose plate assay (FAPA). The results showed that a total of 207 resistant monoclonal cells were obtained, including 126 cell lines with tPA monogenic integration and 51 cell lines with tPA/GH double-gene integration. The rate of double-gene integration was 24.6% (51/207). A total of 48 cells expressed tPA, of which 25.3% (19/75) cells expressed single gene, and 56.9% (29/51) cells expressed double genes. The concentration of tPA in single-gene-expressing cells was 8.0-64.0 μg/mL, and the tPA level in double-gene-expressing cells was significantly higher (200-7200 μg/mL). In addition, the tPA had a relatively strong in vitro thrombolytic activity determined by FAPA. The results showed that goat mammary epithelial cell lines with tPA/GH gene integration were successfully established by electrotransfection, and the expression level of tPA in double-gene integrated cell lines was significantly increased. This study provided a new way for the preparation of a transgenic goat and other animal with high tPA expression by somatic cell nuclear transfer. The findings also laid a foundation for efficient production of pharmaceutical proteins in transgenic animal mammary gland bioreactors in the future.
... Die Patienten werden dann angewiesen, eine Kopf-vor-Bauch Lagerung einzuhalten, um eine mechanische Verlagerung der subretinalen Blutung durch die Gasblase zu ermöglichen. Zahlreiche Studien konnten zeigen, dass durch diesen Therapieansatz selbst bei prominenten zentralen subretinalen Hämorrhagien und sogar in pädiatrischen Fällen oder bei Makulablutungen nach Trauma eine erfolgreiche Dislokation erreicht werden kann [8][9][10][11][12][17][18][19][20]. Eigene Daten sowie die Ergebnisse anderer Untersucher belegen zudem, dass mit der Kombination von intravitrealer rt-PA-Gabe und Gastamponade selbst bei ausgedehnten Blutungen am hinteren Pol in einem bis zwei Drittel aller Fälle eine deutliche Visusverbesserung bis hin zum Erreichen eines Lesevisus erzielt werden kann [8,10,12,21]. ...
Article
Full-text available
Background Subretinal hemorrhage involving the macula is a typical complication in a variety of retinal diseases, whereby age-related macular degeneration (AMD) is by far the leading cause.MethodA literature search was carried out in PubMed.ResultsNumerous studies have demonstrated the effectiveness of various approaches to the management of submacular hemorrhage, including intravitreal anti-VEGF treatment, pneumatic displacement supported by fibrinolytic agents or surgical drainage.DiscussionThere is currently no consensus regarding evidence-based standard treatment for macular hemorrhage, although there is a trend towards minimally invasive approaches. Regardless of the choice of the primary treatment approach, the time to treatment and an accompanying intravitreal treatment with VEGF inhibitors are decisive for the functional outcome.
Article
Full-text available
Purpose of Review To review management strategies for submacular hemorrhage with a focus on studies from the last five years. Recent Findings Thick submacular hemorrhage is a potentially devastating complication of choroidal neovascularization, trauma, retinal vascular disease, and ophthalmic surgery. Common treatments include intravitreal antiangiogenic therapy, pneumatic displacement, pars plana vitrectomy, intravitreal or subretinal tissue plasminogen activator, subretinal air, and combinations thereof. Recent reports support the safety and efficacy of numerous treatment strategies and have offered improved techniques and instrumentation for subretinal injections. Summary While there are numerous options for the patient with submacular hemorrhage, optimal management remains controversial. Randomized controlled trials are ongoing, and additional study is still needed to refine the treatment paradigm.
Article
Purpose: To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. Methods: This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. Results: Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; β = -0.60). Conclusion: Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.
Article
Full-text available
Purpose: Submacular haemorrhage (SMH) is a cause of severe visual loss in neovascular age-related macular degeneration (nAMD). The incidence is uncertain and furthermore there is no widely used classification system nor agreed best practice. The aim of this national surveillance study was to identify the incidence, presenting features and clinical course of new fovea-involving submacular haemorrhage associated with nAMD. Methods: A questionnaire was sent monthly to every ophthalmic specialist in Scotland over a 12-month period asking them to report all newly presenting patients with acute SMH secondary to nAMD of at least two disc diameters (DDs) in greatest linear diameter. A follow-up questionnaire was sent 6 months after initial presentation. Cases related to other causes were excluded. Results: Twenty-nine cases were reported giving an incidence of 5.4 per million per annum (range 2-15). The mean age was 83 years (range 66-96) and females accounted for 17/29 (59%). Fifteen of the 29 cases (52%) had a past history of AMD, of which 7 had nAMD. Nineteen of the 29 cases (66%) presented within 7 days of onset and the majority had SMH of < 11 DD (20/29, 69%). Treatment options comprised the following: observation (n = 6, 21%), anti-VEGF alone (n = 6, 21%) or vitrectomy with co-application of tissue plasminogen activator (TPA), anti-VEGF and gas (n = 17, 58%). The vitrectomy group experienced the greatest change in vision from logMAR 1.89-1.50 (p = 0.374). Four of 20 (20%) cases with 6 months follow-up suffered a re-bleed at a mean time of 96 days. Conclusions: The incidence, clinical features and course of a consecutive national cohort of patients with SMH secondary to nAMD are presented.
Article
Full-text available
Purpose: To report the results of our sequential intravitreal (IV) tissue plasminogen activator (tPA), pneumatic displacement (PD), and IV anti-vascular endothelial growth factor (VEGF) treatment in patients with neovascular age-related macular degeneration (nAMD)-related submacular hemorrhage (SMH). Methods: A total of 16 eyes of 16 patients with SMH of less than 15 days duration were included in this retrospective pilot study. The tPA was applied on the day of diagnosis, and PD was performed the following day. Patients received 3 consecutive monthly IV injections of ranibizumab starting from 15 days after PD. During the follow-ups, additional ranibizumab treatment was performed if persistent macular or recurrent subretinal or intraretinal fluid hemorrhage was observed. Results: The mean central retinal thickness was 489 ± 92 μm (311-621 μm) at the time of diagnosis, 324 ± 56 μm (209-409 μm) at the first month, 262 ± 48 μm (197-364 μm) at 3 months, 248 ± 40 μm (190-334 μm) at 6 months, and 253 ± 41 μm (192-356 μm) at the last control (p<0.01). The mean best-corrected visual acuity was 2.08 ± 0.79 logMAR (0.7-3.0 logMAR) at baseline, 1.41 ± 0.70 logMAR (0.56-2.50 logMAR) at the first month, 1.21 ± 0.66 logMAR (0.3-2.0 logMAR) at 3 months, 1.14 ± 0.77 logMAR (0.2-2.50 logMAR) at 6 months, and 1.09 ± 0.73 logMAR (0.3-2.50 logMAR) at the last follow-up (p<0.01). Conclusions: Sequential IV tPA, PD, and IV anti-VEGF treatments for SMH in patients with nAMD is effective. However, further studies are needed to establish the best treatment algorithm for SMH in patients with nAMD.
Article
Full-text available
Purpose The purpose of this study was to evaluate the treatment efficacy of vitrectomy combined with subretinal recombinant tissue plasminogen activator (r-tPA) and factors affecting visual improvement in patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (nAMD). Materials and Methods Medical records of 17 consecutive patients diagnosed with SMH secondary to nAMD were retrospectively reviewed. The initial surgical procedure involved a 23-gauge transconjunctival vitrectomy, subretinal r-tPA application through a self-sealing inferior retinotomy, and sulfur hexafluoride gas for tamponade in all patients. The duration, size, and thickness of the hemorrhage and the pre- and post-operative visual acuity (VA) using a Snellen chart were recorded. VA was converted to logMAR for statistical analysis. Results The average duration and size of the SMH were 12.8 ± 18.2 days and 8.6 ± 5.3 disc areas, respectively. The mean follow-up time was 16.9 ± 4.7 months. A statistically significant visual improvement was found when comparing initial VA with postoperative best-corrected VA (BCVA) and final BCVA (Wilcoxon rank test, P ≤ 0.01). There was no significant correlation between the size of the hemorrhage and postoperative BCVA and final BCVA (Spearman's rho test). There was no statistically significant correlation between the initial VA and postoperative BCVA and final BCVA (Spearman's rho test). There was no significant correlation between the duration of hemorrhage and postoperative BCVA and final BCVA (Spearman's rho test). The preoperative thickness of hemorrhage (747.5 ± 30 μm) was not correlated with postoperative BCVA or final BCVA (Pearson's test). Conclusions Vitrectomy combined with subretinal r-tPA injection and gas tamponade is an effective surgical intervention to preserve VA in selected patients with apparent SMH.
Article
Full-text available
Purpose: To assess the incidence of pigment epithelial detachment (PED) in age-related macular degeneration (AMD) with submacular hemorrhage (SMH) and its response to treatment with pars plana vitrectomy (ppV), subretinal co-application of recombinant tissue plasminogen activator (rtPA) and anti-VEGF, and an intravitreal gas tamponade. Methods: Consecutive interventional case series of 132 eyes of 129 patients with neovascular AMD with SMH. All eyes underwent ppV with subretinal co-application of rtPA and bevacizumab followed by a gas tamponade. Postoperatively, two additional intravitreal anti-VEGF injections were applied monthly, followed by intravitreal anti-VEGF injections applied PRN thereafter. PEDs and SMHs were evaluated with SD-OCT pre- and postoperatively. Results: Preoperatively, 88 of 132 (67%) eyes were examined by OCT, and in 81 of these eyes the RPE could be visualised. A PED was found in 74 (91%) eyes, and no PED was found in five (6%) eyes. Median height of preoperative PED was 503 μm (range 150-1242, n = 65) and reduced to 344 (n = 62) and 306 μm (n = 27) after 3 and 12 months respectively. Two eyes showed a pre-existing rip of the RPE. Postoperatively, a rip was documented in 12 of 128 (9%) eyes. Median height of SMH was 762 μm (range 217-1840), median diameter was 4.3 (1.5-15) disc diameter. A complete displacement of the SMH from the fovea was achieved in 112 of 129 (87%) eyes. Overall, median best-corrected logMAR visual acuity (BCVA) improved significantly from preoperative 1.6 (0.5-2.0, n = 132) to 1.0 (0.2-2.0) 3 (n = 132) and 12 months (n = 74) postoperatively. Excluding eyes with pre-existing macular scars (n = 22), BCVA 3 months postoperatively was 0.8. Height of PED or SMH did not correlate with postoperatively BCVA, while size of SMH showed a mild correlation (rho = 0.25, p = 0.005). Conclusion: PpV with subretinal co-application of rtPA and bevacizumab and an intravitreal gas tamponade effectively displaces SMH and improves BCVA. Preoperatively, PED is found in the majority of eyes. Height of PED or SMH did not correlate with postoperatively BCVA. Tears of the RPE occur as frequently as in exudative AMD without SMH.
Article
Full-text available
We describe three cases of submacular hemorrhage that occurred two to four days after anti-VEGF intravitreal injection for occult choroidal neovascularisation in age-related macular degeneration and their management with 25 gauge pars plana vitrectomy with injection of subretinal recombinant tissue plasminogen activator (rTPA) followed by fluid-air exchange and postoperative prone position. Vitrectomy, subretinal rTPA injection and fluid-gas exchange apply as a safe and effective treatment in these cases. Functional results seem to be positive especially if surgical treatment is promptly performed.
Article
Full-text available
Choroidal neovascular membrane (CNVM) is one of the most common causes of submacular hemorrhage (SMH). Conventional treatment involves management of the SMH with pneumatic displacement with or without tissue plasminogen activator (TPA) followed by intravitreal injection of bevacizumab in a second sitting. We decided to assess the efficacy of treating SMH secondary to CNVM with pneumatic displacement using sulphur hexafluoride (SF6) gas and intravitreal bevacizumab. Four patients with SMH secondary to CNVM were included in this study. Intravitreal bevacizumab, 0.05 ml, along with 0.5 ml of SF6 was injected through the pars plana into the vitreous cavity. Postoperative best corrected visual acuity improved in all eyes with complete or partial displacement of SMH out of the foveal area.
Article
Full-text available
The Freiburg Visual Acuity Test (FrACT) has been suggested as a promising test for quantifying the visual acuity (VA) of patients with very low vision, a condition often classified using the semi-quantitative clinical scale "counting fingers" (CF), "hand motion" (HM), "light perception" (LP) and "no light perception". The present study was designed to assess FrACT performance in a sizable number of CF, HM, and LP patients in order to generate a setting for future clinical studies in the low vision range. We examined a total of 41 patients (LP, n = 11; CF, n = 15; HM, n = 15) with various eye diseases (e.g., diabetic retinopathy, ARMD), covering the clinical VA scale from LP to CF. The FrACT optotypes were presented at a distance of 50 cm on a 17-inch LCD monitor with four random orientations. After training, two FrACT measurements (test and retest) were taken, each comprising 30 trials. FrACT measures reproducibly the VA of CF and HM patients. In CF patients, FrACT resulted in a mean logMAR = 1.98 +/- 0.24 (corresponding to a decimal VA of 0.010), for HM in a mean logMAR = 2.28 +/- 0.15 (corresponding to a decimal VA of 0.0052). In all LP patients the FrACT values were close to what would be obtained by random guessing. The mean test-retest 95% confidence interval was 0.21 logMAR for CF patients and 0.31 logMAR for HM respectively. Test-retest variability declined from 24 to 30 trials, showing that at least 30 trials are necessary. FrACT can reproducibly quantify VA in the CF and HM range. We observed a floor effect for LP, and it was not quantifiable further. Quantitative VA measures are thus obtainable in the very low-vision range using FrACT.
Article
Background and objective: The objective of this study was to compare visual acuity outcomes between the following procedures used to treat submacular hemorrhages: pneumatic displacement followed by intravitreal tissue plasminogen activator (tPA) if needed (pneumatic ± tPA) and pars plana vitrectomy (PPV) with subretinal tPA (PPV + tPA). Patients and methods: This is a retrospective chart review of submacular hemorrhages treated with either pneumatic ± tPA or PPV + tPA. Results: Eighteen patients had pneumatic ± tPA, and 14 patients had PPV + tPA. The percentage of patients achieving three lines or greater of vision improvement 1 year postoperatively was 46% and 18% in these groups, respectively (P = .194). Conclusion: The difference in visual acuity was not statistically significant; however, the lack of a statistical difference is important as pneumatic ± tPA is a less-invasive, less costly procedure that can be done in a clinical setting. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:26-32.].
Article
PurposeAcute submacular haemorrhage secondary to wet age-related macular degeneration (AMD) has a poor prognosis for which there is currently no 'gold standard' treatment. We evaluated the efficacy of early treatment using intravitreal triple therapy of tissue plasminogen activator (tPA), expansile gas, and an anti-VEGF agent.Methods This retrospective case series included eight patients presenting with acute submacular haemorrhage involving the fovea. All patients received treatment with 50 μg (0.05 ml) tPA, 0.3 ml 100% perfluoropropane (C3F8), and an anti-VEGF agent (0.05 mg Ranibizumab or 1.25 mg Bevacizumab in 0.05 ml) administered via intravitreal injection. An anterior chamber paracentesis post injection or vitreous tap was performed before injection to prevent retinal vascular occlusion secondary to raised intra-ocular pressure. Outcomes assessed were visual acuity, change in macular morphology, and complications.ResultsPatients presented promptly with delay between symptom onset and clinic review being 1.9±0.6 days (mean±SD). Treatment was delivered quickly with interval from presentation to treatment being 1.1±1.2 days. Symptom onset to treatment was 3.0±1.0 days. Subfoveal haemorrhage was effectively displaced in all patients. LogMAR visual acuity improved from 1.67±0.47 at presentation to 0.63±0.33 at final follow-up (P<0.0001), a mean of 7.9±4.8 months after treatment. Central retinal thickness improved from 658.1±174.2 μm at presentation to 316.6±142.4 μm at final follow-up (P=0.0028).Conclusions Early treatment of submacular haemorrhage using intravitreal tPA, C3F8, and anti-VEGF was effective in significantly improving visual acuity in this series of patients who presented soon after symptom onset. Treatment was well tolerated in this group of elderly and potentially frail patients.Eye advance online publication, 15 April 2016; doi:10.1038/eye.2016.67.
Article
Objective To assess the efficacy and complications of intravitreal injection of perfluoropropane gas for displacement of subretinal hemorrhage (SRH), without the use of tissue plasminogen activator.Patients and Methods Pure perfluoropropane gas (0.4-0.5 mL) was injected into the vitreous cavity in 5 patients with SRH involving the fovea because of age-related macular degeneration (4 eyes) or ruptured retinal arterial macroaneurysm (1 eye). The patients were instructed to maintain a prone position.Results Visual acuity ranged from 20/300 to 20/2000 before gas injection. On the day after gas injection, SRH was dramatically displaced in 3 eyes and slightly displaced with a reduction in the thickness of subfoveal hemorrhage in the remaining 2 eyes. Final visual acuity improved in all cases, ranging from 20/15 to 20/220. Three eyes had a final visual acuity of 20/50 or better. Vitreous hemorrhage caused by migration of SRH into the vitreous cavity and retinal detachment each occurred in 1 eye, and both complications were successfully treated by vitrectomy.Conclusions Gas injected into the vitreous cavity can displace SRH without the use of tissue plasminogen activator in some cases. Visual acuity after gas injection may be improved, making this treatment an alternative to evacuation of SRH with vitrectomy.
Article
• Subretinal blood within the macula may cause visual loss in a number of macular diseases. The clinical and histopathologic effects of experimental subretinal hemorrhage were evaluated in the cat. Subretinal hemorrhages were produced by creating a focal neurosensory retinal detachment with micropipette techniques, then inserting a needle tip transsclerally to allow choroidal blood to fill the bleb. Experimental lesions were examined clinically and with light and electron microscopy during a 14-day postoperative period. Initial observations included clot organization with retraction of fibrin strands. In six of nine clots more than 1 hour old, fibrin was associated with tearing of sheets of photoreceptor inner and outer segments. Later degeneration progressed to involve all retinal layers overlying the densest areas of fibrin in the clots. Hemorrhages into subretinal blebs containing tissue plasminogen activator did not form fibrin strands or cause photoreceptor tearing. These findings highlight the potential for improved retinal survival if organized subretinal clot can be eliminated soon after formation.
Article
To evaluate the outcome of pars plana vitrectomy, subretinal tissue plasminogen activator (t-PA) infusion and intraocular gas tamponade with and without post surgical anti-vascular endothelial growth factor (VEGF) injection for thick submacular hemorrhage due to exudative age-related macular degeneration (AMD) DESIGN: Retrospective, comparative, interventional case series. Setting: Two retina referral centers. Patient population: 101 eyes of 101 patients with neovascular AMD with thick submacular hemorrhage who underwent surgical displacement of the hemorrhage with or without post-operative anti-VEGF injections. Main outcome measures included degree of blood displacement, best and final postoperative visual acuity (VA), and adverse events. Snellen acuity was converted to logMAR for statistical analysis. All patients were followed for a minimum of 3 months (mean 15.3 months, range 3 to 70 months). In 83 (82%) of 101 eyes, the procedure resulted in complete hemorrhage displacement from the fovea. Mean pre-operative VA was 20/2255 (2.05 logMAR). The acuity significantly improved to 20/893 (1.65 logMAR) at month 1 (p<0.001) at month 1, 20/678 (1.53 logMAR) at month 3 (p<0.001), and 20/1150 (1.76 logMAR) at month 12 (p=0.002). Best post-operative visual acuity improved by at least one line in 83 (82%) of 101 eyes and 19.6% of eyes gained 3 lines or more at month 3. The visual acuity of the group of eyes that received post-operative anti-VEGF injection (n=39) showed greater visual acuity improvement 6 months postoperatively compared to the group of eyes that did not receive post-operative anti-VEGF. Postoperative complications included vitreous hemorrhage in 2 eyes, rhegmatogenous retinal detachment in 4 eyes, and recurrent thick subretinal hemorrhage in 6 eyes. Vitrectomy with subretinal t-PA injection and gas tamponade was found to be relatively effective for displacement of thick submacular hemorrhage with a significant improvement in visual acuity. There is a loss of acuity over time; the addition of post-operative anti-VEGF therapy may help maintain the visual acuity gains.
Article
In order to simulate the hemorrhagic detachment stage of disciform macular degeneration, we injected fresh autologous blood into the subretinal space of albino rabbits and studied these hemorrhages clinically with the ophthalmoscope and by light and electron microscopy. One hour after injection, retinal changes were minimal and limited to occasional photoreceptor edema. At one day, there was marked damage of the photoreceptor cells characterized by edema and disintegration of the photoreceptors and pyknosis of the outer nuclear layer. Some photoreceptors had been pulled off the retina by contraction or movement of the blood clot, or both. By seven days, the photoreceptor cells were almost absent. Subretinal hemorrhage in rabbits led to irreversible retinal destruction within 24 hours. We think that the mechanism of the destruction of the overlying retina consists of a combination of a diffusion barrier by the clot, mechanical damage to the outer segments by contraction of the clot, and iron toxicity.
Article
Subretinal blood within the macula may cause visual loss in a number of macular diseases. The clinical and histopathologic effects of experimental subretinal hemorrhage were evaluated in the cat. Subretinal hemorrhages were produced by creating a focal neurosensory retinal detachment with micropipette techniques, then inserting a needle tip transsclerally to allow choroidal blood to fill the bleb. Experimental lesions were examined clinically and with light and electron microscopy during a 14-day postoperative period. Initial observations included clot organization with retraction of fibrin strands. In six of nine clots more than 1 hour old, fibrin was associated with tearing of sheets of photoreceptor inner and outer segments. Later degeneration progressed to involve all retinal layers overlying the densest areas of fibrin in the clots. Hemorrhages into subretinal blebs containing tissue plasminogen activator did not form fibrin strands or cause photoreceptor tearing. These findings highlight the potential for improved retinal survival if organized subretinal clot can be eliminated soon after formation.
Article
Subretinal hemorrhage can arise from the retinal and/or choroidal circulation. Significant subretinal hemorrhage occurs in several conditions, but most commonly is associated with age-related macular degeneration, presumed ocular histoplasmosis, high myopia, retinal arterial macroaneurysm, and trauma. Released toxins, outer retinal shear forces, and a diffusion barrier created by subretinal hemorrhage all contribute to photoreceptor damage and visual loss. The use of tissue plasminogen activator and improvements in surgical instrumentation have facilitated surgical drainage and have made it a useful option in the management of selected cases. Mechanisms of subretinal hemorrhage formation, underlying etiologies, diagnostic evaluation, and the histopathology of damage are summarized. Published surgical series are reviewed and surgical advances are summarized. The value of surgically removing subretinal hemorrhages to improve visual outcome remains unestablished, because definitive studies have not been performed. Guidelines for selecting candidates for surgical intervention are proposed.
Article
To assess the efficacy and complications of intravitreal injection of perfluoropropane gas for displacement of subretinal hemorrhage (SRH), without the use of tissue plasminogen activator. Pure perfluoropropane gas (0.4-0.5 mL) was injected into the vitreous cavity in 5 patients with SRH involving the fovea because of age-related macular degeneration (4 eyes) or ruptured retinal arterial macroaneurysm (1 eye). The patients were instructed to maintain a prone position. Visual acuity ranged from 20/300 to 20/2000 before gas injection. On the day after gas injection, SRH was dramatically displaced in 3 eyes and slightly displaced with a reduction in the thickness of subfoveal hemorrhage in the remaining 2 eyes. Final visual acuity improved in all cases, ranging from 20/15 to 20/220. Three eyes had a final visual acuity of 20/50 or better. Vitreous hemorrhage caused by migration of SRH into the vitreous cavity and retinal detachment each occurred in 1 eye, and both complications were successfully treated by vitrectomy. Gas injected into the vitreous cavity can displace SRH without the use of tissue plasminogen activator in some cases. Visual acuity after gas injection may be improved, making this treatment an alternative to evacuation of SRH with vitrectomy.
Article
To investigate the efficacy and safety of treating thick submacular hemorrhages with intravitreous tissue plasminogen activator (tPA) and pneumatic displacement. Retrospective, noncomparative case series. From 5 participating centers, 15 eligible patients had acute (<3 weeks) thick subretinal hemorrhage involving the center of the macula in eyes with pre-existing good visual acuity. Hemorrhages were secondary to age-related macular degeneration in 13 eyes and macroaneurysm and trauma in 1 eye each. The authors reviewed the medical records of 15 consecutive patients who received intravitreous injection of commercial tPA solution (25-100 microg in 0.1-0.2 ml) and expansile gas (0.3-0.4 ml of perfluoropropane or sulfur hexafluoride) for thrombolysis and displacement of submacular hemorrhage. After surgery, patients maintained prone positioning for 1 to 5 days (typically, 24 hours). Degree of blood displacement from under the fovea, best postoperative visual acuity, final postoperative visual acuity, and surgical complications. In 15 (100%) of 15 eyes, the procedure resulted in complete displacement of thick submacular hemorrhage out of the foveal area. Best postprocedure visual acuity improved by 2 lines or greater in 14 (93%) of 15 eyes. After a mean follow-up of 10.5 months (range, 4-19 months), final visual acuity improved by 2 lines or greater in 10 (67%) of 15 eyes and measured 20/80 or better in 6 (40%) of 15 eyes. Complications included breakthrough vitreous hemorrhage in three eyes and endophthalmitis in one eye. Four eyes developed recurrent hemorrhage 1 to 3 months after treatment, three of which were retreated with the same procedure. Intravitreous injection of tPA and gas followed by brief prone positioning is effective in displacing thick submacular blood and facilitating visual improvement in most patients. The rate of serious complications appears low. Final visual outcomes are limited by progression of the underlying macular disease in many patients.
Incidence of submacular haemorrhage ( SMH ) in Scotland : a Scottish Ophthalmic Surveillance Unit ( SOSU ) study. Eye. Epub ahead of print
  • A A David
  • H S David
  • Y David
David AA, David HS, David Y, et al. Incidence of submacular haemorrhage ( SMH ) in Scotland : a Scottish Ophthalmic Surveillance Unit ( SOSU ) study. Eye. Epub ahead of print 2018. DOI: 10.1038/s41433-018-0239-4.