Intravitreal Tissue Plasminogen Activator Research Articles

Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration

Evidence is limited to support therapies to treat submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) as an adjunct to anti-vascular endothelial growth factor therapy (anti-VEGF). To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity or promotes resolution of SMH secondary to neovascular AMD in eyes treated with ranibizumab. This was a double-masked, sham-controlled, factorial randomized clinical trial and feasibility study that recruited participants from June 2014 to March 2019, with 12 months' follow-up. Included in the trial were patients from 4 UK vitreoretinal units who had fovea-involving SMH of at least 1 disc area secondary to neovascular AMD and were evaluated within 14 days of onset. Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to 1 of 4 intravitreal treatments: sham injection, perfluoropropane (C3F8), TPA, or combined C3F8 and TPA (C3F8 + TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. Outcome assessors were masked to intervention assignment. Best-corrected visual acuity (BCVA) at month 3. Fifty-three of 56 participants (95%; mean [SD] age, 81.5 [8.1] years; 33 female [59%]) reached the primary end point. Study eyes were randomized to the following intravitreal treatments: sham injection (n = 23), C3F8 (n = 11), TPA (n = 11), or C3F8 + TPA (n = 11). On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR BCVA than those not receiving TPA: 0.66 vs 0.98 (μd = -0.32; 95% CI, -0.58 to -0.07; P = .02). There was no statistically significant difference comparing groups that did vs did not receive C3F8: 0.80 vs 0.90 (μd = -0.11; 95% CI, -0.37 to 0.16; P = .43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P = .03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the groups: monotherapy control, 0.99; C3F8, 0.97 (vs control μd = -0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control μd = -0.29; 95% CI, -0.79 to 0.21); combined C3F8 and TPA, 0.71 (vs control μd = -0.36; 95% CI, -0.82 to 0.11); P = .11. No safety differences were identified across the treatment groups. Results of this randomized clinical trial suggest that TPA may increase the chance of visual acuity gain when added to ranibizumab therapy for neovascular AMD in eyes with SMH, warranting consideration of additional clinical trials. ClinicalTrials.gov Identifier: NCT01835067.

Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration

To compare the efficacy and the safety of submacular hemorrhage (SMH) management with either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD), with tissue plasminogen activator (TPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. Randomized, open-label, multicenter superiority study. Ninety patients with neovascular age-related macular degeneration (nAMD) aged ≥50 years, with recent SMH (≤14 days) greater than 2 optic disk areas and predominantly overlying the retinal pigment epithelium. Patients were randomly assigned to surgery (PPV, subretinal TPA [max 0.5 ml/50 μg], and 20% sulfahexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal TPA [50 μg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at Month 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at Month 3. The secondary endpoints were mean VA change at Month 6, National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) composite score value at Month 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. Of the 90 patients randomized, 78 (86.7%) completed the 3-month efficacy endpoint visit. The mean±SD age was 83.3±8.2 years, and 66.3% were female. The mean duration of symptoms before treatment was 7.5±4.4 days. The mean VA change from baseline to Month 3 in the surgery group (+16.8 letters, [95% CI, 8.7; 24.9]) was not significantly superior to the PD group (+16.4 letters, [95% CI, 7.1;25.7]; adjusted difference β, -1.9 [95% CI, -14.9;11.0], P = 0.767). Both groups achieved similar secondary outcomes at Month 6. No unexpected ocular safety concerns were observed in either group. Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared to PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of visual acuity without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments.

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.

Rhegmatogenous retinal detachment after injection of tissue plasminogen activator and gas for submacular hemorrhage secondary to age-related macular degeneration.

To describe the rate, clinical characteristics and outcomes of rhegmatogenous retinal detachment (RRD) after injection of tissue plasminogen activator (TPA) and gas for submacular hemorrhage (SMH) displacement. Retrospective analysis of consecutive cases developing RRD after TPA injection and gas for SMH displacement. The rate of RRD was calculated and a description of RRD clinical characteristics was carried out. Anatomic and visual outcomes after RRD repair were analyzed. Ninety eyes of 90 patients were analyzed. TPA was given intravitreally in 53 eyes (59%) and subretinally in 37 eyes (41%). RRD occurred in 6/90 eyes (7%). Of these, one had intravitreal TPA and five had vitrectomy with subretinal TPA (p=0.04). The mean age was 75 [64-93] years. The median time of RRD occurrence was 42 [1-134] days. All cases had macular involvement. Two cases had PVR at presentation. Vitrectomy was performed in all cases and silicone oil used in five, all of which resulted in permanent silicone oil retention. One case (17%) achieved primary single surgery success. The median final visual acuity was 1.8 logMAR (20/1260 Snellen). The RRD rate after SMH displacement was 7% in our cases series. RRD occurred more commonly after vitrectomy with sub-retinal TPA injection. The visual and anatomical outcomes were poor, with a high rate of retained silicone oil and recurrent RRD.

Intravitreal recombinant tPA before vitrectomy for diabetic tractional retinal detachment: A randomized controlled trial.

To investigate the effect of intravitreal recombinant tissue plasminogen activator (rt-PA) injection before vitrectomy on surgical facility and outcome in diabetic tractional retinal detachments (TRD). Prospective, randomized, interventional clinical trial. A total of 38 eyes with diabetic TRD were candidates for vitrectomy. Patients were randomized 1:1 to receive intravitreal rt-PA, five to seven days before vitrectomy or no injection. Intraoperative surgical facility and anatomic success at month 3 after surgery were assessed. Mean patient age was 54.2 ± 9.4 years. There was no statistically significant difference between rt-PA and no injection groups with regard to anatomic success (89% versus 95%, respectively, P = 0.547) and best corrected visual acuity at 3 months (2.0 versus 2.1 logMAR, respectively, P = 0.840). However, surgical facility score was statistically significantly lower in rt-PA injection group compared to no injection group (4.1 ± 1.7, 5.8 ± 2.0, respectively, P = 0.007). Vitrectomy for TRD was easier after preoperative rt-PA injection, without affecting the anatomic and visual outcomes.

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.

The effect of intravitreal recombinant tissue plasminogen activator injection on diabetic tractional fibrovascular membranes: Proposed criteria using optical coherence tomography

To evaluate the effect of intravitreal recombinant tissue plasminogen activator (tPA) on diabetic tractional fibrovascular membranes (FVM) using proposed optical coherence tomography (OCT) criteria. This prospective, interventional case series enrolled eyes with tractional retinal detachment who were candidates for pars plana vitrectomy. OCT images were obtained to evaluate the border of the attached-detached retina and overlying FVP at baseline and 1 week post-intravitreal tPA injection using the follow-up scan acquisition protocol. Two independent graders assessed retinal detachment (RD) height, FVM height, and retinal thickness at the site of membrane attachment. Thirteen eyes from 13 individuals were included. Assessment of RD height, FVM height, and retinal thickness at membrane attachment point were feasible at both visits in 10/13 (77%), 10/13 (77%), and 8/13 (62%) of eyes, respectively. There was excellent agreement between the two graders for all measurements (all ICC > 0.94). Release of the retina-membrane attachment point was not observed in any eyes. No statistically significant change was found in any of the measured parameters. Excellent agreement was achieved between the graders for quantitative assessment of diabetic FVM using our proposed OCT criteria. We did not observe a significant change in the FVM measurements, 1-week after intravitreal tPA injection.

The effect of initial intravitreal tissue plasminogen activator and gas injection on vision improvement in patients with submacular haemorrhage associated with age-related macular degeneration

PurposeTo compare visual improvements between initial intravitreal t-PA with gas injection before anti-vascular endothelial growth factor (VEGF) and anti-VEGF injection monotherapy for submacular haemorrhage (SMH) associated with age-related macular degeneration (AMD).MethodsWe retrospectively reviewed medical records of naive patients treated with intravitreal t-PA with gas injection before anti-VEGF (Group 1) or only with intravitreal anti-VEGF injection (Group 2) for SMH [disc area (DA) ≥ 2] associated with AMD from two institutions. Both groups received 3 monthly loads of anti-VEGF injections followed by injections as needed for AMD treatment. Changes in best-corrected visual acuity (BCVA, logMAR) between the initial visit and after 6 months of treatment were compared between two groups.ResultsA total of 82 patients were enroled. Of these, 32 patients and 50 patients were grouped in Groups 1 and 2, respectively. The mean change in BCVA over 6 months for Group 1 was −0.52 ± 0.88, which was significantly larger (p = 0.044) than the mean change for Group 2 (−0.15 ± 0.58). We compared visual improvements between the two groups based on the following SMH size categories: ≤5, >5, and ≤15, and >15 DA. When the SMH size was ≤5, or >5 and ≤15 DA, the mean change in BCVA was larger for Group 1 than for Group 2, but this difference was not significant. When SMH size was >15 DA, Group 1 patients exhibited a mean visual improvement of −0.79 ± 0.80, which was significantly greater (p = 0.029) than that of Group 2 (−0.06 ± 0.67).ConclusionsPatients that were primarily treated for SMH associated with AMD using t-PA and gas injection (followed by anti-VEGF injection) exhibited better visual improvement than those treated with anti-VEGF monotherapy, especially in patients exhibiting larger SMH sizes (>15 DA) at the initial visit.

Risk factors for breakthrough vitreous hemorrhage after intravitreal tissue plasminogen activator and gas injection for submacular hemorrhage associated with age related macular degeneration.

PurposeWe investigated risk factors for breakthrough vitreous hemorrhage (VH) after an intravitreal tissue plasminogen activator (tPA) and gas injection in patients with submacular hemorrhage (SMH) associated with age-related macular degeneration (AMD).MethodsThe medical records of patients diagnosed with SMH associated with AMD who received an intravitreal tPA (50 μg/0.05 mL) and perfluoropropane gas (0.3 mL) injection were reviewed retrospectively. We analyzed the associations of breakthrough VH with age, sex, best-corrected visual acuity, intraocular pressure, AMD subtype, accompanying sub-retinal pigment epithelium (RPE) hemorrhage, history of cataract surgery, history of hypertension and diabetes mellitus, history of drinking and smoking, and history of antiplatelet or anticoagulant medication. We also examined the relationships between various parameters, including the area ratio of the SMH to the optic disc (AHD) and the height of the SMH obtained from optical coherence tomography.ResultsIn total, 52 eyes from 52 patients were enrolled in this study; 16 eyes (30%) showed breakthrough VH. The proportions of patients with a current smoking history were 75.0% in the VH group and 22.2% in the non-VH group (p = 0.010). Other factors did not differ significantly between the two groups. The proportion of cases with accompanying sub-RPE hemorrhage was 50.0% and 58.3% in the VH and non-VH groups, respectively (p = 0.763). The AHD (p = 0.001) and SMH height (p < 0.001) were significantly greater in the VH group. In a receiver operating characteristic curve analysis, the cut-off values of AHD and SMH height were 20.1 and 1208 μm, respectively. According to logistic regression analysis, when the AHD and SMH height were greater than the individual cut-off values, the odds ratio of VH increased by 10.286 fold (95% confidence interval [CI], 2.452–43.148; p = 0.001) and 75.400 fold (95% CI, 7.991–711.441; p < 0.001), respectively, with respect to their respective reference groups (less than the cut-off value). Among the significant factors associated with VH occurrence, including current smoking, AHD, and SMH height, only current smoking and SMH height were found to be significant in multiple regression analysis (p = 0.040, 0.016).ConclusionsThe incidence of breakthrough VH was significantly higher in those with current smoking status and for SMH with a larger AHD and greater height. The height of the SMH was more predictable of the possibility of VH than AHD.

Comparison between different techniques for treatment of submacular haemorrhage due to Age-Related Macular Degeneration.

To compare the outcome of vitrectomy, subretinal tissue plasminogen activator (TPA), and gas with and without subretinal air versus Intravitreal TPA and gas in the treatment of submacular haemorrhage (SMH) due to Neovascular age related macular degeneration. We analysed the notes of 29 cases presented with SMH in the period between 01/2016 and 09/2018 at James Cook University Hospital. Presenting visual acuity (BCVA), size and location of SMH, Procedure done, final BCVA at 6 months and any surgical complications were recorded. 11 Cases (Group 1) received intravitreal TPA (50 µg in 0.1 ML), 0.3 ml of pure sulfur hexafluoride (SF6). 18 cases (Group 2) received 23 G Pars Plana vitrectomy, Subretinal TPA injection (25 µg in 0.1 ml), and 20% SF6 gas filling. Group 2 was further divided into 2A (10 patients) who received only subretinal TPA and group 2B (8 patients) who received additional 0.1 ml subretinal air. The mean BCVA at presentation was 0.0068 in group 1 and 0.0067 in group 2 (p = 0.8734). The mean postoperative BCVA at 6 months was 0.31 in group 1 and 0.58 in group 2 (p = 0.0015). Subgroup analysis of group 2 didn't show statistically significant difference in outcome when adding subretinal air to the vitrectomy procedure (p = 0.7009). Vitrectomy, gas and subretinal TPA has more successful displacement rate and better visual outcome than Intravitreal TPA & Gas alone in treating SMH involving the fovea in age-related macular degeneration. Additional subretinal air doesn't seem to improve the outcome in cases having vitrectomy.

Combined Administration of Preoperative Intravitreal and Intraoperative Subretinal Recombinant Tissue Plasminogen Activator in Acute Hemorrhagic Age-related Macular Degeneration.

PurposeTo evaluate the efficacy of combining pre-operative intravitreal administration of recombinant tissue plasminogen activator (rTPA) followed by 23G pars plana vitrectomy with the subretinal administration of rTPA in the management of acute submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD).MethodsThis is a single-center case series report that included 14 patients with SMH secondary to neovascular AMD. All of them received preoperative intravitreal injection of 0.05 ml (50 µg) rTPA, followed on the next day by 23G pars plana vitrectomy with subretinal 0.1 ml (10 µg) rTPA administration and air tamponade.ResultsThere was a significant (p=0.01) overall improvement in the visual acuity post-treatment (from 1.4±0.5 log MAR to 0.9±0.4). The mean overall change in the visual acuity post-treatment was 0.5±0.3 log MAR (mean % change=31.7±15.1). There was a significant (p=0.03) overall reduction in the central macular thickness post-treatment (896±608.1 µm to 497.2±196.0 µm). The mean overall change in the central macular thickness post-treatment was 398.8±458.1 µm (mean % change=38.1±18.1).ConclusionCombined treatment of 24 hours of preoperative administration of intravitreal rTPA followed the next day by vitrectomy and the administration of subretinal rTPA with air tamponade appeared to be effective as a prompt intervention in managing acute SMH secondary to neovascular AMD. However, similar studies with larger sample size and a control comparative group are warranted to further confirm these findings.

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

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. 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. 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%. 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.

Long-term outcomes of intravitreous bevacizumab or tissue plasminogen activator or vitrectomy for macular edema due to branch retinal vein occlusion.

PurposeThe purpose of this study was to determine the long-term outcomes of intravitreal bevacizumab (IVB) or intravitreal tissue plasminogen activator (tPA) or vitrectomy for macular edema associated with a branch retinal vein occlusion (BRVO).MethodsThis was a retrospective, interventional case series. Forty-one patients received a single 1.25 mg of IVB injection and followed by pro re nata protocol, 71 patients received a single intravitreal tPA, and 116 patients underwent phacovitrectomy with intraocular lens implantation.ResultsThe baseline characteristics and follow-up periods were not significantly different among the three groups. The mean follow-up period was 55.5 months with a range of 12–160 months. Sixteen patients (39.0%) in the IVB group, 24 patients (33.8%) in the tPA group, and two patients (1.7%) in the vitrectomy group underwent additional surgeries during the follow-up period. The best-corrected visual acuity (BCVA) significantly improved in all groups at 1 year after the initial treatment (all, P<0.0001) and at the final visit (all, P<0.0001). The differences in the BCVA between the three groups were not significant at all times after the initial treatment.ConclusionThe three groups led to similar long-term good visual outcomes. However, additional surgeries were performed in more than 30% of patients in the IVB and tPA groups.

Sequential tissue plasminogen activator, pneumatic displacement, and anti-VEGF treatment for submacular hemorrhage.

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). 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. 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). 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.

Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study

Purpose: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. Methods: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. Results: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. Conclusions: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.

Intravitreal Versus Subretinal Tissue Plasminogen Activator Injection for Submacular Hemorrhage.

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). This is a retrospective chart review of submacular hemorrhages treated with either pneumatic ± tPA or PPV + tPA. 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). 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.].

Early treatment of acute submacular haemorrhage secondary to wet AMD using intravitreal tissue plasminogen activator, C3F8, and an anti-VEGF agent.

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.MethodsThis 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).ConclusionsEarly 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.

Intravitreal Tissue Plasminogen Activator, Ranibizumab, and Gas Injection for Submacular Hemorrhage in Polypoidal Choroidal Vasculopathy

To investigate the efficacy of intravitreal injection of recombinant tissue plasminogen activator (rt-PA), ranibizumab, and gas without vitrectomy for submacular hemorrhage. Prospective, interventional, consecutive case series. Twenty consecutive patients (20 eyes) with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). Ranibizumab, rt-PA (25 μg/0.05 ml), and 100% perfluoropropane (0.3 ml) were injected intravitreally, followed by 2-day prone positioning. The primary outcome measure was best-corrected visual acuity (BCVA) 6 months after treatment. Secondary outcome measures included central retinal thickness (CRT), central pigment epithelial detachment (PED) thickness, central ellipsoid zone, recurrence rate, and complications. Underlying disease was exudative AMD in 1 eye and PCV in 19 eyes. Submacular hemorrhage ranged in size from 2 to 31 disc diameters. Complete displacement of submacular hemorrhage was achieved in 17 eyes (85%), and partial displacement was achieved in 3 eyes (15%). Snellen BCVA improved from 20/139 before treatment to 20/65 at 6 months (P= 0.0061). Mean change in Early Treatment Diabetic Retinopathy Study score from baseline was+13 letters (P= 0.0040). Mean CRT decreased from 599 μm before treatment to 208 μm at 6 months (P < 0.0001), and central PED thickness decreased from 188 to 88 μm (P= 0.0140). Three eyes developed vitreous hemorrhage, and 1 eye developed retinal detachment; all were treated surgically, and Snellen BCVA improved at 6 months (P= 0.0012). Recurrence was observed in 10 eyes (50%) within 6 months, but visual acuity was preserved with intravitreal injection of anti-vascular endothelial growth factor (VEGF) pro re nata (PRN). The factors that affect BCVA at 6 months after treatment were pre- and posttreatment central ellipsoid zone (P= 0.0366 and P= 0.0424), pretreatment BCVA (P= 0.0015), and pre- and posttreatment central PED thickness (P= 0.0046, P= 0.0021). Subretinal hemorrhage treatment by intravitreal injection of rt-PA, ranibizumab, and gas is useful to achieve hemorrhage displacement and lesion improvement. To preserve visual acuity, early detection of posttreatment recurrence and intravitreal anti-VEGF injection PRN are necessary.

Intravitreal tPA Injection and Pneumatic Displacement for Submacular Hemorrhage in a 10-Year-Old Child.

Background. Submacular hemorrhage can occur after blunt trauma to the eye. Intravitreal tissue plasminogen activator (tPA) and gas injection are often used for treatment and are effective for submacular hemorrhage caused by age-related macular degeneration. This report describes the clinical outcome in a child with submacular hemorrhage caused by traumatic choroidal rupture who underwent successful intravitreal tPA injection and pneumatic displacement. Case Presentation. A 10-year-old boy developed sudden decrease of vision and a central scotoma in his right eye after trauma. Submacular hemorrhage was found in the eye. Visual acuity was 20/70 OD. Tissue plasminogen activator (12.5 μg in 0.05 mL) and 0.3 mL of pure sulfur hexafluoride were injected into the vitreous cavity under general anesthesia. After surgery, the patient was instructed to maintain a prone position. Displacement of the submacular hemorrhage from the fovea revealed a choroidal rupture, presumed to be the cause of the hemorrhage. After 4 months of follow-up, visual acuity was restored and final visual acuity is 20/16. Conclusion. Intravitreal tPA and gas injection can be an effective treatment for children with submacular hemorrhage.