Search

Unilateral retinal hemorrhage in infants can be caused by vitamin K deficiency. The case described here with fatal outcome presents the medical history of a 2-month-old infant with vitamin K deficiency bleeding caused by the refusal of vitamin K prophylaxis by the parents. Ocular signs were unilateral intraretinal hemorrhage with Roth spots and preretinal hemorrhage over the complete back of the eye. The case demonstrates the importance of vitamin K prophylaxis for newborns.

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.

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.

Background/aims: Subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and vascular endothelial growth factor (VEGF)-antagonists is a new treatment option for age-related macular degeneration complicated by submacular haemorrhage. Here, we investigate the compatibility of rtPA and aflibercept or ranibizumab in vitro because intraoperatively, rtPA or rtPA-induced plasmin may cleave aflibercept or ranibizumab., Methods: Aflibercept and ranibizumab, respectively, were incubated with rtPA or plasmin, separated in gel electrophoresis and stained with Coomassie or silver. The antiangiogenic activity of the VEGF-antagonists was quantified by VEGF-ELISA after incubation with the supernatant of primary porcine retinal pigment epithelium cell cultures., Results: In electrophoresis, ranibizumab displayed no additional fragments when it was coapplied with rtPA or plasmin. Its VEGF-inhibiting efficacy remained unchanged in coapplication with rtPA with or without blood, or plasmin. rtPA did not cleave or functionally compromise aflibercept. When aflibercept was coapplied with plasmin, electrophoresis displayed additional bands in Coomassie (30 kDa, 27 kDa, 19 kDa, 15 kDa) and silver staining (31 kDa, 26 kDa, 21 kDa, 19 kDa, 15 kDa). While at a clinical dosage (800 µg/mL) VEGF was inhibited by aflibercept when coapplied with plasmin, at borderline concentrations (400 ng/mL) VEGF-binding ability of aflibercept was abolished., Conclusions: Ranibizumab is not cleaved or functionally compromised by rtPA or plasmin. Aflibercept is cleaved and its VEGF-binding ability is reduced when coapplied with plasmin. In clinical practice, rtPA and ranibizumab can be coapplied as a treatment for neovascular age-related macular degeneration with submacular haemorrhage while the antiangiogenic activity of aflibercept may be compromised when coapplied with rtPA in the presence of plasmin., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate the compatibility of recombinant tissue plasminogen activator (rtPA) and bevacizumab in vitro because during surgery, rtPA or rtPA-induced plasmin may cleave and inactivate bevacizumab., Methods: To simulate the intraoperative range of mixing ratios of rtPA, bevacizumab, and subretinal blood, we calculated the volumes of 12 submacular hemorrhages (SHs) with a spherical cap formula using measurements derived from fundus photographs and spectral-domain optical coherence tomographic images. Bevacizumab was incubated with rtPA or plasmin before gel electrophoresis with Coomassie blue and silver staining. The anti-angiogenetic activity of bevacizumab in the presence of rtPA with or without clotted human blood or of plasmin was quantified by vascular endothelial growth factor–enzyme-linked immunosorbent assay after incubation with the supernatant of porcine retinal pigment epithelium cell cultures., Results: The mean (SD) volume of SH was 28.6 (24.7) mm3 (range, 6.2-94.6 mm3). In sodium dodecyl sulfate–polyacrylamid electrophoresis with Coomassie blue or silver staining, bevacizumab displayed characteristic patterns of protein bands. No additional fragments were detected in co-application of bevacizumab with either rtPA or plasmin. The anti-angiogenetic activity of bevacizumab remained unchanged in co-application with rtPA with or without blood or plasmin., Conclusions: We demonstrated the absence of cleavage or functional inactivation of bevacizumab by rtPA in an in-vitro model of their intraoperative co-application as a treatment of SH., Clinical Relevance: In clinical practice, rtPA and bevacizumab can be co-applied as a treatment for neovascular age-related macular degeneration with SH to simultaneously clear SH and reduce choroidal new vessel activity.

Exudative age-related macular degeneration (AMD) is the most frequent cause of acute submacular hemorrhage (SMH). Without treatment the formation of a macular scar with poor visual function is the usual outcome. While several surgical treatment approaches have been proposed to date, there is no general consensus regarding optimal treatment of acute SMH. Vitrectomy with subretinal co-application of recombinant tissue plasminogen activator (rtPA) and bevacizumab followed by a gas tamponade is a new approach which has shown promising functional results in clinical studies. The aim of the co-application of rtPA and bevacizumab is to simultaneously displace the submacular hemorrhage from the fovea and to effectively reduce choroidal new vessel activity. Experimental studies have shown that rtPA and bevacizumab are compatible in a co-application.

Aim: To evaluate short-term and long-term outcomes of subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and bevacizumab followed by intravitreal injections of bevacizumab or ranibizumab for neovascular age-related macular degeneration with submacular haemorrhage (SMH)., Methods: Retrospective, consecutive, interventional case series of 41 eyes of 40 patients. All patients underwent pars plana vitrectomy with subretinal coapplication of rtPA and bevacizumab and intravitreal gas tamponade. Postoperatively, repeated intravitreal injections of bevacizumab or ranibizumab were applied following a flexible, predominantly visual acuity-driven re-treatment regimen., Results: Mean diameter of SMH was 4.5 disc diameters (range 1.5-12). Complete displacement of SMH was achieved in 35 of 41 eyes. Large and prominent SMH extending beyond the vascular arcades were completely displaced in six of eight eyes. SMH recurred in eight eyes after a mean of 9.1 months (2-19). A mean of 4.5 (2-9) intravitreal anti-vascular endothelial growth factor injections were applied during 12 months postoperatively. Short-term (3 months, n=41), mean best corrected logMAR visual acuity (BCVA) improved significantly from the preoperative value 1.7 (3.0-0.5) to 0.8 (1.6-0.2). 12 eyes had reading ability (≤logMAR 0.4) and 29 eyes had gained ambulatory visual acuity (≤logMAR 1.6). Long-term (mean 17 months (12-32), n=26) BCVA was 0.9 (1.6-0.1). Compared with short-term, BCVA had decreased in 12 of 26 eyes., Conclusion: The operation effectively displaces small and large SMHs. In the long-term, a predominantly visual acuity-driven re-treatment regimen puts the initial functional improvement at risk. More sensitive re-treatment parameters may help to improve long-term functional outcome.

Aim: To compare the efficacy of pars plana vitrectomy (ppV) with intravitreal injection of recombinant tissue plasminogen activator (rtPA) and gas versus ppV with subretinal injection of rtPA and intravitreal injection of gas., Methods: Nonrandomized, retrospective, interventional, comparative consecutive series including 47 patients with submacular hemorrhage. Eighteen patients were treated with ppV, intravitreal injection of rtPA and 20% SF6 gas [group A: mean age 78 years, mean duration of symptoms 6.6 days, 15 age-related macular degeneration (AMD), three retinal arterial macroaneurysm (RAMA)]. Twenty-nine patients were treated with ppV, subretinal injection of rtPA and intravitreal injection of SF6 gas (group B: mean age 75 years, mean duration of symptoms 5.9 days, 26 AMD, two RAMA, one blunt ocular trauma). The main outcome measure was complete displacement of submacular hemorrhage from the fovea., Results: Complete displacement of submacular hemorrhage was achieved in less patients in group A (22%) than in group B (55%) (p = 0.025). In group A, mean best-corrected visual acuity (BCVA) change was logMAR -0.14, standard deviation (SD) = 0.64, and in group B logMAR -0.32, SD = 0.68 without statistically significant difference between the two groups (p = 0.2, Mann-Whitney test). Complications (retinal detachment, vitreous hemorrhage, and recurrence of submacular hemorrhage) were more frequent in group B than in group A., Conclusion: ppV with subretinal injection of rtPA and intravitreal injection of gas was more effective than ppV with intravitreal injection of rtPA and gas in terms of complete displacement of submacular hemorrhage; however, it may be associated with a higher rate of postoperative complications. Functional improvement in the majority of patients suggests the absence of direct retinal toxicity of subretinally applied rtPA.

Aim: To evaluate the efficacy and safety of pars plana vitrectomy (ppV) with subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and bevacizumab, and fluid-gas exchange for neovascular age-related macular degeneration (AMD) with submacular haemorrhage (SMH)., Methods: Consecutive interventional case series of 12 patients with neovascular AMD with SMH with a maximum history of 14 days. All patients underwent ppV with subretinal coapplication of rtPA and bevacizumab, and fluid-gas (20% SF6) exchange. Phakic patients underwent concomitant cataract surgery. Additional injections of bevacizumab were applied intravitreally 4 and 8 weeks postop., Results: Complete displacement of SMH from the fovea was achieved in 9 of 12 patients. The mean best-corrected visual acuity (BCVA) improved significantly from preop logMAR 1.9 (range 3.0 to 0.7) to logMAR 1.2 (range 3.0 to 0.3) at 4 weeks postop (p = 0.01) and to logMAR 0.9 (range 1.6 to 0.2) at 12 weeks postop (p = 0.006). The mean improvement of BCVA 4 weeks postop as compared with preop was logMAR 0.7 (range -0.2 to 2.3). The mean improvement of BCVA 12 weeks postop as compared with preop was logMAR 0.96 (range -0.3 to 2.8). Overall, at 12 weeks postop, BCVA had improved in 10 patients, remained unchanged in one patient and worsened in one patient., Conclusion: PpV with subretinal coapplication of rtPA and bevacizumab, and fluid-gas exchange effectively displaces SMH and improves visual acuity in most patients.