Lars-Olof Hattenbach

Intravitreous injection of tissue plasminogen activator and gas in the treatment of submacular hemorrhage under various conditions

OBJECTIVE To investigate the efficacy and safety of treating submacular hemorrhages secondary to age-related macular degeneration (ARMD) with intravitreous recombinant tissue plasminogen activator (rt-PA) and gas under various conditions. DESIGN Prospective, noncomparative case series. PARTICIPANTS Forty-three consecutive eyes of 42 patients with recent (range, 2-28 days) subfoveal hemorrhage secondary to ARMD were included in this study. The size of subretinal hemorrhage ranged from 0.25 to 30 disc areas. METHODS All patients were treated with intravitreous injections of rt-PA (50 microg) and sulfur hexafluoride (0.5 ml). Postoperative prone positioning was maintained for 24 to 72 hours. Patient follow-up ranged from 4 to 18 months (mean, 6 months). MAIN OUTCOME MEASURES Best and final postoperative visual acuity in relation to size and onset of hemorrhage, displacement of subretinal blood, and surgical complications. RESULTS Best postoperative visual acuity compared with preoperative visual acuity was improved two or more Snellen lines in 19 eyes (44%) and stable in 24 eyes (56%). Final visual acuity was improved two or more lines in 13 eyes (30%), stable in 26 (61%), and two or more lines worse in 4 eyes (9%). Duration of hemorrhage <or=14 days was associated with a better gain of lines of vision (P = 0.0058). Best postoperative acuity was maintained for an average of 4.2 months (range, 0.5-12 months). Overall, complete displacement of blood from under the fovea was achieved in 35 eyes (81%). Nine eyes (21%) developed recurrent hemorrhage, which required repeat treatment. In three patients (7%), a mild breakthrough vitreous hemorrhage was observed. CONCLUSIONS Our findings suggest that intravitreous injections of rt-PA and gas are of value for an improved and accelerated visual recovery in ARMD patients with submacular hemorrhage, although final visual outcome is often limited by the progression of the underlying ARMD. Patients with retinal hemorrhages of recent onset (<or=14 days) seem to have the most favorable results. A rapid displacement of submacular blood may reveal discrete choroidal neovascular membranes amenable to further treatment. The complication rate of this minimally invasive technique seems to be low.

Intravenous Thrombolysis With Low-dose Recombinant Tissue Plasminogen Activator in Central Retinal Artery Occlusion

PURPOSE To evaluate the beneficial effect of intravenous thrombolysis aiming at rapid restoration of blood flow during the early hours of a central retinal artery occlusion (CRAO). DESIGN Interventional case series. METHODS In the present study, we prospectively evaluated the visual outcome after thrombolytic treatment with low-dose (50 mg) rt-PA (recombinant tissue plasminogen activator) and concomitant intravenous heparinization in patients with acute CRAO, best-corrected visual acuity (BCVA) < or = 20/100, and onset of symptoms within 12 hours prior to treatment. RESULTS Twenty-eight patients (28 eyes) were included in this study. Final visual acuity was improved three or more lines in nine eyes (32%), stable in 18 (64%), and worse in one eye. Time to treatment < or = 6.5 hours was associated with a better gain of lines of vision (P = .004). Seven of 17 eyes (41%) that received thrombolytic treatment within the first 6.5 hours achieved a final BCVA > or = 20/50, compared to none in the subgroup of patients with onset to treatment >6.5 hours (P = .023). We observed no serious adverse events. CONCLUSIONS Our findings indicate that thrombolytic treatment with intravenous low-dose rt-PA is of value for an improved visual recovery in patients with acute CRAO, if administered within the first 6.5 hours after the onset of symptoms.

Risk Factors for Complications After Congenital Cataract Surgery without Intraocular Lens Implantation in the First 18 Months of Life

PURPOSE To determine individual risk factors for the development of postoperative complications after pediatric cataract surgery in the first 18 months of life. DESIGN Interventional, consecutive case series. METHODS We retrospectively reviewed the records of 71 eyes of 46 children who underwent surgery for congenital cataract within the first 18 months of life. A limbal approach bimanual lens aspiration, posterior capsulorrhexis, and anterior vitrectomy without intraocular lens implantation was performed in all children. We examined the interrelationships of operative and postoperative complications with other variables such as patient age, family history, or ocular abnormalities. The mean follow-up period was 39 months. RESULTS The most frequent postoperative complications were late-onset open-angle glaucoma (10.8%) and vitreous hemorrhage (10.8%), whereas early-onset glaucoma (4.6%) was less common. Secondary cataract was observed in seven eyes (9.2%). We determined a family history of aphakic glaucoma in first-degree relatives (P = .007) as well as cataract surgery in the first three months of life (P = .039) and nuclear cataracts (P = .0009) to be strong predictors of late-onset glaucoma. Secondary cataract formation was associated strongly with lensectomy in the first five months of life. The diagnosis of postoperative hemorrhages was associated significantly with the presence of persistent fetal vasculature (P < .0001). CONCLUSIONS Patients with preoperative predictors at presentation such as young age at the time of surgery, a family history of aphakic glaucoma, nuclear cataract, or persistent fetal vasculature syndrome offer a clear target for extensive postoperative care after congenital cataract surgery.

High prevalence of resistance to APC in young patients with retinal vein occlusion.

Abstract. Resistance to activated protein C (APC) is among the coagulation disorders that have been implicated in retinal vein occlusion. However, since retinal vascular occlusions may be due to a combination of several mechanisms, the question of whether thrombophilic anomalies are pathogenic for this disorder remains controversial. In the current study, we investigated the prevalence of APC resistance in patients with retinal vein occlusion with reference to age and various cardiovascular risk factors. A cohort of 142 consecutive patients with retinal vein occlusion and a control group of 128 subjects matched for age, sex and several risk factors were screened for resistance to APC. Both cohorts were divided into two subgroups, according to the patients age (≤45 or >45 years) at the time of the retinal vein occlusion or a previous thromboembolic event. The proportion of individuals with resistance to APC was higher in the patient group (13 of 142; 9.1%) when compared to controls (6 of 128; 4.7%). Moreover, patient age ≤45 years by the time of the retinal vein occlusion or a previous thromboembolic event was significantly associated with a high prevalence of APC resistance (17%). By contrast, resistance to APC was present in 5 of 95 cases (5.3%) in the patient group >45 years and in 4 of 83 (4.8%) young controls. Our results indicate that APC resistance is highly prevalent in patients with retinal vein occlusion at age ≤45 years and/or with a history of thrombosis at this age. By contrast, the prevalence of APC resistance in patients who suffered a retinal vein occlusion when they were older than 45 years and had no history of thromboembolism appears to be similar to that seen in healthy control subjects or in the normal population. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects.

Fibrinolytic Therapy with Low-Dose Recombinant Tissue Plasminogen Activator in Retinal Vein Occlusion

Fibrinolytic therapy aimed at early restoration of blood flow appears to be a promising therapeutic approach in haemorrhagic retinopathy. The risk of bleeding complications, a major problem with fibrinolysis, can be reduced by the use of low-dose thrombolytic regimens. In our study, 14 patients with ischaemic central (CRVO) or branch (BRVO) retinal vein occlusion who presented with severe visual loss and recent onset of symptoms were treated with a low dose (50 mg) of recombinant tissue plasminogen activator (rt-PA) and intravenous heparin. In 10 of 14 patients (7 CRVO, 3 BRVO), an increase in visual acuity of one line or more on the logarithmic visual acuity chart was noted and in 8 patients (6 CRVO, 2 BRVO) a reduction of areas of capillary non-perfusion was observed, suggesting that a restoration of retinal capillary blood flow can be achieved if fibrinolysis is initiated in the early phase of haemorrhagic retinopathy. In view of the poor prognosis in the natural course of haemorrhagic retinopathy and the potential haemorrhagic risk in fibrinolysis, the use of low-dose rt-PA appears to constitute an encouraging approach in the management of this disease.

Visual Outcome after Treatment with Low-Dose Recombinant Tissue Plasminogen Activator or Hemodilution in Ischemic Central Retinal Vein Occlusion

The ischemic type of central retinal vein occlusion (CRVO) is associated with a poor visual and ocular prognosis. Although several reports have indicated that hemodilution or thrombolytic therapy may be of benefit, there is still no consensus among ophthalmologists about the management of this disorder. In our study, we retrospectively evaluated the visual outcome after medical treatment in 58 patients with ischemic CRVO and severe visual loss (≤20/50). We separately investigated three different groups, depending on the following criteria: onset of symptoms within 11 days prior to admission and thrombolytic treatment with 50 mg of recombinant tissue plasminogen activator (rtPA) and intravenous heparinization (n = 23) or hemodilution therapy (n = 22) or onset of symptoms >11 days before the initial visit and hemodilution (n = 13). An advancement of 2 or more lines on the logarithmic visual acuity chart was noted in 10 cases (44%) in the rtPA group and in 3 subjects (14%) in the early-phase hemodilution group, whereas only 1 patient in the late-phase hemodilution group showed a comparable improvement. Our findings suggest that treatment with low-dose rtPA or hemodilution aimed at early restoration of blood flow has the potential to improve the visual prognosis in ischemic CRVO. The finding that thrombolysis had a favorable outcome supports the hypothesis that specific subgroups of patients may benefit from this therapeutic approach. Further investigation will be required to definitively prove the effectiveness of fibrinolytic agents.

Course of intraocular pressure after intravitreal injection of 0.05 mL ranibizumab (Lucentis).

Purpose This prospective study examines the changes in short-term intraocular pressure (IOP) in patients with wet age-related macular degeneration (AMD) receiving intravitreal injections of 0.05 mL ranibizumab (Lucentis®) in a supine position. Methods A total of 45 eyes (45 patients, 16 M, 29 F, mean age: 78 y) received intravitreal ranibizumab injections for treatment of wet AMD (0.05 mL = 0.5 mg). The IOP was measured by Schiötz tonometry immediately preoperatively and postoperatively, and also after 3 and 10 minutes in a supine position. No history of glaucoma was present. Results The mean preoperative IOP was 22.4±5.5 mmHg in supine position. Immediately after the injection, IOP increased to 47.9±15.1 (range 23–82, p<0.001), with 32 eyes (71.1%) >40 and 19 eyes (42.2%) >50 mmHg. The mean difference between preoperative IOP and immediately after the injection was +25.5±13.6 mmHg. IOP decreased spontaneously by the first 3 minutes after operation by 12.6±6.0 mmHg and after 10 minutes by 21±9.4 mmHg. The mean difference between preoperative IOP and 10 minutes postoperatively was +4.6±7.0 mmHg (range: −9.3 to +25.9 mmHg, p<0.001). Eyes without a subconjunctival reflux had a higher increase in IOP than eyes with any reflux (p<0.001). Conclusions IOP increased significantly in a considerable number of patients after intravitreal ranibizumab injections. A rapid and spontaneous decline was observed in the majority of cases. If there is no subconjunctival reflux after the injection, the increase in IOP is higher than in eyes with any back-flow under the conjunctiva.

Detection of Inducible Nitric Oxide Synthase and Vascular Endothelial Growth Factor in Choroidal Neovascular Membranes

Vascular endothelial growth factor (VEGF) is among the cytokines which have been implicated in the pathogenesis of choroidal neovascularization secondary to age-related macular degeneration (ARMD). There is, however, evidence that intercellular signaling molecules, such as nitric oxide (NO), are involved in this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), which is expressed after induction by cytokines. In the current study, we investigated whether VEGF and iNOS are coexpressed in choroidal neovascular membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and in spatial relation to vessel walls. As scored by light microscopy, we found a significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341) in vascular endothelial cells. Our study supports a significant role for iNOS in the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our findings suggest a possible relationship between NO and VEGF in the regulation of pathologic angiogenesis in this disease.

Subretinal hemorrhages associated with age-related macular degeneration in patients receiving anticoagulation or antiplatelet therapy.

PURPOSE To evaluate the incidence of and risk factors for subretinal hemorrhages in age-related macular degeneration (AMD) patients on anticoagulation or antiplatelet therapy. DESIGN Retrospective, observational case series. METHODS We retrospectively reviewed the medical and photographic records of 71 consecutive patients who sought treatment at our institution with acute subretinal hemorrhages complicating age-related macular degeneration. The size of the subretinal hemorrhage was measured in standardized Macular Photocoagulation Study disc areas. Data on the use of medications and medical indications for anticoagulation and antiplatelet therapy were obtained. RESULTS Overall, patients receiving antithrombotic therapy had a significantly larger subretinal hemorrhage size (mean, 9.71 disc areas) than patients not receiving anticoagulant or antiplatelet therapy (mean, 2.99 disc areas). Subgroup analysis revealed that both antiplatelet (P < .0001) and anticoagulant therapy (P = .003) were associated with a significantly larger bleeding size. Moreover, subgroup analysis among patients with arterial hypertension revealed that individuals receiving antithrombotic therapy had a statistically significantly larger hemorrhage size than hypertensive patients who did not receive anticoagulants or antiplatelet agents (P < .0001). CONCLUSIONS Our results indicate that anticoagulants and antiplatelet agents are strongly associated with the development of large subretinal hemorrhages in AMD patients. Moreover, arterial hypertension is a strong risk factor for large subretinal hemorrhages in AMD patients receiving anticoagulants or antiplatelet agents. Physicians should be aware of an increased risk of extensive subretinal hemorrhage in AMD patients when deciding on the initiation and duration of anticoagulant and antiplatelet therapy.

Intraocular recombinant tissue- plasminogen activator fibrinolysis of fibrin formation after cataract surgery in children

PURPOSE To evaluate the efficacy and safety of intracameral recombinant tissue plasminogen activator (rt-PA) application for fibrinolysis of fibrin formation after cataract surgery in children. SETTING Johann Wolfgang Goethe-University, Department of Ophthalmology, Frankfurt am Main, Germany. METHODS This study comprised 11 eyes of 10 patients aged 3 to 13 years (mean 7.2 +/- 3.68 [SD]) who developed severe fibrin formation after cataract surgery and IOL implantation despite intensive topical steroid therapy. Under general anesthesia, fibrinolysis was performed with 10 micrograms of rt-PA 7.18 +/- 2.04 days after intraocular surgery. Follow-up included slitlamp examination, tonometry, visual acuity testing, and-ophthalmoscopy. Anterior chamber flare measurements could be performed in 6 eyes. RESULTS Complete resolution of fibrin formations occurred in 90% of the patients in these cases, no recurrent fibrinous reaction or adverse effects were noted. In 2 eyes of the same patient with a history of juvenile rheumatoid arthritis and chronic uveitis, fibrin clot dissolution was incomplete. A recurrent fibrinous formation could be observed after 2 and 4 weeks, respectively. A beginning band keratopathy excluding the central and limbal cornea was noted after 6 and 8 weeks, respectively. CONCLUSION Intraocular application of rt-PA appears to be a safe and efficacious therapeutic approach in the management of severe fibrinous reactions after pediatric cataract surgery.