Intravitreal recombinant tissue plasminogen activator without and with additional gas injection in patients with submacular haemorrhage associated with age-related macular degeneration

ArticleinActa ophthalmologica 90(7) · February 2011with 16 Reads
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Abstract
Purpose: To compare intravitreal recombinant tissue plasminogen activator (rt-PA) treatment with and without gas injection in patients with submacular haemorrhage associated with age-related macular degeneration. Methods: We conducted a retrospective, non-randomized comparative case study of 110 eyes from 76 women and 34 men (mean age 78.1 ± 6.9 years). Evaluations of the data were performed for baseline visit (t1), and visits 1–3 weeks (t2), 3 months (t3) and 6 months after (t4). The patients were classified according to gas treatment into group A (without gas, n = 46) and group B (with gas, n = 64) and according to rt-PA-dosage into group A1 and B1 (50 μg), group A2 and B2 (100 μg), and group A3 and B3 (200 μg). Results: At t4, the patients in group A had a median increase of 0.4 logMAR, and those in group B had a decrease of 0.1 logMAR (p = 0.183). The best corrected visual acuity (BCVA) remained stable or increased in 55% and 62% of patients in groups A and B, respectively (p = 0.151), in 50% and 68% of patients in groups A1 and B1, respectively (p = 0.620), in 40% and 100% of patients in groups A2 and B2, respectively (p = 0.250), and in 75% and 63% of patients in groups A3 and B3, respectively (p = 0.463). Complications were observed in 13.6% of patients. Conclusions: Best results were obtained in patients treated with 50 and 100 μg of rt-PA and in those cases BCVA development was more beneficial if additional gas was injected.

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  • Article
    Full-text available
    PurposePneumatic displacement of submacular hemorrhages (SMHs) with intravitreal injection of sulfur hexafluoride (SF6) gas with or without tissue plasminogen activator (tPA) and prone posturing is an effective minimally invasive treatment. We observed some cases in which simultaneous flattening of hemorrhagic pigment epithelial detachments (PEDs) occurred after prone posturing. This study evaluated the impact of pneumatic displacement using tPA to treat PEDs and visual outcomes in eyes with SMHs secondary to neovascular age-related macular degeneration (AMD). Methods This retrospective analysis reviewed the medical records of 32 patients (33 eyes) who underwent pneumatic displacement for AMD-associated SMHs. The SMHs were related to polypoidal choroidal vasculopathy (PCV) in 24 eyes and typical AMD in nine eyes and treated with intravitreal injection of SF6 gas with tPA. We assessed the postoperative best-corrected visual acuities (BCVAs), prevalence and flattening rates of the PEDs, and the number of additional treatments. ResultsThe mean follow-up period was 35.4 ± 19.8 months. The BCVAs improved significantly in eyes with PCV compared with eyes with typical AMD. Thirty-one (93.9%) of 33 eyes had an accompanying PED. The PEDs flattened in 14 (58.3%) of 24 eyes with PCV but in only one (14.3%) of seven eyes with typical AMD (p = 0.04). A mean of one additional treatment was administered during the first year in 15 eyes with flattened PEDs, which was significantly (p < 0.05) fewer than the 3.6 additional treatments in 16 eyes with persistent PEDs. ConclusionsPEDs often accompany SMHs secondary to neovascular AMD. Pneumatic displacement of the SMHs using tPA unexpectedly flattened the PEDs, especially in eyes with PCV, and was associated with fewer additional treatments.
  • Article
    To investigate the causes of acute spontaneous submacular hemorrhage with indocyanine green angiography (ICGA). Retrospective observation case series. A total of 51 eyes from 51 patients with newly developed spontaneous submacular hemorrhage were enrolled. Best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, spectral domain optical coherence tomography (OCT), and ICGA at baseline were analyzed. The extent of hemorrhage using fundus photography, height of hemorrhage, and central foveal thickness measured by OCT was analyzed to compare the diagnostic and nondiagnostic groups. The mean logarithm of the minimum angle of resolution (logMAR) BCVA at presentation was 1.21 ± 0.74 (Snellen equivalent, 20/324); the mean follow-up period was 23.9 ± 23.9 months. The cause of submacular hemorrhage was diagnosed in 43 of 51 eyes (84.3%) based on ICGA at presentation. The initial diagnoses were correct in 93% of eyes. In 3 cases, the initial diagnosis of age-related macular degeneration (AMD) was changed to polypoidal choroidal vasculopathy (PCV) based on follow-up ICGA. The central foveal thickness was significantly greater in the nondiagnostic group (1,102.4 vs. 666.7 μm, respectively; p = 0.008). The most common cause of submacular hemorrhage was neovascular AMD (52.9%), followed by PCV (37.3%), macroaneurysm (5.9%), and lacquer crack (3.9%). The mean final visual acuity was generally worse in patients with submacular hemorrhage with typical AMD (visual acuity 20/618) or PCV (visual acuity 20/240) compared to that in patients with retinal macroaneurysm (visual acuity 20/100) or lacquer crack (visual acuity 20/72). ICGA at initial presentation helps identify causes of submacular hemorrhage, allowing differential treatment approaches that may improve outcomes and safety. © 2015 S. Karger AG, Basel.
  • Article
    Full-text available
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  • Article
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  • Article
    To investigate the outcomes of vitrectomy, subretinal tissue plasminogen (tPA) injection, gas tamponade, and upright positioning in patients with hemorrhagic neovascular age-related macular degeneration (AMD). Retrospective, noncomparative case series. Records of patients who were diagnosed with submacular hemorrhage secondary to neovascular AMD and underwent treatment with the combined method between 2004 and 2010 were reviewed. The main outcome measure was the difference between preoperative and post-operative best corrected visual acuity (BCVA). In 10 eyes of 10 patients, mean preoperative and postoperative BCVA values were 1.75 and 1.23 logMAR, respectively (P = .011), after a mean follow-up time of 38.7 ± 26.5 months (range: 10 to 71 months). Eight of 10 patients (80%) gained at least three lines. In patients with hemorrhagic neovascular AMD, treatment with vitrectomy, subretinal tPA injection, gas tamponade, and upright positioning was associated with better visual outcomes than those reported for patients with untreated disease. [Ophthalmic Surg Lasers Imaging Retina. 2013;44:471-476.].
  • Article
    Aims: To review and discuss the literature on recombinant tissue plasminogen activator (rtPA) for the treatment of a recent-onset submacular hemorrhage in patients with age-related macular degeneration. Methods: The administration technique of rtPA, the use of additional gas and vascular endothelial growth factor inhibitors (anti-VEGF), and the displacement rate of submacular hemorrhage and complications were noted from published reports, and a case series from the Rotterdam Eye Hospital (REH). Results: 38 studies with a total of 1,185 patients (1,176 eyes), and 28 patients from the REH were analyzed. Several methods for rtPA administration are available, which can be divided into two groups: submacular rtPA administration with vitrectomy; or intravitreal rtPA administration without vitrectomy. In both groups, the administration of gas and/or anti-VEGF agents could be additional. There appears to be no clear difference in complete displacement or complication rate between the more or the less invasive treatment groups. Conclusion: Although intravitreal injection of rtPA and gas only was reported to be as effective as subretinal rtPA with vitrectomy and gas, recent studies tend to use vitrectomy. These data underscore the need for a randomized controlled trial to choose the most effective and safe method of rtPA administration.
  • Article
    A case report is presented of a 20-year-old man, who had posttraumatic choroidal rupture and thick submacular haemorrhage. The haemorrhage was successfully removed with vitrectomy and intraoperative fibrinolysis with subretinal tissue plasminogen activator. Six months postoperatively the visual acuity was 0.7 (6/9).
  • Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study
    • Macular
    • Study
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    • Macular
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  • Intravitreal gas and tPA: an outpatient procedure for subretinal haemorrhage
    • W Heriot
    Heriot W (1996): Intravitreal gas and tPA: an outpatient procedure for subretinal haemorrhage. Vail Vitrectomy Meeting, Vail, CO.
  • 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
    Background We previously reported retinal toxic reactions in rabbit eyes receiving intravitreal injections of commercial tissue plasminogen activator (tPA) in concentrations greater than or equal to 50 µg/0.1 mL, and recent clinical experience suggests that intravitreal tPA solution may produce toxic effects in human eyes. We therefore investigated the dose-dependent retinal toxicity of intravitreal commercial recombinant tPA solution in cat eyes, which have a vascularized inner retina and vitreous volume similar to that of human eyes. Methods Commercial tPA in L-arginine solution was injected into the mid vitreous cavity of normal cat eyes in doses of 25, 50, 75, and 100 µg/0.1 mL and 200 µg/0.2 mL. Control (fellow) eyes received an equal volume of sterile saline solution. After injection, eyes were evaluated by ophthalmoscopy and electroretinography for 14 days and then enucleated for histopathological evaluation. Results Fundus pigmentary alterations were observed in eyes receiving doses greater than or equal to 50 µg/0.1 mL. Changes were centered in the area around the injection site, and the area's size increased in proportion to the dosage. Mean electroretinography B-wave amplitude measured at 14 days was significantly reduced in eyes receiving greater than or equal to 50 µg of tPA in a dose-dependent fashion. Light microscopy of the involved areas showed loss of photoreceptor elements with necrosis and proliferation of the retinal pigment epithelium. Conclusion Intravitreal injection of commercial tPA solution results in dose-dependent retinal toxicity in cat eyes. Clinical Relevance Because cat eyes are similar to human eyes regarding retinal vascularity and vitreous volume, intravitreal injections of commercial tPA (with L-arginine vehicle) in concentrations greater than 25 µg/0.1 mL are potentially unsafe in human eyes.
  • Article
    A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons ≥50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen ≥63μm, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.
  • Article
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  • Article
    Objective To investigate the efficacy of intravitreous bevacizumab and sulphur hexafluoride (SF6) for treating submacular hemorrhage secondary to age-related macular degeneration (ARMD). Methods Ten eyes of 10 patients (mean age 78.4 years, ±6.5) with recent (range 1–4 weeks, median 1.0, mean 1.5) subfoveal hemorrhage secondary to ARMD were included in this study. The size of the subretinal hemorrhage ranged from 0.85 to 21.7 mm2 (median 6.6 mm2, mean 9.5 mm2, ±8.12). All patients received combined intravitreous injections of 1.25 mg bevacizumab and 0.3 ml SF6. Follow-up visits were done 4 weeks after treatment. Depending on the ophthalmologic findings, further treatment with antivascular endothelial growth factor (anti-VEGF) injections was planned. Results Visual acuity improved three or more Snellen lines in six eyes (60%), remained stable in three (30%), and worsened by three or more lines in one eye (10%). Overall, displacement of blood was achieved in eight eyes (80%). In the following months, nine eyes received further injections with VEGF inhibitors. The Wilcoxon paired sample test revealed significant improvement of visual acuity in our patients (p=0.05). Conclusions Our findings suggest that combined intravitreous injections of bevacizumab and SF6 have the potential to improve visual outcome in patients with subretinal hemorrhage secondary to ARMD. However, further treatment of the underlying choroidal neovascularization is mandatory.
  • Article
    Purpose Treatment of submacular hemorrhage with recombinant tissue plasminogen activator(rt-PA) and SF6 induces blood displacement out of the fovea by maintaining prone positioning. The underlying disease, e.g. the choroidal neovascularisation remains untreated. Nevertheless, it has been noted that the visual results of this method are more favorable than those expected in the natural course. Contributing long-term results the present study intends to give more information concerning this phenomenon. Method A total of 45 consecutive eyes were treated using a standardized procedure (duration of hemorrhage ≤1week, area of hemorrhage 1–10 disc areas, 50 γg rt-PA, 0.5 ml SF6 24 h later, prone positioning for 3 days). Those with a follow-up of ≥6 months were included in the study. Results From 25 patients a total of 25 eyes fulfilled the criteria. Postoperative visual acuity(3–7 days) was improved or unchanged in 19 eyes and worse in 6 eyes. Comparison of postoperative visual acuity after follow-up of an average of 14.2 months (range 6–28 months) revealed an improvement in 10 eyes, no change in 7 eyes and a deterioration in 8 eyes. A second treatment was performed in 2 eyes and photocoagulation in 1 eye. Conclusion After more than 1 year the postoperative visual acuity was stable or even better in about two-thirds of the eyes therefore treatment with rt-PA and SF6 may also influence the choroidal neovascularisation.
  • Article
    Full-text available
    In a retrospective review, the functional effects of intra-vitreal ranibizumab monotherapy in patients with sub-foveal haemorrhage secondary to choroidal neovascularisation (CNV) in age-related macular degeneration (ARMD) are reported. Twelve eyes of 12 patients were treated with intra-vitreal ranibizumab (0.5 mg in 0.05 ml) in accordance with current practice. Follow-up was arranged at monthly intervals. Eleven patients completed 6 months and seven completed 12 months of follow-up. Duration of haemorrhage, lesion size, ETDRS letter score at baseline, and follow-up were analysed. The mean time for complete clearance of sub-retinal haemorrhage was 4.7 months (range 3-7 months). After 6 months, visual acuity was stable or improved in 7 of 11 eyes and the mean change in ETDRS letter score was +7.6 letters (P>0.05). After 12 months, visual acuity was stable or improved in five of seven eyes and the mean change in ETDRS letter score was +7.3 letters (P>0.05). For the seven cases with 12 months of follow-up, a mean of six injections were given. Two patients had a decrease in acuity of >15 ETDRS letters during follow-up. No other local or systemic side-effects were reported. Intra-vitreal ranibizumab monotherapy may be an effective treatment for sub-foveal haemorrhage secondary to CNV in ARMD.
  • 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. 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. 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. 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.
  • Article
    To investigate the efficacy of intravitreous bevacizumab and sulphur hexafluoride (SF(6)) for treating submacular hemorrhage secondary to age-related macular degeneration (ARMD). Ten eyes of 10 patients (mean age 78.4 years, +/-6.5) with recent (range 1-4 weeks, median 1.0, mean 1.5) subfoveal hemorrhage secondary to ARMD were included in this study. The size of the subretinal hemorrhage ranged from 0.85 to 21.7 mm(2) (median 6.6 mm(2), mean 9.5 mm(2), +/-8.12). All patients received combined intravitreous injections of 1.25 mg bevacizumab and 0.3 ml SF(6). Follow-up visits were done 4 weeks after treatment. Depending on the ophthalmologic findings, further treatment with antivascular endothelial growth factor (anti-VEGF) injections was planned. Visual acuity improved three or more Snellen lines in six eyes (60%), remained stable in three (30%), and worsened by three or more lines in one eye (10%). Overall, displacement of blood was achieved in eight eyes (80%). In the following months, nine eyes received further injections with VEGF inhibitors. The Wilcoxon paired sample test revealed significant improvement of visual acuity in our patients (p=0.05). Our findings suggest that combined intravitreous injections of bevacizumab and SF(6) have the potential to improve visual outcome in patients with subretinal hemorrhage secondary to ARMD. However, further treatment of the underlying choroidal neovascularization is mandatory.
  • 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
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  • Article
    We reviewed the charts of 29 patients with large subretinal hemorrhages involving the center of the fovea to evaluate factors that might be prognostic of visual outcome. The average final visual acuity was 20/480 with a mean follow-up of three years. Patients with thick hemorrhages (causing an obvious elevation of the fovea) had worse final visual acuity than patients with thin hemorrhages (P = .02). The diameter of the hemorrhage was not a significant predictor of outcome. Patients with aging macular degeneration had poorer final visual acuity (mean, 20/1,700, P = .002), and patients with choroidal ruptures had better final visual acuity, (mean 20/35, P less than .001) than the remainder of the patients. We found that the presence of aging macular degeneration was a more important predictor of the outcome of legal blindness than the thickness of the hemorrhage (P = .03). Although the prognosis in patients with subfoveal blood is generally poor, some patients have excellent return of vision.
  • Article
    We analyzed data of 50 patients receiving long-term warfarin sodium therapy who underwent ocular surgery between 1982 and 1986. The frequency of hemorrhagic and thrombotic complications was compared in patients in whom anticoagulants were continued, those in whom the anticoagulants were discontinued in the perioperative period, and a group of matched control patients. There were six perioperative hemorrhagic complications in the warfarin-treated group (12%) compared to none in the control group. This difference was significant (P less than .03). However, no significant difference in hemorrhagic complications was seen between patients in whom warfarin sodium was continued and those in whom it was discontinued.
  • Article
    A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.
  • Article
    Tissue plasminogen activator (tPA) (250 micrograms/ml) was used to facilitate removal of submacular thrombus in 15 patients. Following a three-port vitrectomy and subretinal tPA injection (0.1 ml) via a 30 gauge needle, blood was evacuated after enzymatic dissolution for 20 minutes. Two injections were required in some cases. Nine women and six men were treated (mean age 75.5 +/- 8.6 years). Duration of symptoms ranged from 2 days to 8 weeks. One case was due to a retinal macroaneurysm, the others to age-related macular degeneration. Vision improved in 13 patients and remained the same or deteriorated in 2 (mean follow-up 11 +/- 4.9 months). Well-defined subretinal neovascular membranes were identified in 2 patients and occult neovascularisation suspected in 2 others. A cataract developed in 1 case and retinal detachments in 2 others; all were treated successfully. The poor visual prognosis associated with submacular haemorrhage may be obviated by the use of the technique we describe.
  • Article
    To assess the result of surgical removal of submacular hemorrhage by using tissue plasminogen activator and perfluorocarbon liquid. In 22 consecutive patients (22 eyes), subretinal hemorrhage associated with age-related macular degeneration, which involved the fovea and completely obscured the choroidal vascular pattern, was treated by pars plana vitrectomy. The hemorrhages were liquefied with tissue plasminogen activator, squeezed into the vitreous cavity with perfluorocarbon liquid, and then evacuated. Efficacy of the procedure was judged by the best postoperative corrected visual acuity, which was 20/100 or better in 16 eyes (73%). Submacular hemorrhage recurred in four (18%) eyes, epiretinal membrane formed in three (14%) eyes, and retinal detachment occurred in three (14%) eyes. Best-corrected final visual acuity was improved postoperatively in 18 (82%) of the 22 eyes, unchanged in three (14%) eyes, and decreased in one (5%) eye, final visual acuity was 20/200 or better in 15 eyes (68%) and limited in other eyes by subretinal hemorrhage of greater than 30 days' duration or subfoveal neovascularizations. Use of tissue plasminogen activator and perfluorocarbon liquid in surgical removal of submacular hemorrhage may improve the outcome of surgery by reducing surgically induced retinal damage.
  • Risks of intravitreous injection: a comprehensive review
    • Rd Jager
    • Lp Aiello
    • Sc Patel
    • Et Cunningham
    • Jr
    Jager RD, Aiello LP, Patel SC & Cunningham ET Jr (2004): Risks of intravitreous injection: a comprehensive review. Retina 24: 676–698.
  • Article
    The authors describe the natural history of subfoveal subretinal hemorrhage (for which laser treatment was not indicated) in age-related macular degeneration. A retrospective review of data was performed at a tertiary retinal referral center for 41 eyes from 40 patients with age-related macular degeneration examined during an 18-month period. All patients had at least 3 months of follow-up, as well as subfoveal subretinal hemorrhage that made up more than 50% of a neovascular lesion-as documented by fluorescein angiography-and therefore, did not meet criteria for laser treatment. The number of lines of visual acuity lost or gained in each eye during follow-up was calculated; presenting characteristics were evaluated as predictors of visual outcome. A progressive loss of visual acuity from baseline was observed throughout the 3-year follow-up period in most eyes. At 36 months, a mean of 3.5 lines of visual acuity had been lost in the 16 eyes examined; 44% of eyes had lost 6 or more lines of visual acuity. The percentage of patients who sustained a spontaneous improvement of 3 or more lines of visual acuity decreased from 31% at 12 months to 21% at 36 months of follow-up. Univariate linear regression analysis demonstrated significant relationships of initial size of the hemorrhage, elevation of the retina by the hemorrhage, and size of the entire lesion with visual outcome at the 12-month and 36-month examinations (P < 0.05). Although this study confirms that some eyes with subfoveal subretinal hemorrhage associated with age-related macular degeneration have poor prognoses, the visual acuity of other eyes did not deteriorate. These findings underscore the importance of evaluating the role of therapeutic interventions such as surgery to remove subretinal hemorrhage in randomized clinical trials.
  • Article
    Full-text available
    Despite age-related macular degeneration (AMD) being the commonest cause of blindness amongst the elderly in Western society, the incidence of new lesions is poorly documented and the natural history of existing disease remains ill understood. To document in an elderly population the incidence of new AMD lesions and the progression of pre-existing AMD over time. Baseline ophthalmic examinations were performed on a geographically defined random population sample of elderly people in 1982-4, and retinal photographs taken. The present study re-examined and re-photographed survivors after approximately 7 years using the same fundus camera. Photographs were randomly encoded, and independently graded for AMD features by two masked observers using the Wisconsin AMD grading system. Disagreements were resolved by review to reach a consensus. Eighty-two of the 88 participating survivors had photographs of gradable quality on both occasions in at least one eye. Mean age at follow-up was 87 years (range 84-97 years) and 70.7% of subjects were female. Paired photographs were available on 158 eyes, and showed important differences in drusen type, drusen area and characteristics of the retinal pigment epithelium (RPE) between initial and subsequent examinations. The 7 year incidence (and regression) of lesions was: drusen 30.6% (20.0%), RPE degeneration 54.5% (8.8%), increased pigment 11.6% (64.7%), subretinal haemorrhage 1.3%, subretinal scar/fibrin 1.3% and geographic study 1.3%. These unique population-based results provide new insight into the natural history of AMD in an elderly population.
  • 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 define the natural course of extensive submacular hemorrhage in age-related macular degeneration (AMD). The clinical charts of 54 patients (60 eyes) older than 55 years with subretinal hemorrhage larger than 1 disk diameter and extending beneath the fovea were retrospectively reviewed. The age of the patient, the use of antihypertensive or anticoagulant medication, visual acuity, biomicroscopic and fluorescein and indocyanine green (in 33 cases) angiographic data were recorded at presentation and during follow-up. At the initial examination, average visual acuity was 20/240 (range from 20/70 to light perception). During follow-up (mean 24 months) visual acuity worsened in 80% of the eyes with a mean final visual acuity of 20/1, 250 (range from 20/100 to light perception). The initial size and thickness of hemorrhage were correlated with initial and final visual acuity. Recurrence of hemorrhage resulted in an important impact on final visual acuity. Anatomic outcome showed fibrous tissue proliferation in 23 eyes (38.3%), atrophic scar in 15 eyes (25%) and occurrence of a retinal pigment epithelium tear in 13 eyes (21.6%). The visual outcome in eyes with submacular hemorrhages due to AMD is very poor. Size and thickness of the hemorrhage influenced negatively the natural prognosis. A surgical approach can be considered although it has not yet a widespread use.
  • Article
    Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacular hemorrhage. It is usually used intraoperatively, but may not provide enough time for effective fibrinolysis, especially for a large hemorrhage. The present study was conducted to evaluate the efficiency and safety of preoperative use of TPA for large submacular hemorrhages. Five eyes with large submacular hemorrhage secondary to age-related macular degeneration underwent subretinal injection of TPA in the office 24 hours before surgery. All hemorrhages were less than seven days old and at least 3 mm thick. Preoperative visual acuity ranged from counting fingers to hand motion (HM). Patient follow-up ranged from 3 months to 24 months (mean, 11 months). Final visual acuity ranged from 20/30 to HM. Four of the five eyes (80%) showed improved visual acuity after surgery and 3/5 (60%) attained visual acuity of 20/200 or better. Preoperative use of TPA for drainage of large submacular hemorrhage appears to be safe and may result in efficient clot removal. The true efficacy of TPA in the treatment of submacular hemorrhage can only be proven by a prospective randomized trial.
  • Article
    To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 microg was performed. Gas instillation (0.2-0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 microg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD.
  • Article
    Age-related macular degeneration (ARMD) is the most prevalent cause of blindness in the elderly population. This study retrospectively evaluated the natural course of submacular hemorrhage related to ARMD. We reviewed the records of patients with submacular hemorrhage and foveal avascular zone involvement at the Veterans General Hospital-Taipei from 1981 to 1996. Data were collected from color fundus pictures, fluorescence angiographic films and visual acuity changes. Data from a total of 86 eyes with age-related macular degeneration (ARMD) and 37 non-ARMD eyes were collected. Analysis of data from the ARMD group revealed 10.5% visual acuity improvement six months after presentation and a final mean acuity of 0.069. Analysis of data from the non-ARMD group revealed 29.7% visual acuity improvement and a final mean acuity of 0.388. In this study, patients with submacular hemorrhage had spontaneous visual improvement even without surgery, especially those without subretinal neovascularization.
  • 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.
  • Article
    Some success has been reported with the intravitreal use of tissue plasminogen activator (tPA) and perfluoropropane gas in the management of large submacular hemorrhages. However, the dosage of tPA that has been used (100 micrograms) has a narrow margin of safety, and it remains to be shown that intravitreal tPA can cross the retina and effect subretinal clot lysis. We carried out a pilot study to evaluate the efficacy of intravitreally administered sulfur hexafluoride (SF6) gas alone in the management of large submacular hemorrhages secondary to age-related macular degeneration (AMD). Three patients with large submacular hemorrhages secondary to AMD seen at a university-affiliated teaching hospital in Ottawa were treated with an intravitreal injection of 0.6 mL of SF6 gas. They were instructed to assume a prone position for 7 to 10 days. The patients were followed 3, 7, 14 and 28 days after the procedure and monthly thereafter for at least 6 months. Colour photography and fluorescein and indocyanine green angiography were performed immediately before and 2 weeks after the procedure and, thereafter, at the discretion of the treating ophthalmologist. In all three cases significant inferior displacement of the submacular blood was observed. Two patients showed an improvement of vision from counting fingers to 20/70 and to 20/200. In one case the submacular blood was displaced such that laser photocoagulation of a juxtafoveal choroidal neovascular membrane became possible. The results suggest that intravitreally administered SF6 alone may have a role in the management of selected cases of neovascular AMD complicated by significant submacular hemorrhage. These results call into question the utility of adjunctive intravitreal tPA in such cases.
  • Article
    We previously reported retinal toxic reactions in rabbit eyes receiving intravitreal injections of commercial tissue plasminogen activator (tPA) in concentrations greater than or equal to 50 microg/0.1 mL, and recent clinical experience suggests that intravitreal tPA solution may produce toxic effects in human eyes. We therefore investigated the dose-dependent retinal toxicity of intravitreal commercial recombinant tPA solution in cat eyes, which have a vascularized inner retina and vitreous volume similar to that of human eyes. Commercial tPA in L-arginine solution was injected into the mid vitreous cavity of normal cat eyes in doses of 25, 50, 75, and 100 microg/0.1 mL and 200 microg/0.2 mL. Control (fellow) eyes received an equal volume of sterile saline solution. After injection, eyes were evaluated by ophthalmoscopy and electroretinography for 14 days and then enucleated for histopathological evaluation. Fundus pigmentary alterations were observed in eyes receiving doses greater than or equal to 50 microg/0.1 mL. Changes were centered in the area around the injection site, and the area's size increased in proportion to the dosage. Mean electroretinography B-wave amplitude measured at 14 days was significantly reduced in eyes receiving greater than or equal to 50 microg of tPA in a dose-dependent fashion. Light microscopy of the involved areas showed loss of photoreceptor elements with necrosis and proliferation of the retinal pigment epithelium. Intravitreal injection of commercial tPA solution results in dose-dependent retinal toxicity in cat eyes. Because cat eyes are similar to human eyes regarding retinal vascularity and vitreous volume, intravitreal injections of commercial tPA (with L-arginine vehicle) in concentrations greater than 25 microg/0.1 mL are potentially unsafe in human eyes.
  • Article
    To evaluate a new procedure for displacement of large, thick submacular hemorrhage in patients with age-related macular degeneration. Retrospective review of 11 eyes of 11 patients with age-related macular degeneration and thick submacular hemorrhage (defined as causing retinal elevation detectable on stereo fundus photographs) treated with vitrectomy, subretinal injection of tissue plasminogen activator (25 or 50 microg), and fluid-gas exchange with postoperative prone positioning. Outcome measures included displacement of hemorrhage from the fovea, best postoperative visual acuity, and final postoperative visual acuity. In the 11 affected eyes of 11 patients (seven men and four women; mean age, 76 years), preoperative visual acuity ranged from 20/200 to hand motions. With surgery, subretinal hemorrhage was displaced from the fovea in all 11 cases. Mean postoperative follow-up was 6.5 months (range, 1 to 15 months). Best postoperative visual acuity varied from 20/30 to 5/200, with improvement in nine (82%) cases and no change in two cases. Eight eyes (73%) measured 20/200 or better, with four of these eyes (36%) 20/80 or better. Final postoperative visual acuity ranged from 20/70 to light perception, with improvement in eight (73%) cases, no change in one case, and worsening in two cases. A statistically significant difference was found between preoperative and best postoperative visual acuity (P =.004) but not between preoperative and final visual acuity (P =.16). Hemorrhage recurred in three (27%) eyes, causing severe visual loss in one eye. This technique displaces submacular hemorrhage from the fovea and can improve vision in patients with age-related macular degeneration. However, recurrence of hemorrhage occurred in 27% of eyes and caused severe visual loss in one eye. A randomized, prospective clinical trial is necessary to determine the efficacy of this technique in comparison with other proposed treatments.
  • Article
    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. Prospective, noncomparative case series. 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. 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). Best and final postoperative visual acuity in relation to size and onset of hemorrhage, displacement of subretinal blood, and surgical complications. 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. 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.
  • Article
    No substantial recommendations exist regarding the management of anticoagulant drugs prior to ocular surgery. Stopping anticoagulation can cause fatal emboli, but sight-threatening bleeds may occur if anticoagulation is continued. We examined the effects of anticoagulation on vitreoretinal surgery. Clinical details were prospectively entered on a database. The anticoagulant status of 541 consecutive patients undergoing vitreoretinal surgery was recorded. Sixty patients in the study were taking aspirin and seven were taking warfarin. There were 11 cases of choroidal haemorrhage, one of which involved a warfarin user. Of 325 retinal detachment repairs, 21 (6.5%) had preoperative vitreous haemorrhages. Two of these patients were on aspirin and two were on warfarin. Sixty-six vitrectomies were performed for diabetic vitreous haemorrhages, of which nine re-bled postoperatively. One of these patients was taking warfarin. The association of warfarin with bleeding was statistically significant (relative risk 6.185). Anticoagulation had no effect on the number of significant perioperative (choroidal) haemorrhages. Aspirin had little effect on bleeding during vitreoretinal surgery. Warfarin, however, was associated with bleeding complications. We suggest that aspirin should not be stopped prior to surgery. Warfarin may be stopped if the patient's thromboembolic risk is low.
  • Article
    Full-text available
    We evaluated the safety and efficacy of intravitreous recombinant tissue plasminogen activator (rTPA) and gas for the treatment of submacular hemorrhage in age-related macular degeneration (ARMD). From January 2000 to April 2002, we enrolled 15 patients with submacular hemorrhage secondary to ARMD. All patients received 100 microg rTPA and 0.3 mL perfluoropropane intravitreously. Postoperatively, all patients were kept in a supine position for 4 hours followed by a face-down position for 4 days. Anatomic and functional results were evaluated during a follow-up period of 6 to 19 months. Submacular blood was completely displaced in 12 patients (80%) and partially in three (20%). Best postoperative visual acuity improved in all 15 eyes; in seven eyes (47%), the improvement was two or more lines. Final visual acuity improved in 12 eyes, remained stable in two eyes, and worsened in one eye. Onset of hemorrhage within 21 days was associated with better gains of lines in best postoperative (p = 0.0256) and final visual acuity (p = 0.044). Although two patients developed mild breakthrough vitreous hemorrhage within 1 day after treatment, no rTPA-related retinal toxicity was observed. Intravitreous injections of rTPA and gas are safe and effective in improving visual acuity in patients with submacular hemorrhage secondary to ARMD. Although the final visual outcome is often limited by the progression of the disease, significant and stable visual recovery over an extended follow-up period is possible using this easy and convenient technique.
  • Article
    Full-text available
    Aim: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes. Tenecteplase (25-350 micro g in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination. No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 micro g. At a dose of 150 micro g ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 micro g and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses. A dose of 50 micro g tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion.
  • Article
    Treatment of submacular hemorrhage with recombinant tissue plasminogen activator(rt-PA) and SF6 induces blood displacement out of the fovea by maintaining prone positioning. The underlying disease, e.g. the choroidal neovascularisation remains untreated. Nevertheless, it has been noted that the visual results of this method are more favorable than those expected in the natural course. Contributing long-term results the present study intends to give more information concerning this phenomenon. A total of 45 consecutive eyes were treated using a standardized procedure (duration of hemorrhage < or =1 week, area of hemorrhage 1-10 disc areas, 50 gammag rt-PA, 0.5 ml SF6 24 h later, prone positioning for 3 days). Those with a follow-up of > or =6 months were included in the study. From 25 patients a total of 25 eyes fulfilled the criteria. Postoperative visual acuity(3-7 days) was improved or unchanged in 19 eyes and worse in 6 eyes. Comparison of postoperative visual acuity after follow-up of an average of 14.2 months (range 6-28 months) revealed an improvement in 10 eyes, no change in 7 eyes and a deterioration in 8 eyes. A second treatment was performed in 2 eyes and photocoagulation in 1 eye. After more than 1 year the postoperative visual acuity was stable or even better in about two-thirds of the eyes therefore treatment with rt-PA and SF6 may also influence the choroidal neovascularisation.
  • Article
    To evaluate the anatomic and visual outcomes after a surgical procedure for displacement of thick submacular hemorrhage in patients with age-related macular degeneration. Retrospective, noncomparative, interventional case series. Twenty-nine consecutive eyes of 28 patients with thick submacular hemorrhage secondary to age-related macular degeneration. The procedure consisted of a pars plana vitrectomy with subretinal recombinant tissue plasminogen activator injection (125 micrograms/ml) through a translocation microcannula, followed by fluid-air exchange and postoperative prone positioning [correction]. Intraoperative and postoperative surgical complications, preoperative and postoperative best-corrected visual acuities, postoperative fluorescein angiography results, and additional postoperative treatments. Total subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement in the others. Based on fluorescein angiography results, 8 eyes were eligible for additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 lines of visual acuity, whereas 3 had lost more than 2 lines. The difference between preoperative and 3-month postoperative visual acuity was statistically significant (P = 0.0167). Complications consisted of 2 cases of vitreous hemorrhage that cleared within 4 weeks. This surgical technique seems useful in displacing thick submacular hemorrhage secondary to age-related macular degeneration, allowing postoperative fluorescein angiography testing and, potentially, subsequent treatments. No significant complication from the procedure was identified. However, further controlled studies will be required to assess its efficacy in the management of this difficult clinical problem.
  • Article
    To evaluate the prevalence of the most common serious adverse events associated with intravitreous (IVT) injection. A systematic search of the literature via PubMed from 1966 to March 1, 2004, was conducted to identify studies evaluating the safety of IVT injection. Data submitted in New Drug Applications to the U.S. Food and Drug Administration for drugs administered into the vitreous were included where available. Serious adverse events reported in each study were recorded, and risk per eye and risk per injection were calculated for the following serious adverse events: endophthalmitis, retinal detachment, iritis/uveitis, intraocular hemorrhage, ocular hypertension, cataract, and hypotony. Rare complications also were noted. Data from 14,866 IVT injections in 4,382 eyes were analyzed. There were 38 cases of endophthalmitis (including those reported as pseudoendophthalmitis) for a prevalence of 0.3% per injection and 0.9% per eye. Excluding cases reported specifically as pseudoendophthalmitis, the prevalence of endophthalmitis was 0.2% per injection and 0.5% per eye. Retinal detachment, iritis/uveitis, ocular hypertension, cataract, intraocular hemorrhage, and hypotony were generally associated with IVT injection of specific compounds and were infrequently attributed by the investigators to the injection procedure itself. Retinal vascular occlusions were described rarely in patients after IVT injection, and it was unclear in most cases whether these represented true injection-related complications or chance associations. The risk of serious adverse events reported after IVT injection is low. Nevertheless, careful attention to injection technique and appropriate postinjection monitoring are essential because uncommon injection-related complications may be associated with permanent vision loss.
  • Article
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    Past, present, and future The systemic (intravenous) administration of genetically modified (recombinant) tissue plasminogen activator (tPA) for thrombolysis in coronary arteries was approved by the US Federal Drug Administration in 1988. Since then, use of this approved drug has been extended to many non-approved indications, especially in the eye.1 Tissue plasminogen activator is a naturally occurring serine protease produced by a variety of mammalian tissues, especially endothelial cells. Ocular tissues that contain tPA include the conjunctiva, cornea, trabecular meshwork, lens, vitreous, and retina.1–3 In normal adult human eyes, the aqueous humour contains a significant amount of tPA that is some 30 times more than in plasma.4 The major enzymatic action of tPA is the conversion of plasminogen (a zymogen) into plasmin, an active serine protease that hydrolyses fibrin. Compared to other fibrinolytic agents (for example, urokinase and streptokinase), tPA has several advantages: fibrin forms a ternary complex with tPA and plasminogen, which increases the rate of plasminogen activation several hundred-fold; in addition, tPA serves to protect plasmin from antiplasmin inhibitors until complete clot lysis is achieved.5–7 Even though cost effective, urokinase and streptokinase did not …