To establish the safety, tolerability, pharmacokinetics, and pharmacodynamics of an intravitreal injection of recombinant human complement factor H (CFH), GEM103, in individuals with genetically ...defined age-related macular degeneration (AMD) and geographic atrophy (GA).
Phase I single ascending-dose, open-label clinical trial (ClinicalTrials.gov identifier, NCT04246866).
Twelve individuals 50 years of age or older with a confirmed diagnosis of foveal GA in the study eye.
Participants were assigned to the increasing dose cohorts and received 1 50-μl intravitreal injection of GEM103 at doses of 50 μg/eye, 100 μg/eye, 250 μg/eye, or 500 μg/eye; dose escalation was dependent on the occurrence of dose-limiting toxicities.
Safety assessments included ocular and systemic adverse events (AEs), ocular examinations, clinical laboratory and vital signs, and serum antidrug antibody levels. Biomarkers, measured in the aqueous humor (AH), included CFH and complement activation biomarkers factor Ba and complement component 3a.
No dose-limiting toxicities were reported, enabling escalation to the maximum study dose. No anti-GEM103 antidrug antibodies were detected during the study. Four participants experienced AEs; these were nonserious, mild or moderate in severity, and unrelated to GEM103. The AEs in 2 of these participants were related to the intravitreal injection procedure. No clinically significant ophthalmic changes and no ocular inflammation were observed. Visual acuity was maintained and stable throughout the 8-week follow-up period. No choroidal neovascularization occurred. CFH levels increased in a dose-dependent manner after GEM103 administration with supraphysiological levels observed at week 1; levels were more than baseline for 8 weeks or more in all participants receiving single doses of 100 μg or more. Complement activation biomarkers were reduced 7 days after dose administration.
A single intravitreal administration of GEM103 (up to 500 μg/eye) was well tolerated in individuals with GA. Of the few mild or moderate AEs reported, none were determined to be related to GEM103. No intraocular inflammation or choroidal neovascularization developed. CFH levels in AH were increased and stable for 8 weeks, with pharmacodynamic data suggesting that GEM103 restored complement regulation. These results support further development in a repeat-dose trial in patients with GA with AMD.
Assessment of biological effect, visual acuity changes, and safety of intravitreal (IVT) ranibizumab in patients with macular edema associated with perfused central retinal vein occlusion (CRVO).
...Ongoing, prospective, open-label, single-center, uncontrolled study.
Ten adult patients with macular edema associated with perfused CRVO.
Patients were randomly assigned to receive 3 monthly IVT injections of either 0.3 or 0.5 mg ranibizumab (n = 5 at each dose). Additional injections were administered quarterly as needed over the ensuing 21 months at the physician's discretion for recurrent or persistent macular edema.
The predetermined primary endpoint was the percentage of patients gaining >or=15 letters of best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity (BCVA). The secondary endpoints include the mean change in BCVA and central retinal thickness (CRT) measured by optical coherence tomography, the rate of progression to ischemic CRVO, extent of intraocular hemorrhage, retinal vein diameter, optic nerve head swelling, and the incidence and severity of ocular and nonocular adverse events.
After 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients, respectively, gained >or=15 letters in BCVA; mean BCVA improved by 12+/-20 letters, 3+/-21 letters, and 1+/-24 letters, respectively, compared with baseline; CRT showed a mean decrease of 272+/-244 microm, 88+/-178 microm, and 119+/-153 microm, compared with baseline. No significant differences were observed between the 0.3- and 0.5-mg doses. Most patients experienced decreases in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head swelling at months 3 and 6 compared with baseline. No patients progressed to ischemic CRVO or experienced a severe adverse event that was attributed to ranibizumab.
Ranibizumab is generally well-tolerated and may improve BCVA and decrease CRT. The improvements in BCVA and CRT observed during the initial monthly injection period (0 to 3 months) were possibly lost to the recurrence of macular edema in between ranibizumab injection during the quarterly treatments (3 to 9 months). The extent of retinal hemorrhage, retinal vein diameter, and nerve swelling continued to normalize for most of the patients from baseline to 6 months. Follow-up is ongoing, and alternative dosing regimens are being evaluated.
Vitreoretinal trauma Pieramici, Dante J
Ophthalmology clinics of North America
15, Številka:
2
Journal Article
During the last two decades, vitreous surgical techniques have become more refined, so it is now unusual that an eye cannot be saved, even following very severe ocular injury. This article reviews ...some of the more recent advances in the understanding and management of posterior segment complications of mechanical injury.
To quantitatively measure the effects of caffeine and propranolol, a nonselective beta-blocking agent, on surgeon hand tremor during simulated vitreoretinal microsurgery.
Seventeen ophthalmic ...surgeons were tested on 3 separate days. On each day, subjects ingested 200 mg of caffeine, 10 mg of propranolol hydrochloride, or gelatin placebo. The drugs were administered as part of a double-masked, placebo-controlled trial. Hand tremor was measured using the Microsurgery Advanced Design Laboratory Stability, Activation, and Maneuverability tester (MADSAM), a high-resolution, noncontact position tracking system.
The average percent magnitude changes from baseline tremor measurements were +15%, +31%, and -22% for placebo, caffeine, and propranolol groups, respectively. Analysis of variance techniques accounting for effects of individuals, drugs, and day order demonstrated that only drug effects on percent magnitude change of tremor were statistically significant (P = .01, F test). Detailed comparisons of the 2 drug groups with the placebo group revealed that, after adjusting for individual and order effects, only the mean decrease in tremor due to ingestion of propranolol was a statistically significant trend (P = .03, F test). Although caffeine caused a larger mean increase in percent magnitude change in tremor than placebo, this trend was not statistically significant (P = .34, F test). The evaluation of systemic physiologic measurements showed that there were statistically significant drug effects on percent change in systolic (P < .001, F test) and diastolic (P = .002, F test) blood pressure and pulse rate (P = .002, F test). Individual and day order effects were not significant. No adverse side effects were observed or reported in our test subjects.
Physiologic surgeon hand tremor can be decreased by the oral intake of a low dose of propranolol.
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world. Most of the severe vision loss associated with AMD is due to the development of choroidal ...neovascularization (CNV). The specific causes of AMD and in particular, its neovascular phase, remain uncertain. During the past two decades a number of large prospective clinical trials, observational epidemiologic studies, and population-based cohort studies have furthered our understanding of this blinding ocular condition. The Macular Photocoagulation Study has received praise for its many contributions in the laser treatment of neovascular complications of AMD; however, these trials have made other significant contributions by helping to better define the natural history of AMD, and in particular, risk factors for the development of CNV in eyes with non-neovascular disease. This type of information may provide significant clues for researchers regarding disease pathogenesis and identify a high-risk group in whom to target new treatment strategies. For patients currently diagnosed with macular degeneration, this information can lead to a better understanding of their condition and a more accurate prognosis of their ocular health and vision status. This article reviews information from a variety of sources to investigate incidence rates and risk factors for the development of CNV in the fellow eye of patients with AMD and unilateral neovascular maculopathy.
Significant anterior segment complications can occur following periocular or intraocular injections. These complications may be intraoperative or postoperative. They vary with different procedures ...and may be secondary to the surgical procedure or related to drug toxicity. Cataract and increased intraocular pressure are the most frequent complications. Other less commonly reported complications include hypotony, hyphema, corneal decompensation, strabismus, and cosmetic complications.
When confronted with the ocular trauma patient, the initial evaluation always begins with the assessment of the patient. Once it has been determined that the patient is stable, and other serious ...nonocular injuries have been addressed, a thorough medical/surgical history is taken followed by a more focused ocular history. Key elements include prior surgery, trauma, and any previously existing eye disease. A full examination is carried out in a methodical and rational fashion, beginning with gross external inspection. Visual acuity is measured in each eye independently. Optic nerve function is assessed by testing for a relative afferent pupillary defect, performing gross confrontational visual field testing, identifying any relative difference in subjective brightness perception, and checking color vision. If appropriate, the IOP is measured and a careful slit lamp examination is performed, combined with dilated indirect ophthalmoscopy. Obvious open globe injury can often be appreciated with a simple penlight examination. Uncooperative patients should be examined under anesthesia in a controlled, monitored setting involving experienced critical care personnel. Additional information may be obtained utilizing ancillary testing (primarily CT and ultrasonography). If the combination of clinical findings and ancillary testing is still not definitive, then formal exploration under anesthesia in the operating room in recommended. Photodocumentation is recommended whenever feasible. Figs. 1-14 provide an overview of many of the points stressed above.
To determine the safety and efficacy of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.
Multicenter, randomized, double-masked, placebo-controlled clinical trial.
A total ...of 51 patients participated in this trial (power = 36%, 2-tailed test).
Patients presenting with traumatic hyphema were randomly assigned to 5-day treatment with topical aminocaproic acid or a placebo gel. Patients were monitored daily with ocular examination and vital sign testing for the 5 days of treatment and at 24 and 48 hours after treatment. General physical examination and laboratory testing were performed at baseline and day 5.
The main efficacy variable was the rate of rebleeding. Secondary efficacy variables included time to hyphema clearance, intraocular pressure, time to secondary hemorrhage, and visual acuity. Safety variables included adverse events, vital signs, and laboratory measurements.
Rebleeding occurred in 30% of the placebo group (8 of 27; 95% confidence interval CI = 14–50%), versus 8% of the treatment group (2 of 24; 95% CI = 1–27%), for an estimated continuity-corrected difference in percentage of patients with bleeding of 17% (95% CI = −3–38%). Secondary efficacy variables were similar in the groups, except that there was a trend towards more visual improvement in the topical aminocaproic acid group (54%) than in the placebo group (30%) at the last measurement (
P = 0.08). Adverse events were similar.
This study provides evidence that topical aminocaproic acid is safe and demonstrates trends towards reducing the rebleeding rate in the management of traumatic hyphema. However, because the study was terminated before complete enrollment, more definitive recommendations will require a larger trial.
