9 research outputs found
Assessment of Ischemic Index in Retinal Vascular Diseases Using Ultra-Wide-Field Fluorescein Angiography:Single Versus Summarized Image
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Retinal toxicity of commercially available intravitreal ketorolac in albino rabbits
To determine whether intravitreal injection of a commercially available ketorolac tromethamine preparation causes retinal toxicity in albino rabbits.
Nine albino rabbits were injected intravitreally with ketorolac tromethamine (3 mg; 0.1 mL) in one eye and saline (0.1 mL) in the fellow eye. Six of the rabbits received a single injection of ketorolac, and the other three rabbits underwent biweekly injection for a total of four injections. Electroretinography testing was performed on both eyes at different time intervals during 4 weeks of follow-up in the single injection group, and during 12 weeks of follow-up in the multiple injection group. Visual evoked potentials were recorded from each rabbit using monocular and binocular stimulation at the end of the follow-up period. Animals were then killed, and the retinas were prepared for morphologic examination at the light microscope level and for immunostaining for glial fibrillary acidic protein, as a marker of retinal damage.
The electroretinography responses from the control and experimental eyes were similar throughout the follow-up period in all rabbits of both experimental groups. There were no differences in the flash visual evoked potential responses between experimental and control eyes in the single injection group, while in the repeated injection group, statistically significant differences were found. Light microscopy did not identify significant histologic differences between the retinas from control and experimental eyes after a single dose. However, after repeated dosing, two of three eyes showed histologic evidence of local toxicity. Immunocytochemical analysis showed no glial fibrillary acidic protein staining in Muller (glial) cells throughout the retina in the single injection group. Slight glial fibrillary acidic protein staining was detected in only one of the three retinas from rabbits in the repeated injection group.
Commercially available ketorolac tromethamine was found to be toxic to the retinas of albino rabbits following multiple intravitreal injections at a dose of 3 mg while no electrophysiologic toxicity was found. Therefore, the use of commercially available ketorolac containing alcohol, for intravitreal injection is not recommended
Structural Confirmation of Lymphatic Outflow from Subconjunctival Blebs of Live Human Subjects.
PURPOSE: To uncover the mechanism of subconjunctival outflow in human patients. DESIGN: Cross-sectional study. SUBJECTS/PARTICIPANTS AND/OR CONTROLS: Fifteen subjects receiving subconjunctival anesthesia prior to intravitreal injection for routine clinical care. METHODS: Anterior segment OCT (AS-OCT) was performed in patients with various instances of conjunctival edema or subconjunctival fluid. Other subjects received a subconjunctival mixture of 0.005% indocyanine green and 2% lidocaine. After subconjunctival injection of the tracer/anesthetic mixture, blebs and associated outflow pathways were angiographically imaged and the time for appearance recorded. The pattern and structure of outflow pathways were studied using AS-OCT. Angiographic and AS-OCT results were compared to trabecular/conventional outflow imaging which demonstrates veins. MAIN OUTCOME MEASURES: Ocular surface lymphangiography and AS-OCT images. RESULTS: AS-OCT of the conjunctiva in a normal eye demonstrated thin non-edematous conjunctiva with absent intraconjunctival lumens or subconjunctival fluid. Subjects with a history of trabeculectomy, subconjunctival drug injection, or chemosis demonstrated thickened conjunctiva and intraconjunctival luminal pathways that contained valve-like structures. Tracer-based studies in patients demonstrated blebs with irregular subconjunctival bleb-related outflow patterns that arose in a time-dependent fashion. These angiographic pathways were luminal on OCT, sausage-shaped, and contained intraluminal valve-like structures. This was in contrast to trabecular/conventional outflow imaging where pathways were classically Y-shaped, of even-caliber, and lacked valve-like structures. DISCUSSION: Outflow pathways were seen in cases of conjunctival edema and after subconjunctival tracer injection. These pathways were lymphatic based upon pattern and structural study. Better understanding of bleb-related lymphatic outflow may lead to improved bleb-requiring glaucoma surgeries and subconjunctival drug delivery
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ISCHEMIC INDEX AND NEOVASCULARIZATION IN CENTRAL RETINAL VEIN OCCLUSION
Purpose: To explore the association of angiographic nonperfusion with anterior segment and posterior segment neovascularization in central retinal vein occlusion (CRVO).
Methods: An imaging database at one institution was searched for the diagnosis of central retinal vein occlusion. Ultra wide field fluorescein angiograms were graded for image quality, the presence of retinal neovascularization, and the quantity of nonperfusion; an ischemic index (ISI) was calculated. Charts were reviewed to exclude eyes with previous treatment and to determine which eyes had anterior segment or posterior segment neovascularization on the day of the angiogram. Time from onset to presentation could not accurately be ascertained.
Results: In a 39-month period, there were 69 eyes that met inclusion criteria. The mean ISI was 25% (SD, 26%; range, 0-100%), and 15 eyes (21%) with neovascularization had a mean ISI of 75% (range, 47-100%) compared with eyes without neovascularization that had an ISI of 6% (range, 0-43%). Ischemic index significantly correlated to neovascularization, and eyes that had evidence of neovascularization had an ISI >45% (P < 0.0001).
Conclusion: Ultra wide field fluorescein angiography provides visualization of nonperfusion in eyes with central retinal vein occlusion. Eyes with neovascularization on the day of the angiogram were found to have significantly larger areas of retinal nonperfusion compared with eyes without neovascularization. A prospective study is indicated to know if early treatment of peripheral retinal nonperfusion in CRVO improves outcomes. RETINA 31:105-110, 201
Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset
International audiencePurpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON).Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial.Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included.Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye.Main outcome measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4-treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96.Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4-treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4-treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from -0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4-treated and sham-treated eyes was -0.01 logMAR (P = 0.89); the primary end point of a -0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4-treated and sham-treated eyes, respectively.Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes