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Ophthalmology. Retina Apr 2020To evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical tissue-derived cells (palucorcel) via a novel delivery system in patients with geographic atrophy (GA).
DESIGN
Multicenter, open-label phase 2b study.
PARTICIPANTS
Participants were 55 to 90 years with GA secondary to age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) of 20/80 to 20/800. Exclusion criteria included neovascular AMD in the intervention eye, glaucoma with intraocular pressure of 25 mmHg or more, or other significant ophthalmologic conditions.
METHODS
Participants received a subretinal injection of palucorcel, 3.0 × 10 cells in 50 μl, using the custom-designed delivery system and surgical procedure.
MAIN OUTCOME MEASURES
Safety assessments included treatment-emergent adverse events (AEs), immunologic assessments, and ophthalmologic evaluations. Efficacy was evaluated as change in mean number of BCVA letters from baseline, proportion of participants gaining 15 BCVA letters or more, and growth rate of GA lesions at 12 months.
RESULTS
Surgery and palucorcel administration were performed in 21 participants at 8 sites by 8 different surgeons. At baseline, median total area of GA was 13.4 mm and median BCVA was 43 letters in the intervention eye. Eye-related AEs occurred in 76% of participants (16/21), including conjunctival hemorrhage (n = 5), retinal hemorrhage (n = 4), and vitreous floaters (n = 4). Most AEs were mild and resolved within 1 month. No serious AEs, no retinal detachment or perforation, and no significant changes in intraocular pressure occurred. At month 12, mean change in BCVA from baseline was -5.9 letters correct (standard deviation, 13.0 letters correct) in the intervention eye and -3.7 letters correct (standard deviation, 9.0 letters correct) in the fellow eye. No participants showed improvement of 15 letters or more in the intervention eye, and 3 participants lost more than 15 letters by month 1. No apparent effect of treatment was observed.
CONCLUSIONS
Palucorcel was delivered successfully to the targeted subretinal site using a novel delivery system and suprachoroidal approach for most participants; however, improvement in GA area, retardation of growth, or visual acuity were not demonstrated.
Topics: Cell- and Tissue-Based Therapy; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Geographic Atrophy; Humans; Injections, Intraocular; Macula Lutea; Retina; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Wet Macular Degeneration
PubMed: 32033908
DOI: 10.1016/j.oret.2019.11.011 -
International Journal of Retina and... 2020To objectively evaluate YAG laser vitreolysis for symptomatic vitreous floaters using color photo imaging.
BACKGROUND
To objectively evaluate YAG laser vitreolysis for symptomatic vitreous floaters using color photo imaging.
METHODS
In this interventional and prospective study, 32 eyes of 32 patients with symptomatic vitreous floaters secondary to posterior vitreous detachment (PVD) were treated with a single session of yttrium aluminum garnet (YAG) laser. Primary outcomes were objective and subjective changes measured by masked grading of color fundus photographs and National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25), respectively. Secondary outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA) and adverse events. Wilcoxon signed-rank test was used to analyze the results of the objective and subjective assessments at each time point. P < 0.05 was considered statistically significant.
RESULTS
Thirty-two patients (32 eyes; 13 men and 19 women) with symptomatic vitreous floaters were enrolled in this study (mean age: 59.4 years). All study patients were followed up for 6 months. Following the laser vitreolysis, there was a statistically significant improvement in both the near visual function (z = - 2.97; p = 0.003; r = 0.633) and visual disturbance rate (z = - 3.97; p < 0.001; r = 0.84). Distance visual function did not show statistically significant difference after the laser procedure (p = 1.00). Color fundus photograph did reveal vitreous opacity improvement over time in 93.7% of study eyes (partial improvement in 37.5% and total improvement in 56.2% of study eyes). During the follow-up period, recurrence of vitreous floaters, BCVA deterioration and adverse events were not observed.
CONCLUSIONS
YAG laser vitreolysis decreased the amount of vitreous floaters opacities seen on color fundus imaging and improved related symptoms according to the NEI VFQ-25 responses.
PubMed: 31988795
DOI: 10.1186/s40942-019-0205-8 -
Severe intraocular lens opacification after scleral suturing in a patient with retinitis pigmentosa.Romanian Journal of Ophthalmology 2019To report a case of late intraocular lens (IOL) opacification after scleral suturing in a patient with retinitis pigmentosa. A 36-year-old man presented with visual...
To report a case of late intraocular lens (IOL) opacification after scleral suturing in a patient with retinitis pigmentosa. A 36-year-old man presented with visual impairment increasing gradually over the preceding three months. Seven years earlier, he underwent bilateral phacoemulsification cataract surgery with implantation of a Rayner 620H IOL in the left eye, and a Quatrix P12 IOL in the right eye. Five months prior to admission, scleral suturing of the subluxated IOL in the left eye was performed due to subluxation. Slit lamp examination revealed significant opacities within the IOL and marked vitreous floaters in the left eye. The previous diagnosis of retinitis pigmentosa and rotary nystagmus were confirmed. Subsequently, he underwent 25-gauge vitrectomy with IOL removal in his left eye. Light microscopy of the explanted IOL revealed unevenly distributed microvacuoles. Subsequently, vitrectomy with IOL removal was performed after 3 months in the right eye. The patient had a good recovery of vision, with a visual acuity of 20/200 in both eyes with contact lenses. The presented case demonstrated a significant increase in IOL opacification following scleral suturing. The presumed pathogenesis includes IOL microdeformation with development of IOL matrix cavities and intense inflammatory response related to scleral suturing.
Topics: Adult; Cataract; Device Removal; Humans; Lens Implantation, Intraocular; Lenses, Intraocular; Male; Phacoemulsification; Postoperative Complications; Prosthesis Failure; Reoperation; Retinitis Pigmentosa; Sclera; Suture Techniques; Visual Acuity; Vitrectomy
PubMed: 31915739
DOI: No ID Found -
[Zhonghua Yan Ke Za Zhi] Chinese... Oct 2019To identify differentially expressed proteins between the patients with proliferative diabetic retinopathy (PDR) and vitreous floaters, and explore treatment target for...
To identify differentially expressed proteins between the patients with proliferative diabetic retinopathy (PDR) and vitreous floaters, and explore treatment target for PDR based on isobaric tags for relative and absolute quantification (iTRAQ) LC-MS/MS Proteomics. Vitreous samples were collected from 28 eyes of patients with PDR and 4 eyes with vitreous floaters, which served as controls. For quantitative proteomics, vitreous samples were combined and proteins extracted and labeled with iTRAQ peptide-tagging reagents. Samples were fractionated by liquid chromatography (LC), analyzed by tandem mass spectrometry (MS/MS) and Gene Ontology (GO) analyses performed on differentially expressed proteins identified in the PDR samples. In the PDR vitreous, 26 proteins were identified that were differentially expressed when compared to the controls. Of these, 7 showed a significant increase (0.05) and 19 a significant decrease (0.05)in expression in PDR patients. These included some high abundance proteins including Retinoic acid receptor reactive protein 2 (PDR 1=85.0, PDR 2=83.0, Control 1=119.6, Control 2=120.2, FC=0.710, 0.001), Semaphorin-4B(PDR 1=64.4, PDR 2=68.8, Control 1=135.4, Control 2=146.0, FC=0.473, 0.023), Apolipoprotein B (PDR 1=104.4, PDR 2=106.6, Control 1=89.0, Control 2=85.3, FC=1.211, 0.024), and Heat shock protein 70 (PDR 1=69.3, PDR 2=75.0, Control 1=137.7, Control 2=138.3, FC=0.523, 0.026), which are closely related to the pathological mechanism of PDR. GO analysis clustered the differentially expressed genes into three major functional domains: Biological Processes, Molecular Function and Cellular Component. Differential gene expression was found in the categories of cellular metabolism, organonitrogen compound and carbohydrate derivative metabolic processes, transferase activity and transmembrane signaling receptor activity. KEGG Pathway analysis indicate that Chemerin signaling through Akt, Sema4B signaling via PI3K, and HIF-1α signal pathways were all altered in the PDR samples. In this study we identified variations in expression of genes extensively involved in key biological processes in the retina including neovascularization, cellular metabolism and transmembrane signaling, which provide new insights into the pathophysiology of PDR. Extracellular matrix was degraded and endothelial cell migration was induced by Chemerin, in addition, the destruction of blood-retinal barrier and neuronal apoptosis were induced by ApoB. Chemerin and ApoB accelerated the development of PDR. Sema 4B participated in vascular protection, HSP70 conducted anti-apoptosis. These two cytokines protected the retinal neurovascular in PDR patients. Therefore, Chemerin, Sema 4B, ApoB and HSP70 may be the treatment target for PDR. .
Topics: Biomarkers; Case-Control Studies; Chemokines; Chromatography, Liquid; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Humans; Intercellular Signaling Peptides and Proteins; Proteome; Proteomics; Tandem Mass Spectrometry; Vitreous Body
PubMed: 31607066
DOI: 10.3760/cma.j.issn.0412-4081.2019.10.008 -
Neurophotonics Oct 2019Age-related macular degeneration (AMD) is a vision-threatening disease that affects the outer retina and choroid of elderly adults. Because photoreceptors are found in...
Age-related macular degeneration (AMD) is a vision-threatening disease that affects the outer retina and choroid of elderly adults. Because photoreceptors are found in the outer retina and rely primarily on the trophic support of the underlying choriocapillaris, imaging of flow or lack thereof in choriocapillaris by optical coherence tomography angiography (OCTA) has great clinical potential in AMD assessment. We introduce a metric using OCTA, named "focal perfusion loss" (FPL) to describe the effects of age and non-neovascular AMD on choriocapillaris flow. Because OCTA imaging of choriocapillaris is vulnerable to artifacts-namely motion, projections, segmentation errors, and shadows-they are removed by postprocessing software. The shadow detection software is a machine learning algorithm recently developed for the evaluation of the retinal circulation and here adapted for choriocapillaris analysis. It aims to exclude areas with unreliable flow signal due to blocking of the OCT beam by objects anterior to the choriocapillaris (e.g., drusen, retinal vessels, vitreous floaters, and iris). We found that both the FPL and the capillary density were able to detect changes in the choriocapillaris of AMD and healthy age-matched subjects with respect to young controls. The dominant cause of shadowing in AMD is drusen, and the shadow exclusion algorithm helps determine which areas under drusen retain sufficient signal for perfusion evaluation and which areas must be excluded. Such analysis allowed us to determine unambiguously that choriocapillaris density under drusen is indeed reduced.
PubMed: 31528658
DOI: 10.1117/1.NPh.6.4.041108 -
Ophthalmology Nov 2019Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome... (Comparative Study)
Comparative Study
PURPOSE
Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision.
DESIGN
Retrospective, comparative study.
PARTICIPANTS
One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation.
METHODS
The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision.
MAIN OUTCOME MEASURES
Results of NEI-VFQ-39, QUS, BCVA, and CSF.
RESULTS
Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P < 0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P < 0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings.
CONCLUSIONS
As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.
Topics: Adult; Aged; Contrast Sensitivity; Eye Diseases; Female; Humans; Lasers, Solid-State; Male; Middle Aged; Ophthalmoscopy; Patient Satisfaction; Retrospective Studies; Sickness Impact Profile; Surveys and Questionnaires; Ultrasonography; Visual Acuity; Vitrectomy; Vitreous Body
PubMed: 31471088
DOI: 10.1016/j.ophtha.2019.06.021 -
Biomedical Optics Express Jul 2019The capillary nonperfusion area (NPA) is a key quantifiable biomarker in the evaluation of diabetic retinopathy (DR) using optical coherence tomography angiography...
The capillary nonperfusion area (NPA) is a key quantifiable biomarker in the evaluation of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). However, signal reduction artifacts caused by vitreous floaters, pupil vignetting, or defocus present significant obstacles to accurate quantification. We have developed a convolutional neural network, MEDnet-V2, to distinguish NPA from signal reduction artifacts in 6×6 mm OCTA. The network achieves strong specificity and sensitivity for NPA detection across a wide range of DR severity and scan quality.
PubMed: 31360599
DOI: 10.1364/BOE.10.003257 -
ACS Nano Jul 2019Myopia, diabetes, and aging are the main causes of progressive vitreous collagen aggregation, resulting in vitreous opacities, which can significantly disturb vision. As...
Myopia, diabetes, and aging are the main causes of progressive vitreous collagen aggregation, resulting in vitreous opacities, which can significantly disturb vision. As vitreous opacities, which induce the visual phenomenon of "floaters", are accessible with nanomaterials and light, we propose a nanotechnology-based approach to locally ablate them with highly reduced light energy compared to the more traditional YAG laser therapy. Our strategy relies on the plasmon properties of gold nanoparticles that generate vapor nanobubbles upon pulsed-laser illumination whose mechanical force can ablate vitreous opacities. We designed gold nanoparticles coated with hyaluronic acid (HA), which have excellent diffusional mobility in human vitreous, an essential requirement to reach the vitreous opacities. In addition, we found that HA-coated gold nanoparticles can accumulate extensively on human vitreous opacities that were obtained by vitrectomy from patients with vision-degrading myodesopsia. When subsequently applying nanosecond laser pulses, the collagen aggregates were efficiently destroyed with ∼1000 times less light energy than typically used in YAG laser therapy. This low-energy "floater-specific destruction", which is due to the accumulation of the small gold nanoparticles on the opacities, is attractive, as it may be safer to the surrounding ocular tissues while at the same time being easier and faster to apply compared to YAG laser therapy, where the opacities need to be ablated piece by piece by a tightly focused laser beam. Gold nanoparticle-assisted photoablation may therefore provide a safer, faster, and more reliable destruction of vitreous opacities in the treatment of ophthalmologic diseases.
Topics: Aged, 80 and over; Animals; Cattle; Cell Survival; Cells, Cultured; Gold; Humans; Hyaluronic Acid; Light; Metal Nanoparticles; Nanotechnology; Particle Size; Photochemical Processes; Rats; Surface Properties; Vitrectomy; Vitreous Body; Volatilization
PubMed: 31287662
DOI: 10.1021/acsnano.9b04050 -
Journal of Pediatric Ophthalmology and... Jul 2019A patient treated for retinoblastoma developed vitreous floaters 15 years later and was referred for recurrence with vitreous seeding. Clinical examination demonstrated...
A patient treated for retinoblastoma developed vitreous floaters 15 years later and was referred for recurrence with vitreous seeding. Clinical examination demonstrated a regressed scar and numerous calcified vitreous opacities with a "clear zone" on ultrasonography. The final diagnosis was asteroid hyalosis in an eye with regressed retinoblastoma. [J Pediatr Ophthalmol Strabismus. 2019;56:e41-e44.].
Topics: Adult; Diagnosis, Differential; Eye Diseases; Humans; Male; Retinal Neoplasms; Retinoblastoma; Tomography, Optical Coherence; Ultrasonography; Vitreous Body
PubMed: 31282959
DOI: 10.3928/01913913-20190515-01 -
Ophthalmology. Retina Jul 2019
Re: Thompson: Much Ado about Nothing (or Something)-What Is the Role of Vitrectomy and Yttrium-Aluminum-Garnet Laser for Vitreous Floaters? (Ophthalmol Retina. 2018;2:879-880).
PubMed: 31277804
DOI: 10.1016/j.oret.2019.01.025