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1.
Retina ; 44(6): 1083-1091, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38308567

ABSTRACT

PURPOSE: To investigate the imaging and clinical features of polypoidal choroidal vasculopathy (PCV) with pulsation. METHODS: The PCV eyes were classified into pulsatile and nonpulsatile PCV groups according to the pulsation on indocyanine green angiography. Imaging features including the dye filling time of the polyp and clinical features were compared. RESULTS: A total of 75 eyes were classified into the pulsatile PCV (30 eyes) and the nonpulsatile PCV (45 eyes) groups. The initial filling time and complete filling time of the polyp of the pulsatile PCV group (2.59 ± 0.93 and 8.33 ± 3.42 seconds) were shorter than those of the nonpulsatile PCV group (4.11 ± 1.87 and 10.63 ± 3.81 seconds, P < 0.001 and P = 0.010, respectively). The pigment epithelial detachment height of the pulsatile PCV group (414.90 ± 377.15 µ m) was greater than that of the nonpulsatile PCV group (247.81 ± 164.07 µ m, P = 0.030). The pulsatile PCV group showed a higher prevalence of subretinal hemorrhage (43.33%) after intravitreal injection than the nonpulsatile PCV group (13.95%, P = 0.005) during 12 months. The mean number of injections during 12 months of the pulsatile PCV group (5.48 ± 1.46) was greater than that of the nonpulsatile PCV group (4.09 ± 1.21, P < 0.001). CONCLUSION: Eyes with pulsatile PCV showed shorter filling time of the polyp, greater pigment epithelial detachment height, higher prevalence of subretinal hemorrhage, and more intravitreal injection numbers during 12 months. These might suggest that PCV has distinct imaging and clinical features according to the polyp pulsation.


Subject(s)
Choroid , Fluorescein Angiography , Polyps , Tomography, Optical Coherence , Humans , Female , Fluorescein Angiography/methods , Male , Aged , Polyps/diagnosis , Polyps/physiopathology , Choroid/blood supply , Tomography, Optical Coherence/methods , Retrospective Studies , Middle Aged , Visual Acuity/physiology , Fundus Oculi , Indocyanine Green/administration & dosage , Coloring Agents/administration & dosage , Choroid Diseases/diagnosis , Choroid Diseases/physiopathology , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/physiopathology , Choroidal Neovascularization/drug therapy , Aged, 80 and over , Intravitreal Injections , Polypoidal Choroidal Vasculopathy
2.
J Craniofac Surg ; 35(1): e32-e34, 2024.
Article in English | MEDLINE | ID: mdl-37702519

ABSTRACT

Polyglactin 910 (Vicryl) and polypropylene (Prolene) are common suture materials used in ophthalmic surgical procedures. However, there are limited studies assessing tissue reactions to different sutures in eyelid areas. In this study, these suture materials were used subcutaneously in 10 lateral canthi of 5 pigs. Clinical reactive score (CRS) was assessed 14 days and 60 days after surgery. On histology, subcutaneous tissue reactions were assessed by the presence of different inflammatory cells, and the aggregate tissue irritation score was calculated. CRS and the histology score did not differ between these sutures. None of the suture materials used were superior for use in the lateral canthi of pig eyes. Therefore, we recommend both of these sutures for use in the subcutaneous tissue of the eyelid area in animal experiments or clinical practice.


Subject(s)
Lacrimal Apparatus , Research Design , Swine , Animals , Sutures , Polyglactin 910 , Eyelids/surgery , Suture Techniques
3.
Graefes Arch Clin Exp Ophthalmol ; 262(5): 1465-1474, 2024 May.
Article in English | MEDLINE | ID: mdl-38117309

ABSTRACT

PURPOSE: To evaluate anatomical changes in the low-stage partial attachment-type idiopathic epiretinal membrane (iERM) over 2 years. METHODS: Data from patients with low-stage partial attachment-type iERM (stage 2) were analyzed. The main outcome measures were anatomical changes, including changes in the foveal avascular zone (FAZ) area, vessel density (VD) in the vascular plexus, and thickness of retinal sublayers during the follow-up period. RESULTS: Thirty patients (mean age: 68±12 years) were included in the study. The FAZ area on the superficial vascular plexus (SVP) significantly decreased from baseline (0.12±0.08 mm2) to month 24 (0.10±0.08 mm2, p=0.024). However, the FAZ area on the deep vascular plexus (DVP) did not significantly decrease from baseline (0.15±0.13 mm2) to month 24 (0.14±0.14 mm2, p=0.099). VDs on both the SVP and DVP did not show significant change from baseline (29.51±8.14% vs. 28.35±5.63%) to month 24 (29.79±9.77%, p=0.564 vs. 28.17±5.75%, p=0.417). Parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness decreased from baseline (108.77±13.61 µm) to month 24 (103.03±15.54 µm, p=0.004). The central total retinal layer thickness did not significantly change from baseline (396.07±64.86 µm) to month 24 (392.04±72.72 µm, p=0.570). CONCLUSION: Even in low-stage ERM, inner retinal changes, including GCIPL thickness, occurred during follow-up periods, which might be owing to degenerative changes or centrifugal movement.


Subject(s)
Epiretinal Membrane , Humans , Middle Aged , Aged , Aged, 80 and over , Epiretinal Membrane/diagnosis , Fluorescein Angiography/methods , Retinal Vessels , Fovea Centralis/blood supply , Follow-Up Studies , Tomography, Optical Coherence/methods , Retrospective Studies
4.
Bioengineering (Basel) ; 10(10)2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37892865

ABSTRACT

This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 µA and 500 to 4000 µs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm2 vs. 1.06 ± 0.09 mC/cm2, p < 0.05) at a 500 µs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm2, mouse; 1.04 ± 0.09 mC/cm2, and rat; 1.16 ± 0.16 mC/cm2, p < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics.

5.
J Neural Eng ; 20(1)2023 01 20.
Article in English | MEDLINE | ID: mdl-36603218

ABSTRACT

Objective:The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU).Approach:Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2-3 mg ml-1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed.Main results:Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved.Significance:Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.


Subject(s)
Retinal Degeneration , Animals , Macaca fascicularis , Methylnitrosourea/adverse effects , Evoked Potentials, Visual , Retina/pathology , Primates , Tomography, Optical Coherence/methods
6.
Front Endocrinol (Lausanne) ; 14: 1322326, 2023.
Article in English | MEDLINE | ID: mdl-38260144

ABSTRACT

Background: Obesity is known to increase the risk and severity of age-related macular degeneration (AMD). Increased inflamed metabolic activity of visceral adipose tissue (VAT) is considered as a crucial underlying mechanism for the harmful effects of obesity. In this study, we aimed to investigate the inflamed metabolic activity of VAT with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and their association with AMD. Materials and methods: A total of 57 elderly participants (aged ≥ 50 years) who underwent 18F-FDG PET/CT for health screening and subsequent fundoscopic exam for complaint of recently impaired vision were enrolled. The metabolic activity of VAT was measured from the maximum standardized uptake value (SUVmax) of VAT. The early AMD participant was defined as the participant with either eye satisfying AMD and without any sign of advanced AMD (neovascular AMD or geographic atrophy). The late AMD participant was defined as the participant with either eye satisfying advanced AMD. Results: VAT SUVmax was highest in participants with late AMD, intermediate in early AMD, and lowest in non-AMD participants. The levels of systemic inflammation surrogate markers were also highest in late AMD group. Furthermore, VAT SUVmax was positively correlated with systemic inflammation surrogate markers and independently associated with the late AMD. Conclusions: The metabolic activity of VAT evaluated by 18F-FDG PET/CT was associated with the severity of AMD and synchronized with the level of systemic inflammation. Thus, VAT SUVmax could be potentially employed as a surrogate marker of obesity-driven VAT inflammation associated with AMD.


Subject(s)
Fluorodeoxyglucose F18 , Wet Macular Degeneration , Aged , Humans , Positron Emission Tomography Computed Tomography , Angiogenesis Inhibitors , Intra-Abdominal Fat/diagnostic imaging , Vascular Endothelial Growth Factor A , Visual Acuity , Inflammation , Obesity/complications , Obesity/diagnostic imaging , Biomarkers
7.
Front Neurosci ; 16: 1010445, 2022.
Article in English | MEDLINE | ID: mdl-36248640

ABSTRACT

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-µm-high 3D electrodes on a 200-µm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-µm-thick sloped PDMS substrate without electrodes (group 2); and a 140-µm-thick sloped PDMS substrate with 20-µm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain-optical coherence tomography (SD-OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-µm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD-OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-µm-high electrodes showed better structural compatibility than the 75-µm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-µm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

8.
J Craniofac Surg ; 33(4): e427-e429, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-36041098

ABSTRACT

ABSTRACT: The purpose of this study was to investigate the distribution of blowout fracture sites among age groups and compare clinical factors that can affect the fracture site. The authors reviewed 330 cases of blowout fracture surgeries and included 226 eyes of 226 patients aged between 20 and 29 years and between 50 and 59 years who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea University Hospital.Medical records including patient demography, trauma etiology, and preoperative computed tomography image were evaluated. Ethmoidal cell septa and fracture site position were compared between the 2 age groups. The causes of injury were categorized into 3 groups: focal trauma, gross trauma, and other causes. Orbital floor fracture was the most common type (40.00%) in the young group, followed by medial wall fracture (25.33%). in contrast, medial wall fracture accounted for the largest proportion (42.11%) in the older group, and orbital floor fracture accounted for only 26.67%. The major cause of blowout fracture in young patients was focal trauma, whereas gross trauma was the most common cause in the older group. The number of ethmoidal cells was 4.19 ±â€Š0.831 (2-6) in the young group and 3.91 ±â€Š1.022 (2-6) in the old group (P  < 0.05). Distribution of blowout fracture site differed between age groups, and these differences can be explained by cause of injury and number of ethmoidal cells.


Subject(s)
Fractures, Multiple , Orbital Fractures , Adult , Aged , Asian People , Eye , Facial Bones , Humans , Orbital Fractures/diagnostic imaging , Orbital Fractures/epidemiology , Orbital Fractures/etiology , Retrospective Studies , Tomography, X-Ray Computed , Young Adult
9.
J Craniofac Surg ; 33(4): 1190-1192, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-36041113

ABSTRACT

ABSTRACT: The purpose of this study was to investigate the characteristics of blowout fractures caused by baseball trauma. The authors reviewed 337 cases of blowout fracture surgeries and included 330 eyes of 330 patients who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea university Hospital.Medical records including patient demography, trauma etiology, accompanied ocular disease, and preoperative computed tomography images were evaluated. Patients were categorized into 2 groups: a group with blowout fracture caused by baseball trauma and another group with trauma due to other causes. Two-wall blowout fracture (orbital floor fracture and medial wall fracture) was most common (63.16%) in the baseball group, followed by medial wall fracture (21.05%). In contrast, orbital floor fracture accounted for the largest proportion (42.11%) among other causes, and 2-wall blowout fracture accounted for the second largest proportion (31.83%). The most common accompanied ocular disease was traumatic hyphema and traumatic iridocyclitis (36.84%) in the baseball blowout fracture group. in contrast, subconjunctival hemorrhage was the most common ocular disease in the other-causes group (16.08%). The frequency of traumatic hyphema and irido-cyclitis was significantly different among the 2 groups (P  < 0.05). Distribution of blowout fracture sites and frequent ocular disease differed between baseball blowout fracture patients and other-cause blowout fracture patients.


Subject(s)
Baseball , Eye Injuries , Orbital Fractures , Facial Bones , Humans , Hyphema , Orbital Fractures/diagnostic imaging , Orbital Fractures/epidemiology , Orbital Fractures/etiology , Retrospective Studies
10.
J Clin Med ; 11(12)2022 Jun 09.
Article in English | MEDLINE | ID: mdl-35743388

ABSTRACT

A single-center retrospective observational case series was conducted. This case series enrolled patients who showed ophthalmic manifestations within one week after COVID-19 vaccination at Korea University Guro Hospital in Seoul, Korea, from May 2021 to January 2022. The medical records of patients who complained of ocular symptoms and showed ophthalmic adverse events within one week after COVID-19 vaccination were reviewed. Seventeen eyes from 16 patients with a mean age of 63.8 (range 33-83) years were included in the case series, and all symptoms developed within 1-7 days following inoculation. Retinal vein occlusion in nine eyes (52.9%), retinal artery occlusion in one eye (5.9%), newly developed anterior uveitis in one eye (5.9%), exacerbation of previously diagnosed panuveitis in two eyes (11.8%), and angle-closure attack with high intraocular pressure in four eyes (23.5%) were included. Twelve patients (75%) had been vaccinated with the AstraZeneca (AZD1222) and four (25%) with the Pfizer (BNT162b2) vaccines. Of these, 10 patients (62.5%) experienced ocular disease exacerbation after the first dose, 4 (25%) after the second dose, and 2 (12.5%) after the third dose (booster shot). Eleven patients (64.7%) underwent tests for hematological abnormalities, and three of them tested positive for anti-PF4 antibodies, but no abnormal findings were noted. A causal relationship between vaccination and the ocular manifestations could not be determined, which is a limitation of this study. However, clinicians should consider the effect of COVID-19 vaccination on ophthalmic disease. Further studies are required to elucidate the possible effects of COVID-19 vaccination on the eye.

11.
Front Cell Neurosci ; 16: 889663, 2022.
Article in English | MEDLINE | ID: mdl-35602554

ABSTRACT

Retinal prostheses have shown some clinical success in patients with retinitis pigmentosa and age-related macular degeneration. However, even after the implantation of a retinal prosthesis, the patient's visual acuity is at best less than 20/420. Reduced visual acuity may be explained by a decrease in the signal-to-noise ratio due to the spontaneous hyperactivity of retinal ganglion cells (RGCs) found in degenerate retinas. Unfortunately, abnormal retinal rewiring, commonly observed in degenerate retinas, has rarely been considered for the development of retinal prostheses. The purpose of this study was to investigate the aberrant retinal network response to electrical stimulation in terms of the spatial distribution of the electrically evoked RGC population. An 8 × 8 multielectrode array was used to measure the spiking activity of the RGC population. RGC spikes were recorded in wild-type [C57BL/6J; P56 (postnatal day 56)], rd1 (P56), rd10 (P14 and P56) mice, and macaque [wild-type and drug-induced retinal degeneration (RD) model] retinas. First, we performed a spike correlation analysis between RGCs to determine RGC connectivity. No correlation was observed between RGCs in the control group, including wild-type mice, rd10 P14 mice, and wild-type macaque retinas. In contrast, for the RD group, including rd1, rd10 P56, and RD macaque retinas, RGCs, up to approximately 400-600 µm apart, were significantly correlated. Moreover, to investigate the RGC population response to electrical stimulation, the number of electrically evoked RGC spikes was measured as a function of the distance between the stimulation and recording electrodes. With an increase in the interelectrode distance, the number of electrically evoked RGC spikes decreased exponentially in the control group. In contrast, electrically evoked RGC spikes were observed throughout the retina in the RD group, regardless of the inter-electrode distance. Taken together, in the degenerate retina, a more strongly coupled retinal network resulted in the widespread distribution of electrically evoked RGC spikes. This finding could explain the low-resolution vision in prosthesis-implanted patients.

12.
Retina ; 42(3): 494-502, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34723899

ABSTRACT

PURPOSE: To evaluate the morphologic features of macular neovascularization (MNV) trunks at different layers using optical coherence tomography angiography. METHODS: Type 1 MNV trunks in age-related macular degeneration were retrospectively evaluated at the subretinal pigment epithelium and sub-Bruch membrane (subBM) layers. The detectability and location of the trunks were compared. MNV trunks at the subBM layer on optical coherence tomography angiography B-scans were evaluated using a flow overlay. The correlations of the MNV trunk with optical coherence tomography angiography and optical coherence tomography parameters were evaluated. RESULTS: Among the 63 included eyes, 27 showed core vessels at the subretinal pigment epithelium layer and 52 showed MNV trunks at the subBM layer, which were connected with the MNV at the subretinal pigment epithelium layer. The locations of the MNV trunks in each layer were different. MNV trunk types at the subBM layer were related to disease duration, distance from the large choroidal vessels, and MNV vessel density. The large choroidal vessel diameter was correlated with the MNV trunk diameter at the subBM layer. CONCLUSION: Macular neovascularization trunks at the subBM layer were detected more frequently than distal MNV trunks at the subretinal pigment epithelium layer. Macular neovascularization trunk features at the subBM layer may be related to disease duration and a large choroidal vessel.


Subject(s)
Choroidal Neovascularization/diagnosis , Computed Tomography Angiography , Retinal Neovascularization/diagnosis , Tomography, Optical Coherence , Wet Macular Degeneration/diagnosis , Aged , Aged, 80 and over , Bruch Membrane/pathology , Choroid/blood supply , Choroidal Neovascularization/physiopathology , Female , Humans , Male , Retinal Neovascularization/physiopathology , Retinal Pigment Epithelium/pathology , Retinal Vessels/pathology , Retrospective Studies , Wet Macular Degeneration/physiopathology
13.
Sci Rep ; 11(1): 24135, 2021 12 17.
Article in English | MEDLINE | ID: mdl-34921172

ABSTRACT

Retinal prosthesis is regarded as the treatment for vision restoration in the blind with retinal degeneration (RD) due to the loss of photoreceptors. A strategy for retinal prosthesis is to electrically activate surviving neurons. The retina's response to electrical stimulation in a larger RD model has not been studied yet. Therefore, in this study, we investigated electrically evoked retinal responses in a previously validated N-methyl-N-nitrosourea (MNU)-induced porcine RD model. Electrically evoked responses were evaluated based on the number of retinal ganglion cell (RGC) spikes via multichannel recordings. Stimulation pulses were applied to degenerative and wild-type retinas with pulse modulation. Compared to wild-type retinas, degenerative retinas showed higher threshold values of pulse amplitude and pulse duration. The rate of increase in the number of RGC spikes relative to stimulus intensity was lower in degenerative retinas than in normal retinas. In severely degenerated retinas, few RGCs showed electrically evoked spikes. Our results suggest that the degenerative porcine retina requires a higher charge than the normal porcine retina. In the early stage of RD, it is easier to induce RGC spikes through electrical stimulation using retinal prosthesis; however, when the degeneration is severe, there may be difficulty recovering patient vision.


Subject(s)
Evoked Potentials, Visual/drug effects , Methylnitrosourea/toxicity , Retinal Degeneration , Retinal Ganglion Cells/metabolism , Animals , Disease Models, Animal , Electric Stimulation , Female , Retinal Degeneration/chemically induced , Retinal Degeneration/metabolism , Retinal Degeneration/physiopathology , Swine , Swine, Miniature
14.
Transl Vis Sci Technol ; 10(13): 14, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34757392

ABSTRACT

Purpose: To present normative data of optical coherence tomography (OCT) parameters, electrophysiological tests, and optical biometry conducted for cynomolgus monkeys. Methods: Multimodal examinations were performed for 11 adult cynomolgus monkeys (Macaca fascicularis, weighing 2.6-7.5 kg, aged 45-99 months). A-scan biometry was performed to measure ocular biometry. OCT images were obtained at 30° and 55°. After the pupils were fully dilated, electroretinogram (ERG) and visual evoked potentials (VEP) were recorded with a commercial system using a contact lens electrode. Results: All cynomolgus monkeys were males. The mean axial length was 17.92 ± 0.34 mm. The central total retinal layer (TRL) and subfoveal choroidal thicknesses were 286.27 ± 18.43 and 234.73 ± 53.93 µm, respectively. The TRL and nerve fiber layer thickness was greater in the nasal than in other quadrants in the Early Treatment Diabetic Retinopathy Study circle in the macula. Peripheral TRL and ganglion cell complex thickness on the temporal outside the vascular arcades were lower than on the other sides. The peak latency of a-wave and b-wave in scotopic and photopic 3.0 ERG was 14.78 ± 1.00 and 32.89 ± 1.81 ms, and 12.91 ± 1.03 and 31.79 ± 2.16 ms, respectively. The n2 wave peak latency of VEP was 15.21 ± 8.07 ms. The a-wave peak latency of ERG and the n2 wave peak latency of VEP negatively correlated with age. Conclusions: The normative ocular biometric, electrophysiological test, and OCT parametric data of cynomolgus monkeys could serve as reference values for further preclinical studies. Translational Relevance: We present normative data of cynomolgus monkeys' eyes, an adequate animal model for preclinical studies.


Subject(s)
Evoked Potentials, Visual , Tomography, Optical Coherence , Animals , Biometry , Electrophysiology , Macaca fascicularis , Male
15.
Transl Vis Sci Technol ; 10(12): 3, 2021 10 04.
Article in English | MEDLINE | ID: mdl-34605876

ABSTRACT

Purpose: The purpose of this study was to present normative data of optical coherence tomography (OCT), electrophysiological, and ocular biometry parameters and their correlation in minipigs. Methods: Eighty-eight eyes of 44 minipigs underwent full-field electroretinogram (ERG) recording and ocular biometry. However, 10 eyes of 6 minipigs were excluded because of poor OCT image quality. The thickness of the retinal sublayers was measured on a vertical line at 5 locations with a 1 mm interval from the disc margin to the dorsal periphery and at 10 locations on the visual streak. Visual evoked potentials (VEPs) were measured in 15 eyes of 8 minipigs. Results: All minipigs were female with a mean age and axial length of 13.83 ± 10.56 months and 20.33 ± 0.88 mm, respectively. The implicit time of the a-wave and b-wave in scotopic 3.0 ERGs was longer than that in photopic 3.0 ERG. The implicit time of the n2-wave and p2-wave in VEP was 25.67 ± 7.41 ms and 52.96 ± 10.38 ms, respectively. The total retinal layer (TRL) and nerve fiber layer (NFL) became thinner near the periphery. The inner retinal sublayers near the visual streak were thicker than those at other locations. Central TRL and NFL thickness on visual streak was 223.06 ± 23.19 µm and 74.03 ± 13.93 µm, respectively. The temporal TRL and NFL on the visual streak were thicker than those on the nasal side. Conclusions: The normative electrophysiological and OCT parameters used in our study can be used as reference data in further pig studies. Translational Relevance: This study presents normative data of minipigs, which are adequate animal models for preclinical studies.


Subject(s)
Electroretinography , Evoked Potentials, Visual , Animals , Female , Humans , Nerve Fibers , Retina/diagnostic imaging , Swine , Swine, Miniature
16.
Sci Rep ; 11(1): 258, 2021 01 08.
Article in English | MEDLINE | ID: mdl-33420119

ABSTRACT

We aimed to develop an outer retinal degeneration pig model induced by temporary intravitreal loading of N-methyl-N-nitrosourea (MNU) during vitrectomy. In a preliminary experiment involving 5 mini-pig cases to determine the appropriate concentration of MNU, the vitreous cavity of each eye was filled with 4, 8, 10, 12, or 16 mg/mL MNU for 10 min, which was then replaced with a balanced salt solution. Multimodal examinations including spectral-domain optical coherence tomography (OCT) images and full-field electroretinography (ffERG) were obtained at baseline and week 2, week 6, and week 12. The retinal degeneration was classified according to the amplitudes of a dark adaptive (DA) 10.0 a-wave amplitude. The degree of moderate retinal degeneration was defined as DA 10.0 a-wave amplitude ≥ 10% and < 60% of baseline amplitude. The degree of severe degeneration was defined as DA 10.0 a-wave amplitude < 10% of baseline amplitude, noise, or flat signal. Hematoxylin and eosin staining and immunohistochemistry were performed at week 12. The main experiments were conducted first with 10 cases of 5 mg/mL and later with 13 cases of 10 mg/mL. In the preliminary experiment, degree of outer retinal degeneration increased with MNU concentration. Use of 4, 8, 10, 12, and 16 mg/mL MNU showed no, moderate, severe, severe, and atrophic changes, respectively. In the main experiments, there were 9 cases of moderate retinal degeneration and 1 case of severe degeneration in 5 mg/mL MNU group. Two cases of moderate degeneration and 11 of severe degeneration were recorded in 10 mg/mL group. Mean thickness of total retina, inner nuclear layer, and outer nuclear layer decreased at week 2 in both groups. The mean amplitudes on ffERG decreased at week 2. The ffERG and OCT findings did not change from week 2 to week 6 or week 12. The results of staining supported those of ffERG and OCT. Temporal MNU loading in a vitrectomized pig-eye model induced customized outer retinal degeneration with changing the concentration of MNU.


Subject(s)
Disease Models, Animal , Methylnitrosourea/toxicity , Retinal Degeneration/chemically induced , Vitrectomy/methods , Animals , Dose-Response Relationship, Drug , Electroretinography , Intravitreal Injections , Retinal Degeneration/diagnostic imaging , Retinal Degeneration/pathology , Swine , Swine, Miniature , Tomography, Optical Coherence
17.
Sci Rep ; 10(1): 18507, 2020 10 28.
Article in English | MEDLINE | ID: mdl-33116246

ABSTRACT

We sought to describe the surgical techniques required in the ab-interno method to implant subretinal prostheses in mini-pigs and suggest tips to facilitate optimal outcomes. During vitrectomy, the use of valved trocar cannulas was essential to stabilize the detached retina and implanted chip. As a first step in retinal detachment, a 23-gauge cannula with very small amount of viscoelastic material was used to establish the retinal hole and promote retinal detachment. Then, balanced salt solution was applied to increase the retinal detachment and diathermy was used to make opening for subretinal prosthesis. For easy positioning of the subretinal prosthesis, a curved laser probe was adopted when handling the subretinal prosthesis under the retina. After surgery, the sclerotomy sites were tightly sutured to prevent silicone oil leakage. Without special equipment, such as a 41-gauge tip, retinal detachment could be induced easily, while the prosthesis was also successfully inserted and manipulated under the retina without an iatrogenic retinal tear. Two weeks after the operation, the oil fully occupied the intraocular volume without leakage. The subretinal prosthesis remained stable without complication. Understanding the principle of the ab-interno method and considering several tips for improving surgical access may help to enhance surgical success rates of subretinal prostheses implantation.


Subject(s)
Prosthesis Implantation/methods , Visual Prosthesis/adverse effects , Vitrectomy/methods , Animals , Prostheses and Implants , Retina/surgery , Retinal Detachment/surgery , Retinal Perforations/surgery , Swine , Swine, Miniature , Visual Acuity
18.
Sci Rep ; 10(1): 14011, 2020 08 19.
Article in English | MEDLINE | ID: mdl-32814784

ABSTRACT

We aimed to investigate the clinical implication of suspended scattering particles in motion (SSPiM) using optical coherence tomography angiography (OCTA) among branch retinal vein occlusion disease (BRVO) cases with macular edema (ME). Medical records of BRVO patients were reviewed. Central retinal thickness (CRT), ME type, and cyst size on optical coherence tomography images were evaluated before and after intravitreal bevacizumab injection. Nonperfusion area, SSPiM, and microvascular abnormalities in OCTA images were evaluated using a Heidelberg machine. SSPiM was identified in 24 of 56 cases. There were no differences in baseline characteristics between groups with and without SSPiM. Disease duration, disease-free duration, previous injection number, microaneurysms in the superficial vascular complex, and microaneurysms in the deep vascular complex (DVC) (p = 0.003, 0.013, 0.028, 0.003, < 0.001, respectively) differed significantly between the two groups. After multivariate logistic analysis, microaneurysms in the DVC were the only different factor between the two groups (odds ratio [OR]: 0.091; p = 0.001). Furthermore, SSPiM in the DVC (OR 10.908; p = 0.002) and nonperfusion grade (OR 0.039; p < 0.001) were significantly associated with cyst response after intravitreal injection. SSPiM may be correlated with microaneurysms in the DVC and a poor anatomical response after intravitreal injection.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Bevacizumab/administration & dosage , Fluorescein Angiography/methods , Macular Edema/pathology , Retinal Vein Occlusion/pathology , Tomography, Optical Coherence/methods , Female , Humans , Intravitreal Injections , Macular Edema/drug therapy , Male , Middle Aged , Retinal Vein Occlusion/drug therapy
19.
Sci Rep ; 9(1): 14153, 2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31578437

ABSTRACT

We aimed to evaluate the relationship between the capillary abnormalities including nonperfusion area (NPA) in optical coherence tomography angiography (OCTA) images and the recurrence of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF; bevacizumab). The records of 40 patients who underwent intravitreal bevacizumab injection for ME secondary to BRVO and had at least six months of follow-up were reviewed. Central retinal thickness (CRT; µm) and macular edema type were evaluated prior to treatment. After ME resolution, nonperfusion areas in the 1 mm (NPA1) and 1-3 mm (NPA3) zones on the Early Treatment Diabetic Retinopathy Study (ETDRS) circle within the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured using OCTA images. Furthermore, other microvascular abnormalities in the both SCP and DCP were compared between groups. ME recurred in 25 of 40 (62.5%) eyes. The NPA1 of the SCP and DCP (p = 0.002, 0.004, respectively), NPA3 of the SCP and DCP (p = 0.002, 0.008, respectively), and initial CRT (p = 0.022) differed significantly between eyes with and without ME recurrence. In multivariate logistic regression analyses, the NPA1 of the DCP (OR: 344.718; p = 0.029) and NPA3 of the SCP (OR: 4.072; p = 0.018) were significantly associated with ME recurrence. Other microvascular abnormalities were not significantly different between two groups. The central NPA and parafoveal NPA of the SCP in OCTA images correlated strongly with ME recurrence in BRVO patients after intravitreal anti-VEGF injection.


Subject(s)
Angiogenesis Inhibitors/adverse effects , Bevacizumab/adverse effects , Macular Edema/diagnostic imaging , Retinal Vein Occlusion/complications , Aged , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Angiography , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Female , Humans , Intravitreal Injections , Macular Edema/etiology , Male , Middle Aged , Recurrence , Retinal Vein Occlusion/drug therapy , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Tomography, Optical Coherence
20.
Curr Eye Res ; 42(5): 666-671, 2017 05.
Article in English | MEDLINE | ID: mdl-27791390

ABSTRACT

PURPOSE: To evaluate the immediate effect of 3% diquafosol ophthalmic solution on tear MUC5AC concentration, periodic acid-Schiff (PAS)-positive goblet cells, and tear film stability in normal and keratoconjunctivitis sicca (KCS) rat models. METHODS: Rats were divided into normal and KCS groups. 3% of diquafosol solution was instilled into the right eye and normal saline into the left eye in both groups. To determine the peak time of tear MUC5AC concentration, tears were collected after 3% diquafosol instillation every 5 min up to 20 min. The tear film stability and the numbers of PAS-positive goblet cells were compared in both models. RESULTS: After diquafosol instillation, tear MUC5AC concentration increased steadily for 15 min, at which point the MUC5AC concentration reached its peak. In both normal and KCS groups, the MUC5AC concentration at 15 min was higher after instillation of 3% diquafosol solution (17.77 ± 2.09 ng/ml in the normal group, 9.65 ± 3.51 ng/ml in the KCS group) than that after saline instillation (13.74 ± 2.87 ng/ml in the normal group, 8.19 ± 3.99 ng/ml in the KCS group) (p = 0.018 for both). The corneal wetting ability was significantly longer after instillation of 3% diquafosol solution compared with that after instillation of normal saline in the normal group (p = 0.018). The percentage of PAS-positive goblet cells after the instillation of 3% diquafosol solution was significantly lower than that after instillation of normal saline in both models (p = 0.018 for both). CONCLUSIONS: Diquafosol ophthalmic solution was effective in stimulating mucin secretion in both normal and KCS rat models, and the peak time of tear MUC5AC concentration was 15 min after diquafosol instillation. The increased tear MUC5AC concentration was accompanied by improved tear film stability and a decreased percentage of PAS-positive goblet cells.


Subject(s)
Cornea/metabolism , Keratoconjunctivitis Sicca/drug therapy , Mucin 5AC/metabolism , Polyphosphates/administration & dosage , Tears/metabolism , Uracil Nucleotides/administration & dosage , Administration, Topical , Animals , Conjunctiva/drug effects , Conjunctiva/metabolism , Conjunctiva/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Goblet Cells/drug effects , Goblet Cells/metabolism , Goblet Cells/pathology , Instillation, Drug , Keratoconjunctivitis Sicca/metabolism , Keratoconjunctivitis Sicca/pathology , Male , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/pharmacokinetics , Polyphosphates/pharmacokinetics , Rats , Rats, Inbred Lew , Time Factors , Uracil Nucleotides/pharmacokinetics
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