Effect of the macular shape on hole findings in idiopathic macular hole differs depending on the stage of the macular hole.

This study aimed to investigate the relationship between macular shape and idiopathic macular hole (MH) findings using an objective method. We present retrospective observational case series on patients with MH. The shape of the macular area was quantified using quadratic equations, and the ocular shape (OS) index was calculated. The correlation between the OS index and macular hole findings for each stage was evaluated. Pearson's correlation coefficient showed a significant correlation between the OS index and horizontal hole diameter (p = 0.044), bottom diameter (p = 0.006), and vertical bottom diameter (p = 0.024) in stage 2. For stage 4, there was a negative and significant correlation between the OS index and age (p = 0.037), and horizontal (p = 0.021) and vertical (p = 0.027) bottom diameter. Multiple regression analysis showed that the horizontal (p = 0.0070) and vertical (p = 0.031) bottom diameter and OS index were independently and positively correlated in stage 2. In stage 4, the OS index was independently and negatively correlated with the horizontal (p = 0.037) and vertical (p = 0.048) bottom diameter. The ocular shape of the macula affects MH findings, and its impact depends on its stage.

Increased incidence of endophthalmitis after vitrectomy relative to face mask wearing during COVID-19 pandemic.

BACKGROUND/AIMS: To determine the incidence and causative pathogens of endophthalmitis after vitrectomy during strict face mask wearing in the COVID-19 period. METHODS: This was a retrospective multicentre study including 31 ophthalmological institutions of the Japanese Retina and Vitreous Society or Japan-Clinical Retina Study group. Patients who had undergone vitrectomy during 2019, the pre-COVID-19 period, and from July 2020 to June 2021, the COVID-mask period, were studied. The results of cataract surgery were used as a control. The total number of vitrectomies and the total number of postoperative endophthalmitis were determined. Then, the differences in the incidence of postoperative endophthalmitis between the pre-COVID-19 period and the COVID-mask period, and the type of pathogens causing the endophthalmitis were studied. RESULTS: The incidence of postvitrectomy endophthalmitis was significantly lower in the pre-COVID-19 period with 16 568 surgeries and 18 endophthalmitis cases (0.11%) than in the COVID-mask period of 14 929 surgeries and 31 endophthalmitis cases (0.21%; p=0.031, OR=1.913, 95% CI 1.078 to 3.394). In the pre-COVID-19 period, 4 of the 18 eyes were culture positive, and all were of the Staphylococcus family. In the COVID-mask period, 9 of the 31 eyes were culture positive, and 4 cases were related to oral commensals including Streptococcus spp, which are reportedly very rare in endophthalmitis after vitrectomy. CONCLUSIONS: It is necessary for physicians to be aware of the higher incidence of postvitrectomy endophthalmitis during the COVID-mask period, and to treat their patients appropriately.

OCULAR FACTORS RELATED TO PREOPERATIVE ENLARGEMENT OF IDIOPATHIC MACULAR HOLE DIAMETER.

PURPOSE: To determine the preoperative factors that are significantly correlated with an enlargement of an idiopathic macular hole (MH) during the one-month preoperative period. METHODS: This was a retrospective cross-sectional study of patients with MH who had undergone vitrectomy in the Kagoshima University Hospital. The stage of the MH was determined by using spectral domain optical coherence tomography. Patients who had optical coherence tomography images at two time points more than 14 days apart before the vitrectomy were studied. RESULTS: The MH participants were at Stage 2 in 44 eyes, at Stage 3 in 58 eyes, and at Stage 4 in 38 eyes. The rate of increase of the hole diameter was 26.0 ± 42.3% at Stage 2, 5.52 ± 15.5% at Stage 3, and 8.04 ± 18.7% at Stage 4. The rate of change at Stage 2 was significantly greater than that at Stage 3 and Stage 4 (both P < 0.01). In Stage 2, the MH diameter at the initial visit was significantly and negatively correlated with the rate of MH enlargement (r = -0.35, P = 0.021). CONCLUSION: Patients with Stage 2 MHs, especially eyes with small hole diameter, should be considered for early surgery.

Silicone oil versus gas tamponade for primary rhegmatogenous retinal detachment treated successfully with a propensity score analysis: Japan Retinal Detachment Registry.

BACKGROUND/AIMS: To compare the effects of silicone oil tamponade (SOT) to that of gas tamponade (GT) on the best-corrected visual acuity (BCVA) after successful vitrectomy for retinal detachment (RD). METHODS: A retrospective, multicentre, nationwide study with RD who were registered in the Japan-RD Registry. All cases with RD treated with successful vitrectomy between February 2016 and March 2017 were studied. A propensity score matching was performed using the preoperative findings as covariates to adjust the relevant confounders. The primary outcome was the estimated mean difference of the postoperative BCVA in 6 months between eyes treated with SOT to those treated with GT. RESULTS: Of the 3446 cases registered, 2097 cases met the entry criteria. There were 2042 eyes that had GT and 55 eyes that had SOT. Primary success was defined as a reattached retina with no tamponade at 6 months. After propensity score matching, each group contained 40 cases. The preoperative BCVA was 0.966±0.738 logMAR units in the GT group and 1.270±0.945 logMAR units in the SOT group (p=0.177). Six months postoperatively, the BCVA in the GT group was significantly better at 0.309 logMAR units in the GT group than the 0.671 logMAR units in the SOT group (p=0.002). CONCLUSIONS: Even after successful surgery for RD, eyes that experienced SOT had poorer BCVA than eyes treated with GOT. SOT should be considered cautiously. PRECIS: Propensity score analysis of eyes with rhegmatogenous RD showed that postoperative vision was worse in eyes treated once with silicone oil than with gas even after completely successful surgery.

Comparison of multicolor scanning laser ophthalmoscopy and optical coherence tomography angiography for detection of microaneurysms in diabetic retinopathy.

This study aimed to evaluate the usefulness of multicolor (MC) scanning laser ophthalmoscopy (MC-SLO) in detecting microaneurysm (MA) in eyes with diabetic retinopathy (DR). This was a retrospective cross-sectional study. Eyes with DR underwent fluorescein angiography (FA), MC-SLO, optical coherence tomography angiography (OCTA), and color fundus photography (CFP) were analyzed. The foveal region was cut in an 6 × 6 mm image and the number of MA in each image was counted by retina specialists to determine the sensitivity and positive predictive value. FA results were used as the ground standard. MAs were classified as those with early, late, or no dye leakage based on FA images. Fifty-four eyes of 35 patients with an average age of 64.5 ± 1.24 years were included. The sensitivity of MA detection was 37.3%, 15.3%, and 4.12% in MC-SLO, OCTA, and CFP, respectively (P < 0.01 in each pair).The positive predictive value was 66.4%, 46.4%, and 27.6% in MC, OCTA, and CFP, respectively (P < 0.01 in each pair). Sensitivity for MAs with early leakage was 36.4% in MC-SLO, which was significantly higher than 4.02% in OCTA. MC-SLO was more useful in detecting MA in eyes with DR than OCTA.

Best surgical technique and outcomes for large macular holes: retrospective multicentre study in Japan.

The purpose of this study was to compare the surgical outcomes of vitrectomy with conventional internal limiting membrane (C-ILM) peeling to that with the inverted ILM (I-ILM) flap technique for large macular holes (MHs). This was a retrospective chart review of consecutive cases with a large MH at nine hospitals in Japan. Among the 1342 eyes, 165 eyes of 165 cases met the inclusion criteria. The results for medium-large MHs with a diameter 400-550 µm were compared to that of eyes with an extra-large MH with a diameter >550 µm. In addition, the results of C-ILM peeling were compared to that of the I-ILM technique. In medium-large MHs, the closure rate was 95.2% (59/62) by C-ILM peeling and 100% (19/19) by the I-ILM technique. In extra-large MHs, the closure rate was 88.4% (38/43) by C-ILM peeling and 100% (41/41) by I-ILM. Although the difference between the two methods was not significant, the I-ILM technique was successful in 100% of the cases. Multiple logistic regression analysis showed the best-corrected visual acuity (BCVA) at 6 months was significantly associated with the preoperative BCVA, MH size, age and sex of the patient. Analyses of the eyes with extra-large MHs show that the surgical success is high, and the I-ILM technique is more effective for closure in eyes with extra-large MHs.

Effect of fluid-air exchange on reducing residual silicone oil after silicone oil removal.

PURPOSE: Our purpose was to determine the effect of fluid-air exchange on the amount of silicone oil (SO) droplets remaining in the vitreous cavity after removal of the main body of the SO. METHODS: This was a retrospective comparative study of 56 eyes of 56 patients that had undergone vitrectomy with SO tamponade. Fluid-air exchange was performed during surgery in 30 eyes [Air Ex(+) group] and was not done in 26 eyes [Air Ex(-) group]. All of the eyes were examined by ultrasonography, and the images were converted to binarized image. The amount of residual SO droplets/vitreal area in the images was expressed as the, "silicone oil index (SOI)". The correlations between SOI and clinical findings were determined. RESULTS: The SOI was significantly correlated with the axial length (AL, R = 0.444, P = 0.023). The SOI in the Air Ex(+) group was significantly higher (7.4 ± 2.6%) than in the Air Ex(-) group (4.9 ± 3.4%; P = 0.004). Multiple linear regression analyses showed that the SOI was independently and significantly correlated with the AL and the Air Ex(+) group (P = 0.003, P = 0.006, respectively). CONCLUSIONS: Fluid-air exchange during vitrectomy to remove residual SO is not effective. Our findings indicate that it may increase the amount of residual SO droplets.

Minification of fundus optical coherence tomographic images in gas-filled eye.

BACKGROUND: Optical coherence tomography (OCT) is being used increasingly to evaluate and manage a variety of retinal diseases, but not much is known about the minification of the OCT images in gas-filled eyes. The purpose of this study was to investigate the effect of gas-filled eyes on the size of the OCT images. METHODS: This was retrospective case series of 81 consecutive eyes of 79 patients who had macular hole surgery between April 2012 and September 2014. Images of the optic disc were taken with a spectral domain-OCT instrument 2 days after surgery in gas-filled, pseudophakic eyes and from the same eyes but fluid-filled one month after the surgery. The vertical length, horizontal width, and the area of the optic disc were measured in the OCT images. RESULTS: Clear images were obtained from 50 eyes of 49 patients (mean age 66.4 ± 5.9 years). The mean vertical length and mean horizontal width of the optic disc in the gas-filled eyes were about 25 % shorter than that of fluid-filled eyes (vertical, 1213.8 ± 170.5 and 1650.6 ± 195.9 µm, P < 0.01; horizontal, 1169.4 ± 143.1 and 1526.4 ± 219.9 µm, P < 0.01). The mean area of the optic disc was 1.12 ± 0.34 mm(2) in gas-filled eyes which was significantly smaller than that in fluid-filled eyes (1.88 ± 0.37 mm(2)) by 40.4 %. CONCLUSIONS: The fundus images of gas-filled eyes are significantly smaller than that in the same fluid-filled eyes. The minification of the OCT images should be considered when analyzing images obtained from gas-filled eyes. TRIAL REGISTRATION NUMBER: UMIN000007517 . Date of registration: 3/21/2012.

AMOUNT OF RESIDUAL SILICONE OIL IN VITREOUS CAVITY IS SIGNIFICANTLY CORRELATED WITH AXIAL LENGTH.

PURPOSE: To determine the parameters of the eye that are significantly correlated with the amount of residual silicone oil remaining after most of it is removed by vitrectomy. METHODS: Nineteen eyes of 19 patients who had silicone oil removed were studied. The day after the surgery for silicone oil removal, B-scan ultrasonography was performed, and the residual silicone oil droplets were observed as hyperechoic particles in the ultrasonographic images. The images of the vitreous cavity were binarized, and the ratio of area of hyperechoic particles to the total vitreous area was quantified and named the silicone oil index (SOI). The correlations between SOI and clinical findings were determined. RESULTS: The SOI was significantly and positively correlated with the axial length (AL) and the preoperative intraocular pressure (AL, R = 0.676, P = 0.002; preoperative intraocular pressure, R = 0.771, P < 0.001). Partial correlation analysis showed that the AL remained significantly correlated with the SOI but the preoperative intraocular pressure was not (AL, R = 0.734, P = 0.001; preoperative intraocular pressure, R = 0.417, P = 0.096). None of the other clinical factors was significantly correlated with the SOI. CONCLUSION: Considering the significant correlation between the amount of residual silicone oil and the AL of the eye, myopic eyes should be carefully scrutinized for residual silicone oil.

Wider retinal artery trajectories in eyes with macular hole than in fellow eyes of patients with unilateral idiopathic macular hole.

PURPOSE: To determine whether the width of the retinal artery (RA) trajectory was associated with the presence of a macular hole (MH). METHODS: A retrospective cross sectional case-control study was performed. The fundus photographs were rotated 90 degrees, and the coordinates of the best fit curve of the RA trajectory were determined automatically based on these plots using the ImageJ program. The converted coordinates were fit to a second degree polynomial (ax2/100 + bx + c) equation. The width and steepness of the RA trajectory, "a", of the eyes with a MH eye were compared to that of the fellow eyes. RESULTS: One hundred and ten eyes of 55 consecutive patients (30 women) with a unilateral MH and healthy fellow eyes were analyzed. The mean age was 64.9 years (range 47-81 years). The constant 'a' was significantly smaller in eyes with a MH than that of the fellow eyes (0.379 ± 0.094 vs 0.416 ± 0.121, P = 0.001, paired t test), indicating that the RA trajectory was wider in the MH eyes than in the fellow eyes. There was a significant correlation between the axial length and 'a' of the RA trajectory in the MH eyes (R = 0.273, P = 0.044) and in the fellow eyes (R = 0.356, P = 0.008; Spearman's rank correlation coefficient). CONCLUSIONS: Because eyes with a MH have a significantly wider and flatter RA trajectory, there may be greater traction on the fovea which is located between the RA arches. The causative role of this finding is still unclear.

Individualized, spectral domain-optical coherence tomography-guided facedown posturing after macular hole surgery: minimizing treatment burden and maximizing outcome.

PURPOSE: To evaluate the individualized, optical coherence tomography-guided facedown posturing after macular hole (MH) surgery in minimizing the burden and maximizing outcome. METHODS: A retrospective comparative study. One hundred and seven consecutive eyes with an MH (<500 µm) received vitrectomy and gas tamponade. After surgery, optical coherence tomography examination was performed from 6 hours to postoperative Day 2. In Group A, with a pro re nata posturing protocol, the duration of facedown posturing was determined from the optical coherence tomography findings. Group A was subdivided as follows: Group A1, facedown posturing required postoperatively and Group A2, no posturing required. When MH closure was confirmed, facedown posturing (if any) was discontinued. If the MH did not close, additional posturing was advised. Group B was the control group, consisted of 42 consecutive eyes with traditional 7 days of posturing. RESULTS: After a single surgery, Group A had the MH closure rate of 96.2%, 95.8% in Group A1 and 97.1% in Group A2, whereas Group B had the MH closure rate of 95.2%. The average posturing period was 42 hours for Group A, 57 hours for Group A1 and 10 hours for Group A2 (P < 0.001). The MH size was correlated significantly with the closure time (R = 0.47, P = 0.005, Spearman correlation coefficient). CONCLUSION: A pro re nata posturing protocol achieves a high MH closure rate with a significant reduction of posturing time especially for pseudophakic eyes.

Relationship between supernormal sectors of retinal nerve fibre layer and axial length in normal eyes.

PURPOSE: To determine the effect of the axial length on the supernormal and false-positive sectors of the peripapillary retinal nerve fibre layer (RNFL) in healthy eyes using the normative database embedded in a spectral domain optical coherence tomographic (SD-OCT) instrument. METHODS: This was a prospective, observational cross -sectional study. The right eyes of 126 healthy young volunteers were studied. The RNFL thickness was measured by SD-OCT in twelve 30-degree sectors (clock hours) around the optic disc. The sectors whose RNFL thickness was <5% probability level were labelled as false-positive sectors. The sectors >95% probability level were labelled as supernormal sectors. The relationships between the axial length and rates of supernormal and false-positive sectors were investigated. RESULTS: A longer axial length was significantly associated with an increase in the rates of supernormal thickness in sector 8 (odds ratio, [OR], 1.494; p = 0.010) and sector 10 (OR, 1.529; p = 0.008). The supernormal sectors were mainly located in the temporal region. A longer axial length was significantly associated with a higher rates of false positives in sector 5 (OR, 1.789; p = 0.017), sector 6 (OR, 2.305; p < 0.001) and sector 12 (OR, 2.277; p = 0.035). CONCLUSIONS: The axial length was significantly related to the rates of supernormal and false-positive sectors even in healthy eyes. These findings indicate that the specificity and sensitivity of SD-OCT will be affected especially in eyes with longer axial lengths.

[Application of ultrasound-enhanced gene and drug delivery to the ocular tissue].

Visual images provide an immensely rich source of information about the external world. Eye has characteristic structure sensory cells are arranged along the eye wall, and is filled inside with vitreous body. In recent years, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent had widely spread, and numerous number of patients who suffered ocular angiogenic disease such as diabetic retinopathy, age-related macular degeneration and retinal vascular occlusion for the disease, were treated and spared the blindness. Vitreous cavity was regarded as reservoir of drug, intravitreal injection is thought a sort of drug delivery. However, with regard to the administration of a selective drug deliver, it has not yet been solved. Our aim is to establish a new method of gene transfer, drug delivery using low-energy ultrasound to the eye, to date, we confirmed drug and gene deliver to the ocular tissue such as cornea, conjunctiva and retina with high efficiency. In addition, tissue damage was minimal. We have also shown that ultrasound irradiation with combination of a microbubbles or bubble liposome could be introduced drug and gene more effectively. Based on these knowledge, we will focus on development of a new device for intraocular ultrasound exposure and potential for therapeutic application of ultrasound to humans retinal disease such as retinal artery obstruction.

Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab.

BACKGROUND: To determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory. METHODS: Eyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss' kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography. RESULTS: Among the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P < .001, Mann-Whitney U test). The inter-rater agreement was high with a Fleiss' kappa = 0.95, P < .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann-Whitney U test). CONCLUSIONS: Eyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy.

Relationship between position of peak retinal nerve fiber layer thickness and retinal arteries on sectoral retinal nerve fiber layer thickness.

PURPOSE: We determined the relationship between the position of the peak of the retinal nerve fiber layer (RNFL) thickness, and the retinal arteries, axial length (AL), and sectoral RNFL thickness in healthy eyes. METHODS: A prospective, observational cross-sectional study (registration number, UMIN000006040) of 50 healthy right eyes (mean age 25.8 ± 3.7 years) was performed. The RNFL thickness was measured by optical coherence tomography in twelve 30° sectors (clock hours) around the optic disc. The RNFL nasal-superior-temporal-inferior-nasal curves and fundus photographs were used to measure the angles between the supratemporal and infratemporal peak RNFL positions (peak angle), and the retinal artery angle (artery angle), respectively. The relationships between the peak angle, artery angle, AL, and sectoral RNFL thickness were investigated by linear regression analyses. RESULTS: The peak angles were highly correlated with the artery angle (r = 0.92, P < 0.001) and correlated negatively with the AL (r = -0.49, -0.38; P < 0.01). After excluding the effect of the AL, the peak and artery angles were correlated significantly with the sectoral RNFL thickness in 8 sectors. After excluding the effect of the peak angle, the AL was correlated significantly with the sectoral RNFL thicknesses in only one sector. CONCLUSIONS: The temporal RNFL thickness increased as the superior and inferior RNFL peaks, and retinal arteries shifted toward the fovea, whereas an inverse relationship was observed for the inferior and supranasal areas. The sectoral RNFL thickness is correlated better with the peak and artery angles than the axial length. (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary &recptno=R000007154&language=J number, UMIN000006040.).

Early imaging of macular hole closure: a diagnostic technique and its quality for gas-filled eyes with spectral domain optical coherence tomography.

BACKGROUND/AIMS: This study was conducted to establish a reliable method to determine macular hole (MH) closure of gas-filled eyes. METHOD: 21 consecutive eyes with MH underwent vitrectomy with gas tamponade, and spectral domain optical coherence tomography (SD-OCT) was performed using our diagnostic technique. The quality of OCT images was rated as signal strength (SS) and evaluated by masked observers. RESULTS: The quality to determine MH closure (SS ≥4) was sufficient in all eyes. In addition, SD-OCT images (SS ≥6) obtained from 16/21 eyes showed detailed retinal structures including the inner segment/outer segment line. The next day after surgery, MH closure was confirmed in 12/21 eyes, and residual MH was observed in 9/21 eyes. Among these 9 eyes, 7 eyes were closed within 2 weeks. CONCLUSION: The present method provided clear SD-OCT images from gas-filled eyes, which is not only essential for the diagnosis of MH closure but also for establishing proper protocols and for studying the pathology of gas-filled eyes.

Comparison of foveal microstructure imaging with different spectral domain optical coherence tomography machines.

PURPOSE: To investigate the reproducibility of imaging the foveal microstructures of healthy eyes with 3 spectral domain optical coherence tomography (SD-OCT) machines: Cirrus (Carl Zeiss Meditec Inc.), Spectralis (Heidelberg Engineering), and Topcon (Topcon 3D OCT-1000 Mark II). DESIGN: Cross-sectional, prospective, noninterventional study. PARTICIPANTS: Images were obtained for 50 eyes of 50 healthy undilated volunteers without ocular pathology in a clinical setting. METHODS: The fovea of all subjects was imaged using Cirrus, Spectralis, and Topcon. MAIN OUTCOME MEASURES: Among the 4 hyperreflective bands in the outer subfovea on SD-OCT imaging, the innermost band (external limiting membrane [ELM] band), the second innermost band (second band), and the third innermost band (third band) were classified as "continuous," "disrupted," or "none" by 2 independent raters. Weighted κ-coefficient analysis and/or Fisher exact test were used to compare interrater, intermachine, and intramachine agreement measurements. The sensitivity of each machine was also evaluated. RESULTS: The group of 50 subjects consisted of 22 men and 28 women, with an average age of 31.4 years (range, 21-52 years). Interrater agreement for 3 bands was high (κ = 0.876, 0.738, and 0.774) with Cirrus, Spectralis, and Topcon, respectively. The sensitivity of each machine was high for the ELM band (0.92, 0.98, and 0.96), the second band (all 1.00), and the third band (0.96, 0.94, and 0.88) with Cirrus, Spectralis, and Topcon, respectively. The sensitivity of the third band was significantly lower than the second band with Topcon (Fisher exact test, P = 0.027), but the difference was not significant with the other machines. Intermachine agreement was fair to moderate for the third band (κ = 0.65, 0.512, and 0.464) and for all bands (κ = 0.531, 0.369, and 0.362) between Cirrus-Spectralis, Spectralis-Topcon, and Topcon-Cirrus, respectively; however, it was not significant for ELM band (κ = -0.027) between Spectralis-Topcon. CONCLUSIONS: In healthy adults with normal vision, there was almost perfect reproducibility between raters for foveal microstructural images acquired with the Cirrus, Spectralis, and Topcon devices. The machines have good sensitivity to image foveal microstructures, and the sensitivity does not differ significantly among machines; however, they are not necessarily identical or interchangeable for imaging certain structures.

Selective gene transfer to the retina using intravitreal ultrasound irradiation.

This paper aims to evaluate the efficacy of intravitreal ultrasound (US) irradiation for green fluorescent protein (GFP) plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 µL) and bubble liposomes (BLs; 50 µL) was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM) of GFP-positive cells (32 ± 4.9; n = 7; P < 0.01 ). No GFP-positive cells were observed in the control eyes (n = 7). Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value.

Repeatability and reproducibility of subfoveal choroidal thickness in normal eyes of Japanese using different SD-OCT devices.

PURPOSE: To compare subfoveal choroidal thickness (SCT) measurements of three different commercially available spectral-domain optical coherence tomography instruments with healthy eyes of Japanese. METHODS: A prospective, cross-sectional study was performed at a single institution. SCT of the right eye of 43 normal subjects was measured using three different SD-OCTs: Heidelberg Spectralis-OCT (Spectralis), Cirrus HD-OCT (Cirrus), and Topcon 3D OCT-1000 Mark II (Topcon). Two separate measurements were performed for the same eye with a maximum by a single examiner. SCT was defined as the distance from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction. After manual segmentation, measurements were made using calipers equipped on each machine by masked raters. Intraclass, interrater, and intermachine agreements were assessed. RESULTS: Forty-three subjects (mean age, 30.5 years) were enrolled. Of 43 eyes, the SCT of 39 eyes (90.7%) could be measured using each machine. Intraclass correlation coefficients (95% confidence intervals) were 0.976 (0.954-9.987), 0.958 (0.919-0.978), and 0.939 (0.895-0.971) with Spectralis, Cirrus, and Topcon, respectively. Interrater correlation coefficients (95% confident interval) were 0.944 (0.893 to 0.971), 0.956 (0.831 to 0.983), and 0.924 (0.825 to 0.964) with Spectralis, Cirrus, and Topcon, respectively. The average SCT was 272.6, 272.8, and 269.2 µm with Spectralis, Cirrus, and Topcon, respectively. The intermachine correlation coefficient was significantly high among the machines (P<0.001, Spearman), 0.97 (Spectralis-Cirrus), 0.96 (Cirrus-Topcon), and 0.98 (Topcon-Cirrus). Bland-Altman plot analysis showed no typical trend among the machines. CONCLUSIONS: SCT measurements obtained with three different SD-OCTs were highly correlated and could be used interchangeably. (http://upload.umin.ac.jp number, UMIN000005287.).

Sonothrombolysis for intraocular fibrin formation in an animal model.

Vascular diseases such as diabetic retinopathy or retinal arterial occlusion are always associated with retinal and/or choroidal vasculopathy and intravascular thrombosis is commonly found. The ultrasound (US) therapy is a recently developed technique to accelerate fibrinolysis and it is being applied to some clinical fields. The present study was to observe the effects of extraocular US exposure on intraocular fibrin, which is a deteriorating factor in various ocular diseases. Tubes containing human blood (2 mL) in the following groups were irradiated with US; US alone, US with tissue plasminogen activator (tPA), tPA alone, and saline (control). Fibrinolysis was quantified by measuring D-dimer after 2h. In rat eyes, intracameral fibrin (fibrin formation in the anterior chamber of the eye) was induced by YAG-laser-induced iris bleeding. Then, eyes in the following groups were irradiated with US; US alone, subconjunctival tPA alone, US and subconjunctival tPA, control. Intracameral fibrin was scored on day 3 (3+ maximum to 0). The temperatures of rat eyes were measured by infrared thermography. Histologic evaluation was also performed. D-dimer was increased by US with statistical significance (p <0.05) or tPA (p <0.01). D-dimer in US with tPA group was significantly higher than either US alone or tPA alone group (p <0.01). In rat eyes, the average intracameral fibrin score on day 3 was 1.4 in control group and 1.2 in subconjunctival tPA alone group; however, it decreased significantly in the US alone group (0.75; p <0.05, vs. control), US and subconjunctival tPA group (0.71; p <0.01, vs. control). The temperature was less than 34 degrees C after US exposure. No histologic damage was observed. US irradiation from outside accelerated intracameral fibrinolysis without causing apparent tissue damage. This noninvasive method might have therapeutic value for intraocular fibrin.