Development of chemical vitrectomy with plasminogen

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2003～2005課題番号: 15591855研究代表者: 大路 正人（滋賀医科大学・医学部・教授

Comparison of Macular Thickness in Diabetic Macular Edema Using Spectral-Domain Optical Coherence Tomography and Time-Domain Optical Coherence Tomography

Purpose. To compare the macular thicknesses in diabetic macular edema (DME) measured with spectral-domain optical coherence tomography (SD-OCT) and time-domain (TD) OCT. Patients and Methods. The average macular thicknesses of 50 eyes of 29 patients with DME were measured using SD-OCT and TD-OCT. Results. The mean macular thicknesses measured with TD-OCT and SD-OCT were 401.5 ± 117.8 μm (mean ± SD) and 446.2 ± 123.5 μm, respectively. The macular thicknesses measured with the two devices were well correlated (Pearson's product moment correlation, r = 0.977, P < 0.001). A significant correlation was found between the best-corrected visual acuity and the retinal thickness measured by TD-OCT and SD-OCT (Pearson's product moment correlation, TD-OCT, r = 0.34; P < 0.05; SD-OCT, r = 0.32; P < 0.05). Discussion. The mean macular thickness measured with SD-OCT was about 45 μm thicker than that measured with TD-OCT. Attention should be paid when comparing data obtained using different OCT machines

Vogt-Koyanagi-Harada Disease-Like Uveitis during Nivolumab (Anti-PD-1 Antibody) Treatment for Metastatic Cutaneous Malignant Melanoma

Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody that is used to treat metastatic cutaneous malignant melanoma. Although bilateral uveitis has been reported as a side effect of nivolumab administration, there are few reports of Vogt-Koyanagi-Harada disease (VKH)-like uveitis. We report such a case. A 63-year-old woman with metastatic cutaneous malignant melanoma experienced visual loss in both eyes 10 days after her second nivolumab injection. Her decimal best-corrected visual acuity (BCVA) was 0.7 in the right eye and 0.4 in the left eye. Examination revealed bilateral granulomatous keratic precipitates and posterior synechiae in the left eye. Optical coherence tomography showed multiple sites of serous retinal detachment (SRD) in the left eye and wavy retinal pigment epithelium in both eyes. Fluorescein angiography revealed multiple pinpoint-sized areas of leakage in both eyes and active leakage from the disc in her right eye. Indocyanine green angiography (IA) showed choroidal hyperfluorescence due to choroidal vascular leakage, with hypofluorescent dark spots during the late phase. These findings supported a diagnosis of VKH-like uveitis following nivolumab injections. Nivolumab was discontinued because of headache. Anterior chamber inflammation disappeared 3 weeks after starting topical corticosteroid treatment, and the SRD disappeared within 3 months. Her decimal BCVA recovered to 1.0 in the right eye and to 0.9 in the left eye. Also, the fluorescein angiography and IA findings had improved by 4 months. We concluded that careful follow-up is required after nivolumab treatment because VKH-like panuveitis might develop

Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States

BACKGROUND AND OBJECTIVE: To evaluate comparability of abicipar pegol (abicipar) effects in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in Japan and the United States. PATIENTS AND METHODS: Phase 2, multicenter, randomized, double-masked, 20-week studies (BAMBOO, Japan; CYPRESS, United States). Patients (n = 25 each study) received three monthly intravitreal injections of abicipar 1 mg or 2 mg or five monthly intravitreal injections of ranibizumab 0.5 mg. RESULTS: Mean best-corrected visual acuity change from baseline at week 16 (primary endpoint) for abicipar 1 mg, abicipar 2 mg, and ranibizumab was +7.8 letters, +8.9 letters, and +17.4 letters (BAMBOO); +4.4 letters, +10.1 letters, and +15.2 letters (CYPRESS). Mean central retinal thickness change from baseline was −187.3 μm, −196.5 μm, and −230.4 μm (BAMBOO); −106.5 μm, −112.8 μm, and −124.4 μm (CYPRESS). Uveitis or vitritis was reported in three abicipar-treated patients. CONCLUSION: Abicipar demonstrated extended duration of effect and safety that were comparable between Japanese and non-Japanese patients with nAMD. Abicipar effectively treated Japanese patients with polypoidal choroidal vasculopathy

Changes in the anterior segment after cycloplegia with a biometer using swept-source optical coherence tomography.

The aim of this study was to investigate changes in the anterior segment of the eye after cycloplegia. A biometer combined with swept-source optical coherence tomography (SSOCT) was used for measurements. Patients with strabismus or amblyopia who underwent cycloplegia were included. The axial length, central corneal thickness, anterior chamber depth, and lens thickness were measured with the biometer-SSOCT system before and after cycloplegia. Altogether, 10 eyes of 10 patients (mean age 7.20 ± 3.08 years, range 4-14 years) were evaluated. The mean measurements before cycloplegia were 22.75 ± 0.96 mm axial length, 516 ± 33 μm central corneal thickness, 3.40 ± 0.21 mm anterior chamber depth, and 3.77 ± 0.26 mm lens thickness. The corresponding values after cycloplegia were 22.75 ± 0.95 mm, 519 ± 34 μm, 3.68 ± 0.16 mm, and 3.42 ± 0.20 mm, respectively. The mean lens thickness had significantly decreased (P < 0.001) after cycloplegia, and the mean anterior chamber depth had significantly increased (P < 0.001). The means of the axial length (P = 0.66) and central corneal thickness (P = 0.17) had not changed significantly. The change in lens thickness was significantly correlated with the change in anterior chamber depth (r = -0.73, P = 0.02). The new biometer-SSOCT combination proved useful for accurately detecting changes in the anterior segment of the eye after cycloplegia in pediatric patients. The biometer\u27s measurements indicated increased anterior chamber depth and decreased lens thickness after cycloplegia. The anterior chamber depth increased relative to the decrease in lens thickness

Optical coherence tomography angiography in eyes with good visual acuity recovery after treatment for optic neuritis.

To evaluate the retinal perfusion using optical coherence tomography (OCT) angiography in eyes with good visual acuity recovery after treatment for optic neuritis (ON).Seven eyes of seven patients with good visual acuity recovery after treatment for monocular ON and seven eyes of each fellow eye used as controls were studied. Retinal perfusion around the disc and at the macula was evaluated using OCT angiography. The retinal nerve fiber layer thickness was measured around the disc. The ganglion cell layer complex thickness or the ganglion cell layer plus the inner plexiform layer thickness were measured at the macula.The retinal perfusions in all eyes with ON decreased around the disc and at the macula compared with those of the fellow eyes, as shown by OCT angiography (disc, P = 0.003; macula, P = 0.001). The retinal thicknesses in all eyes with ON also decreased around the disc and at the macula compared with those of the fellow eyes (disc, P < 0.001; macula, P = 0.003).Optic neuritis may cause not only retinal structural damage but also decreased retinal perfusion, even after the visual acuity recovered well after treatment

Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study.

Purpose:To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study.Methods:Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study.Results:The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF.Conclusion:IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not.Trial registration: ClinicalTrials.gov Identifier: NCT02305238. (http://clinicaltrials.gov/show/NCT02305238

Quantitative Analysis of Inflammation in Orbital Fat of Thyroid-associated Ophthalmopathy Using MRI Signal Intensity.

We quantitatively analyzed inflammation in orbital fat from cases of thyroid-associated ophthalmopathy (TAO) using short-tau inversion recovery (STIR) sequences from magnetic resonance imaging. The signal intensity ratios (SIRs) of orbital fat as well as the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles on STIR images were measured in 70 eyes from 70 treatment-naive TAO patients (active TAO group, 19 patients; inactive TAO group, 51 patients) and 20 eyes from 20 controls. The mean SIR in the active TAO group was significantly higher than that in the inactive TAO group and controls (P < 0.001). The SIR of orbital fat in all TAO patients was significantly (P < 0.001) positively correlated with that of the extraocular muscles: SR (r = 0.64), IR (r = 0.55), LR (r = 0.58), MR (r = 0.71), and SO (r = 0.65). The SIR of orbital fat had a significant positive correlation with the CAS (r = 0.53, P < 0.001). The measurements of SIRs in orbital fat may be useful in evaluating the activity in tissues of TAO patients

Relationship between magnetic resonance imaging signal intensity and volume of extraocular muscles in thyroid-associated ophthalmopathy with methylprednisolone pulse therapy.

To characterize the relationship between inflammation and swelling of extraocular muscles in thyroid-associated ophthalmopathy before and after methylprednisolone pulse therapy.The signal intensities and volumes of the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles were measured with magnetic resonance imaging in 25 eyes of 25 patients with thyroid-associated ophthalmopathy in the acute inflammatory phase before and after methylprednisolone pulse therapy. The signal intensity ratios (SIRs) of muscles and brain white matter were calculated.The mean SIRs before treatment were 2.28±0.74 in SR, 2.66±0.57 in IR, 2.03±0.42 in LR, 2.45±0.49 in MR, and 1.98±0.48 in SO muscles. The mean SIRs after treatment were 1.82±0.62, 1.84±0.52, 1.70±0.35, 1.95±0.46, and 1.60±0.36, respectively. The mean volumes (cm(3)) before treatment were 1.35±0.67 in SR, 1.21±0.39 in IR, 0.66±0.13 in LR, 0.94±0.31 in MR, and 0.58±0.14 in SO muscles. Those after treatment were 1.12±0.45, 0.91±0.31, 0.61±0.12, 0.85±0.28, and 0.49±0.11, respectively. The SIRs showed significantly positive correlations with volumes both before and after treatment in SR muscles (before, r=0.77; after, r=0.69), IR muscles (before, r=0.65; after, r=0.60), MR muscles (before, r=0.69; after, r=0.73), and SO muscles (before, r=0.52; after, r=0.50) (P<0.01 for all correlations).Swelling reflected the inflammation in extraocular muscles of thyroid-associated ophthalmopathy both before and after treatment

Usefulness of Intravitreal Bevacizumab for Retinopathy of Prematurity with Severely Dilated Tunica Vasculosa Lentis and Poor Mydriasis.

Laser therapy has been the gold standard treatment for retinopathy of prematurity (ROP), while intravitreal bevacizumab (IVB) is reported to be of significant benefit for zone I ROP. A problem with laser therapy is that it is difficult to administer in ROP patients with severely dilated tunica vasculosa lentis and poor mydriasis. However, although IVB treatment has been performed in such severe ROP cases, only 1 report has discussed its usefulness. Case1:A male infant was born with a birth weight of 382 g at 23 weeks\u27 gestation. As visualization was poor and laser therapy could not be performed due to dilated tunica vasculosa lentis and poor mydriasis, IVB (0.625 mg/0.025 mL) was administered to both eyes. Following treatment, the ROP gradually improved, with regression of the dilated tunica vasculosa lentis and improvement of the mydriasis in both eyes. Case2:A male infant was born with a birth weight of 698 g at 25 weeks\u27 gestation. As laser therapy could not be performed due to severely dilated tunica vasculosa lentis and poor mydriasis, IVB (0.625 mg/0.025 mL) was administered to both eyes. Following treatment, the ROP gradually improved, with regression of the dilated tunica vasculosa lentis and improvement of the mydriasis in both eyes. Conclusion:IVB is potentially more useful than laser therapy for the treatment of severe ROP with dilated tunica vasculosa lentis and poor mydriasis