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Shumpei Obata, Yusuke Ichiyama, Masashi Kakinoki, Osamu Sawada, Yoshitsugu Saishin, Masahito Ohji Department of Ophthalmology, Shiga University of Medical Science, Shiga, JapanCorrespondence: Shumpei ObataShiga University of Medical Science, 520 – 2192, Seta Tsukinowacho, Otsu City, Shiga, JapanTel +81-77-548-2276Fax +81-77-548-2279Email obata326@belle.shiga-med.ac.jpPurpose: The classification of lamellar macular holes (LMHs) into two subtypes has recently been proposed. However, the effectiveness of vitrectomy for treatment of each type of LMH is not well established. The goal of this study was to compare functional and anatomic changes after vitrectomy between eyes with degenerative LMH and those with tractional LMH.Patients and methods: This was a retrospective analysis of the medical records of patients with LMH who underwent vitrectomy. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured preoperatively (baseline), as well as at 1, 3 and 12 months postoperatively. BCVA and CMT were compared between eyes with degenerative LMH and those with tractional LMH.Results: Thirty-two eyes met the inclusion criteria. Thirteen eyes were diagnosed with degenerative LMH and 19 eyes were diagnosed with tractional LMH. Compared with baseline BCVA, postoperative BCVA improved significantly at 12 months postoperatively: from 0.33 to 0.12 logarithm of the minimum angle of resolution (logMAR) in eyes with degenerative LMH and from 0.30 to 0.12 logMAR in eyes with tractional LMH (p < 0.05 for both comparisons). BCVA at 12 months postoperatively did not significantly differ between the two groups. CMT decreased significantly from 419.4 μm at baseline to 364.2 μm at 12 months postoperatively in eyes with tractional LMH (p < 0.05); conversely, there was no significant difference in eyes with degenerative LMH (315.5 μm baseline to 314.9 μm at 12 months postoperatively; p > 0.05).Conclusion: Vitrectomy improved BCVA in eyes with degenerative LMH as well as in eyes with tractional LMH. BCVA at 12 months postoperatively did not differ between the two groups.Keywords: lamellar macular hole, surgery, visual acuity, ellipsoid zone

Shumpei Obata,1 Tomoaki Higashiyama,1 Taku Imamura,1 Masashi Kakinoki,1 Takahide Yanagi,2 Yoshihiro Maruo,2 Masahito Ohji1 1Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan; 2Department of Pediatrics, Shiga University of Medical Science, Otsu, JapanCorrespondence: Shumpei ObataDepartment of Ophthalmology, Shiga University of Medical Science, Seta Tsukinowacho, Otsu, Shiga 520-2192, JapanTel +81-77-548-2276Fax +81-77-548-2279Email obata326@belle.shiga-med.ac.jpPurpose: To evaluate short-term changes in intraocular pressure after intravitreal injection of bevacizumab for retinopathy of prematurity.Patients and methods: This study was a prospective case-series. Consecutive infants underwent intravitreal injection with bevacizumab for type 1 retinopathy of prematurity at a university hospital. Intraocular pressure was measured with tonometer at baseline, at 1 min, and at 3, 10, 30 and 60 mins after injection.Results: Five patients (four boys) were enrolled in this study. Mean (± standard deviation) intraocular pressure was 8.0 ± 2.4 mmHg (range: 6–11.5 mmHg) just before the intravitreal injection, and the pressures were 19.8 ± 2.8 mmHg (16.4–23.9 mmHg), 14.6 ± 4.4 mmHg (7.6–18.4 mmHg), 11.2 ± 4.2 mmHg (6.4–16.5 mmHg), 9.3 ± 3.5 mmHg (5.8–13.2 mmHg), and 8.2 ± 1.4 mmHg (6.9–10.0 mmHg) at 1 min, 3, 10, 30 and 60 mins after the injection, respectively. Mean intraocular pressure after 1 min was significantly higher than intraocular pressure before injection (p = 0.02). Pressures decreased between 1 min and 3 mins after intravitreal injection, although there was no statistically significant difference between the pressures at those time-points. Intraocular pressures after 3, 10, 30 and 60 mins were not significantly different from the pressure before injection.Conclusion: Intraocular pressure elevation after intravitreal injection of bevacizumab for neonatal infants may be mild, so there may be a limited risk due to intraocular pressure after intraocular injection of bevacizumab for retinopathy of prematurity.Keywords: retinopathy of prematurity, intraocular pressure, bevacizumab

Tomoaki Higashiyama, Masahito Ohji Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan Purpose: This study was performed to observe changes prospectively in exophthalmos and orbital fat in patients with inactive thyroid-associated ophthalmopathy (TAO) treated with bimatoprost. Methods: In this 12-month single-treatment pilot observational study, 13 patients with inactive-phase TAO were administered bimatoprost to treat exophthalmos due to TAO. Exophthalmos values and orbital tissue volumes were measured on MRI by technicians in a masked fashion. Results: Nine orbits of nine patients (eight women, one man) were treated with bimatoprost for 12 months. Mean exophthalmos values before and after treatment were 21.7±2.2 and 21.7±2.0 mm, respectively. The mean value after 12 months of treatment was not significantly different from before treatment (P=0.82). Mean orbital fat volume before and after 12 months of treatment was 17.2±2.5 and 17.0±3.0 cm3, respectively. The corresponding total extraocular muscle volume was 4.0±0.7 and 3.8±0.9 cm3, respectively. Mean volume in each tissue type after 12 months of treatment was not significantly different from before treatment (orbital fat, P=0.70; extraocular muscles, P=0.32). Conclusion: Topical bimatoprost treatment did not reduce exophthalmos or orbital fat in this cohort of patients with inactive TAO. Keywords: bimatoprost, thyroid-associated ophthalmopathy, exophthalmos, orbital fat

Kanji Takahashi,1 Masahito Ohji,2 Hiroko Terasaki,3 Shigeru Honda,4 Philippe Margaron,5 Tadhg Guerin,6 Mitsuko Yuzawa,7 On behalf of the EVEREST II Japanese investigators 1Department of Ophthalmology, Kansai Medical University, Osaka, Japan; 2Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan; 3Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan; 4Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan; 5Department of Ophthalmology, Novartis Pharma AG, Basel, Switzerland; 6Department of Ophthalmology, Novartis Ireland Limited, Dublin, Ireland; 7Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan Purpose: To compare the efficacy and safety of ranibizumab 0.5 mg with or without verteporfin photodynamic therapy in Japanese patients with polypoidal choroidal vasculopathy over 12 months. Study design: EVEREST II was a 24-month, Phase IV, multicenter, randomized, double-masked study in Asian patients with symptomatic macular polypoidal choroidal vasculopathy. Methods: Of the 322 enrolled patients, 84 patients, including 46 patients who received ranibizumab + verteporfin photodynamic therapy (combination therapy arm) and 38 patients who received ranibizumab/sham PDT (monotherapy arm), were Japanese who were evaluated in this subanalysis. Mean change in best-corrected visual acuity (BCVA) and complete polyp regression at Month 12, ranibizumab treatment exposure, and safety over 12 months were assessed. Results: Baseline demographics were well balanced between the arms. At Month 12, mean change in BCVA letter score was +8.5 with combination therapy versus +6.4 with monotherapy. Complete polyp regression was higher with combination therapy than with monotherapy at Month 12 (70.5% vs 27.3%). Over 12 months, patients in the combination arm received a median of 4.0 ranibizumab injections vs 7.0 in the monotherapy arm. Serious adverse events were generally low in both arms, and retinal hemorrhage, an adverse event, was reported in one patient (2.2%). Conclusion: The results from the Japanese cohort were in agreement with the EVEREST II study. Combination therapy was effective in improving BCVA and achieving a higher rate of complete polyp regression with a lower number of ranibizumab injections than monotherapy. No new safety signals were reported, and safety events were comparable between both arms over 12 months. Keywords: Japanese, polypoidal choroidal vasculopathy, ranibizumab, neovascular age-related macular degeneration, verteporfin photodynamic therapy

Tomoaki Higashiyama,1 Yasuhiro Nishida,2 Masahito Ohji1 1Department of Ophthalmology, 2Clinical Medical Education Center, Shiga University of Medical Science, Shiga, Japan Purpose: To characterize the relationship between inflammation and swelling of extraocular muscles in thyroid-associated ophthalmopathy before and after methylprednisolone pulse therapy.Methods: 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.Result: 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 (cm3) 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

Yuka Ito, Yoshitsugu Saishin, Osamu Sawada, Masashi Kakinoki, Taichiro Miyake, Tomoko Sawada, Hajime Kawamura, Masahito Ohji Department of Ophthalmology, Shiga University of Medical Science, Otsu, Shiga, Japan Purpose: Our aim was to compare the 1 year efficacy and safety results of intravitreal bevacizumab (IVB) in two prospective, consecutive groups of patients with macular edema (ME) following branch retinal vein occlusion (BRVO).Patients and methods: Twenty-five eyes with ME after BRVO received one IVB injection (single-injection group) and 27 eyes received three monthly IVB injections (three-injection group). Both groups were followed monthly for 12 months. The best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. Patients were eligible to receive an IVB injection if the mean CFT increased 100 µm or more or the BCVA decreased 0.1 logarithm of the minimum angle of resolution (logMAR) unit or more compared with values measured on the last visit.Results: The mean logMAR BCVA and CFT, respectively, improved from 0.56 to 0.33 and from 598 µm to 348 µm in the single-injection group (P

Masato Fujikawa, Osamu Sawada, Taichiro Miyake, Masashi Kakinoki, Tomoko Sawada, Hajime Kawamura, Masahito Ohji Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan Purpose: To determine the role of vascular endothelial growth factor (VEGF) in macular edema secondary to branch retinal vein occlusion (BRVO). Patients and methods: Aqueous humor samples were collected from 52 eyes with macular edema secondary to BRVO before intravitreal drug injections and from 62 control eyes with cataract. VEGF was measured using an enzyme-linked immunosorbent assay. Fluorescein angiography showed capillary nonperfused areas (NPAs). Macular edema was evaluated by optical coherence tomography as the central retinal thickness. Results: The mean aqueous VEGF levels in eyes with BRVO and control eyes with cataract were, respectively, 290.5 pg/mL ± 294.9 pg/mL (range 81.9 pg/mL-1567.3 pg/mL) and 118.0 pg/mL ± 50.1 pg/mL (range 24.6 pg/mL-241.1 pg/mL), which differed significantly (P < 0.0001). The mean VEGF level in eyes with BRVO without apparent NPA was 171.4 pg/mL ± 52.5 pg/mL (range 90.9 pg/mL-299.9 pg/mL), which was significantly higher than controls (P = 0.001). VEGF levels were correlated positively with the size of NPA (P = 0.0002) but not with the central retinal thickness. Conclusion: The aqueous VEGF concentration in patients with macular edema secondary to BRVO increased significantly and was correlated significantly with the size of NPA. Aqueous VEGF increased even in eyes without apparent NPA. Keywords: aqueous humor, branch retinal vein occlusion, macular edema

Hirokazu Sakaguchi,1 Masahito Ohji,2 Yusuke Oshima,1 Yasushi Ikuno,1 Fumi Gomi,1 Naoyuki Maeda,1 Motohiro Kamei,1 Shunji Kusaka,3 Kohji Nishida11Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, 2Department of Ophthalmology, Shiga University of Medical Science, Otsu, 3Department of Ophthalmology, Sakai Hospital Kinki University Faculty of Medicine, Sakai, JapanBackground: To assess time-course changes in best-corrected visual acuity (BCVA) up to 5 years after vitrectomy to treat idiopathic full-thickness macular holes (MHs) and identify the relationship of the changes to postoperative complications.Methods: Twenty-three consecutive patients with an idiopathic MH underwent vitrectomy without adjuvant treatment. BCVA and complications were assessed postoperatively.Results: Twenty-two of 23 (95.7%) MHs closed after the first surgery, with a final anatomic success rate of 100%. The time course of the BCVA was analyzed in 20 cases in which data were obtained for over 5 years. The BCVA improved by 0.43 logarithm of the minimum angle of resolution (logMAR) unit 6 months postoperatively (P < 0.001) and continuously improved by 0.05, 0.06, and 0.07 logMAR units between 6 months and 1 year, 1 year and 3 years (by 0.11 logMAR unit between 6 months and 3 years; P = 0.049), and 3 years and 5 years (P = 0.018) postoperatively, respectively. Macular complications developed in seven (35%) of the 20 cases; the mean BCVA at 5 years in these cases was significantly (P < 0.001) worse than in cases without complications.Conclusion: The BCVA might improve gradually for 5 years after vitrectomy to treat MHs. However, the macular complications that can develop postoperatively could limit that possibility.Keywords: macula hole, time course, vitrectomy, retina, visual acuity, complication