Tomoyoshi Fujita

Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1-R) Blocker via Modulating AT1-R Signaling and Decreased Extracellular Glutamate Levels

PURPOSE To investigate the mechanism of the neuroprotective effects of the angiotensin II type 1 receptor (AT1-R) blocker against retinal ischemia-reperfusion injury in the rat. METHODS Retinal ischemia was induced by increasing intraocular pressure. Glutamate release from the rat retina and intravitreal PO(2) (partial pressure of oxygen) profiles were monitored during and after ischemia using a microdialysis biosensor and oxygen-sensitive microelectrodes. ELISA was used to measure changes in the expression of AT1-R. Retinal mRNA expressions of p47phox and p67phox were measured by real-time polymerase chain reaction. Reactive oxygen species (ROS) were measured using dihydroethidium. RESULTS Administration of candesartan, which is an AT1-R blocker (ARB), suppressed ischemia-induced increases in the extracellular glutamate. Candesartan also attenuated the increase in intravitreal PO(2) during reperfusion. AT1-R expression peaked at 12 hours after reperfusion. Although there was an increase in the retinal mRNA expression of p47phox and p64phox at 12 hours after the reperfusion, administration of candesartan suppressed these expressions. The production of ROS that was detected at 12 hours after reperfusion was also suppressed by the administration of candesartan or apocynin. CONCLUSIONS NADPH oxidase-mediated ROS production increased at 12 hours after reperfusion. Candesartan may protect neurons by decreasing extracellular glutamate immediately after reperfusion and by attenuating oxidative stress via a modulation of the AT1-R signaling that occurs during ischemic insult.

Modified vitreous surgery for symptomatic lamellar macular hole with epiretinal membrane containing macular pigment.

Modified Vitreous Surgery for Symptomatic Lamellar Macular Hole With Epiretinal Membrane Containing Macular Pigment Lamellar macular hole (LMH) was first described by Gass in 1975 as an abortive process of fullthickness macular hole formation that resulted from cystoid macular edema. In contrast, macular pseudoholes (MPHs) were attributable to centripetal contraction of the epiretinal membrane (ERM). Because spectraldomain optical coherence tomography (SD-OCT) is able to show detailed configurations of various macular conditions, this examination can be used to differentiate LMH from MPH. However, Michalewski et al used SD-OCT to demonstrate that MPH may progress to LMH, and because it is an advanced stage of the same non–full-thickness macular disorder, progression of ERM may be the cause of both MPH and LMH. Chen et al hypothesized that both entities may be different manifestations of the same disease. The ERM has been shown to coexist in most of cases with LMH. When ERM coexists with macular edema associated with branch retinal vein occlusion or diabetic retinopathy, or when it occurs after cataract surgery, LMH is secondary. In contrast, when no causative retinal diseases are present, LMH should be referred to as idiopathic. Currently, vitrectomy for LMH remains controversial. Although the natural prognosis for idiopathic LMH is usually good, some patients exhibit a visual acuity decrease that may be amenable to surgical treatment. Because LMH is usually accompanied by typical ERM, surgical treatment regularly includes ERM removal and internal limiting membrane (ILM) peeling with or without gas tamponade. In our surgical experience, LMH is frequently accompanied by ERMcontaining macular pigment, and the ERM appearing to originate from inside the LMH. Because the degree of this migration is on a case-by-case basis, a dehiscence of inner from outer retina is accompanied by a translucent ERM (posterior hyaloid membrane) alone, but not an ERM with macular pigment, in some cases with LMH. Based on the previous findings, we have speculated that ERM may contain not only macular pigment but also some partial retinal tissues. In addition, in 1989, Margherio et al described the concept of preretinal membrane dissection toward the fovea in symptomatic eyes considered to be at high risk for idiopathic macular holes development. Thus, the aim of the current study was to examine a modified surgical method for LMH with ERM containing macular pigment and then to report on the morphologic and functional outcomes of this new surgical procedure.

ASSOCIATION BETWEEN PARAFOVEAL CAPILLARY NONPERFUSION AND MACULAR FUNCTION IN EYES WITH BRANCH RETINAL VEIN OCCLUSION.

Purpose: To investigate the parafoveal perfusion status of the superficial and deep capillary layer in eyes with resolved branch retinal vein occlusion, and to study its effects on retinal sensitivity. Methods: In 27 enrolled eyes (27 patients) with resolved branch retinal vein occlusion, superficial and deep capillaries in the macular area (3- × 3-mm, centered on the fovea) were examined with optical coherence tomography angiography. Retinal sensitivity was examined with fundus-monitored microperimetry. Results: Optical coherence tomography angiography clearly showed the parafoveal superficial and deep capillaries individually. On the affected side of retina, 25 eyes (92.6%) showed capillary nonperfusion; 23 (85.2%) in the superficial layer and 22 (81.5%) in the deep layer. Capillary nonperfusions of both layers frequently overlapped and appeared to be connected with each other. Mean (±SD) retinal sensitivity at the superficial capillary nonperfusion was 19.2 ± 6.3 dB, significantly lower than that at the superficial capillary perfusion (24.4 ± 2.8 dB, P < 0.001). Similarly, mean retinal sensitivity at the deep capillary nonperfusion was 20.8 ± 5.0 dB, significantly lower than that at deep capillary perfusion (24.3 ± 2.8 dB, P = 0.0016). Mean retinal sensitivity with superficial capillary nonperfusion was significantly lower than that with deep capillary nonperfusion (P = 0.0226). Conclusion: Optical coherence tomography angiography visualized parafoveal capillary nonperfusion in superficial and deep layers individually in eyes with resolved branch retinal vein occlusion. Retinal sensitivity was significantly reduced at these capillary nonperfusions.

Metamorphopsia Associated with Branch Retinal Vein Occlusion

Purpose To apply M-CHARTS for quantitative measurements of metamorphopsia in eyes with acute branch retinal vein occlusion (BRVO) and to elucidate the pathomorphology that causes metamorphopsia. Methods This prospective study consisted of 42 consecutive patients (42 eyes) with acute BRVO. Both at baseline and one month after treatment with ranibizumab, metamorphopsia was measured with M-CHARTS, and the retinal morphological changes were examined with optical coherence tomography. Results At baseline, metamorphopsia was detected in the vertical and/or horizontal directions in 29 (69.0%) eyes; the mean vertical and horizontal scores were 0.59 ± 0.57 and 0.52 ± 0.67, respectively. The maximum inner retinal thickness showed no association with the M-CHARTS score, but the M-CHARTS score was correlated with the total foveal thickness (r = 0.43, p = 0.004), the height of serous retinal detachment (r = 0.31, p = 0.047), and the maximum outer retinal thickness (r = 0.36, p = 0.020). One month after treatment, both the inner and outer retinal thickness substantially decreased. However, metamorphopsia persisted in 26 (89.7%) of 29 eyes. The posttreatment M-CHARTS score was not correlated with any posttreatment morphological parameters. However, the posttreatment M-CHARTS score was weakly correlated with the baseline total foveal thickness (r = 0.35. p = 0.024) and closely correlated with the baseline M-CHARTS score (r = 0.78, p < 0.001). Conclusions Metamorphopsia associated with acute BRVO was quantified using M-CHARTS. Initial microstructural changes in the outer retina from acute BRVO may primarily account for the metamorphopsia.

Reduction in Dose of Intravitreous Bevacizumab Before Vitrectomy for Proliferative Diabetic Retinopathy

B evacizumab (Avastin) is a full-length recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). It has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer. Intravitreous (IV) injection of bevacizumab, 1.25 mg/0.05 mL, has been studied in patients with age-related macular degeneration, macular edema associated with retinal vein occlusion, and diabetic macular edema. Recently, bevacizumab administered prior to vitrectomy for proliferative diabetic retinopathy (PDR) was reported to reduce intraoperative bleeding. Sawada et al showed that IV bevacizumab blocked all free VEGF in the aqueous humor. However, IV bevacizumab may cause systemic adverse effects such as thromboembolic diseases or increases in systolic blood pressure. Moreover, the rapid progression of traction retinal detachment after IV injection of bevacizumab was reported. Therefore, we need to consider an appropriate dose of bevacizumab to be injected intravitreally. The purpose of this study is to elucidate whether a reduced dose (0.25 mg) of IV bevacizumab has an effect equally strong as the widely administered dose (1.25 mg) when IV bevacizumab is used as a surgical adjunct to treat PDR.

The effect of vitreomacular and cataract surgery on oxygen saturation in retinal vessels

Purpose To evaluate the effects of vitreomacular and cataract surgery on retinal oximetry in vitreomacular disease. Patients and methods Thirty-eight eyes with epiretinal membrane (ERM) and 15 with idiopathic macular hole (MH) underwent 25 gauge pars plana vitrectomy combined with cataract surgery and intraocular lens implantation. Retinal oximetry was performed using the Oxymap T1 before, 1 month, and 6 months after surgery. Oxymap T1 simultaneously captures monochrome images of the fundus at two different wavelengths of light. Built-in Oxymap Analyzer software measures the oxygen saturation and vessel diameter. Results Mean arterial oxygen saturation significantly increased from 96.8%±6.2% to 100.2%±5.8% at 1 month and to 99.6%±5.8% at 6 months after surgery (P<0.01). Mean venous oxygen saturation also significantly increased from 54.6%±7.5% to 61.2%±6.4% at 1 month and to 62.6%±5.9% at 6 months after surgery (P<0.01). Mean arteriovenous (A-V) difference decreased from 42.2%±6.6% to 39.0%±7.8% at 1 month and to 37.0%±6.9% at 6 months after surgery (P<0.01). The ERM and MH groups showed similar changes in retinal oxygen saturation. However, there were no significant changes in the caliber of major retinal vessels after surgery (from 125.2±15.2 μm to 124.0±15.4 μm in artery, from 168.7±14.6 μm to 169.8±14.6 μm in vein). Conclusion Oxymap T1 was able to measure the increase in oxygen saturation in retinal arteries and veins, which led to a decrease in the A-V difference in oxygen saturation after vitrectomy combined with cataract surgery.

Pars plana vitrectomy combined with internal limiting membrane peeling for recurrent macular edema due to branch retinal vein occlusion after antivascular endothelial growth factor treatments.

Purpose To evaluate the anatomic and functional outcomes of pars plana vitrectomy combined with internal limiting membrane peeling for recurrent macular edema (ME) due to branch retinal vein occlusion (BRVO) after intravitreal injections of antivascular endothelial growth factor (anti-VEGF) agents. Methods Twenty-four eyes of 24 patients with treatment-naive ME from BRVO were treated with intravitreal injections of anti-VEGF agents. Recurred ME was treated with pars plana vitrectomy combined with internal limiting membrane peeling. Results After the surgery, ME was significantly reduced at 1 month (P=0.031) and the reduction increased with time (P=0.007 at the final visit). With the reduction in ME, treated eyes showed a slow improvement in visual acuity (VA). At the final visit, improvement in VA was statistically significant compared with baseline (P=0.048). The initial presence of cystoid spaces, serous retinal detachment, or subretinal hemorrhage under the fovea, as well as retinal perfusion status, showed no association with VA improvement. However, the presence of epiretinal membrane showed a significant association with the visual recovery. Although eyes without epiretinal membrane showed visual improvement (−0.10±0.32 in logarithm of the minimum angle of resolution [logMAR]), eyes with epiretinal membrane showed greater visual improvement (−0.38±0.12 in logMAR, P=0.012). Conclusion For recurrent ME due to BRVO after anti-VEGF treatment, particularly when accompanied by epiretinal membrane, pars plana vitrectomy combined with internal limiting membrane peeling might be a possible treatment option.

Metamorphopsia associated with central retinal vein occlusion

This prospective study aimed to investigate metamorphopsia in eyes with central retinal vein occlusion (CRVO) and included 28 eyes (28 patients) with unilateral CRVO that had macular edema (ME) in the acute phase. The ME was treated with anti-vascular endothelial growth factor agents. At baseline and at 1 and 6 months after initiation of treatment, quantitative measurements of metamorphopsia were performed using M-CHARTS and the retinal morphologic changes were examined by optical coherence tomography. At baseline, metamorphopsia was detected on M-CHARTS in 14 (50.0%) eyes. The mean M-CHARTS score was 0.37 ± 0.53. At 1 month and 6 months after initiation of treatment, there was substantial resolution of ME and significant recovery of visual acuity. In contrast, metamorphopsia was still detected in 16 eyes at 6 months; the mean M-CHARTS scores were 0.29 ± 0.37 at 1 month and 0.32 ± 0.38 at 6 months, and had not significantly improved from baseline (p = 0.580, and p = 0.604, respectively). Although the M-CHARTS score at 6 months was associated with the baseline M-CHARTS score (p = 0.004), it did not have any associations with morphologic parameters at baseline. However, the M-CHARTS score at 6 months was significantly associated with foveal photoreceptor status, height of serous detachment, and parafoveal thickening at 1 month. Metamorphopsia associated with CRVO could be quantified using M-CHARTS, and often persisted in contrast with the recovery of visual acuity and resolution of ME after treatment with anti-vascular endothelial growth factor agents.

Combined 25-gauge vitrectomy and cataract surgery with toric intraocular lens with idiopathic epiretinal membrane

Purpose To evaluate the stability of axis rotation, astigmatism correction, and improvement in uncorrected distance visual acuity (UDVA) up to 6 months postoperatively using an astigmatism‐correcting intraocular lens (IOL) in a 25‐gauge transconjunctival sutureless vitrectomy combined with cataract surgery. Setting Department of Ophthalmology, Kagawa University Faculty of Medicine, Kagawa, Japan. Design Prospective nonrandomized interventional study. Method Eyes with a preoperative corneal cylinder of more than 0.75 diopter (D) had a triple procedure for idiopathic epiretinal membrane (ERM) using an Acrysof IQ toric IOL. Outcome measures were the amount of IOL axis rotation up to 3 months postoperatively, UDVA, corrected distance visual acuity, and corneal and refractive astigmatism up to 6 months postoperatively. A comparison was performed between patients with a target postoperative spherical refraction of emmetropia (toric emmetropic group) and patients who previously had a triple procedure for idiopathic ERM using a nontoric IOL (control group). Results The mean IOL axis rotation from the end of surgery until 3 months postoperatively was 3.67 degrees ± 3.13 (SD). Six months postoperatively, the mean corneal and refractive cylinders were 1.32 ± 0.61 D and 0.51 ± 0.31 D, respectively, showing a significant difference (P<.0001, paired t test). In addition, the mean UDVA was significantly improved 6 months postoperatively in the control and toric emmetropic group (0.57 logMAR versus 0.35 logMAR) (P=.028), although the toric group was more improved than the control group. Conclusion In vitrectomy (triple procedure) for idiopathic ERM with a toric IOL, postoperative IOL axis stability was similar to that reported for cataract surgery alone. Furthermore, the UDVA was better than with implantation of a spherical IOL. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Pars Plana Vitrectomy Combined with Internal Limiting Membrane Peeling to Treat Persistent Macular Edema after Anti-Vascular Endothelial Growth Factor Treatment in Cases of Ischemic Central Retinal Vein Occlusion

Objective: To evaluate the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling in cases of ischemic central retinal vein occlusion (CRVO) where macular edema (ME) persisted after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: Fifteen eyes with ischemic CRVO-related ME were included in the study. Nine were treated with panretinal photocoagulation after initial examination. Anti-VEGF agents were injected intravitreally. Persistent ME was treated with PPV combined with ILM peeling. During surgery, laser photocoagulation was further applied to the non-perfused area. Results: Mean retinal thickness gradually decreased after surgery (p = 0.024 at 6 months), although visual acuity did not improve significantly during the follow-up period (14.7 ± 11.6 months). Neovascular glaucoma subsequently developed in three cases and a trabeculectomy was performed in one case. Conclusion: In eyes with ischemic CRVO, PPV combined with ILM peeling contributed to a reduction in persistent ME. However, there was no significant improvement in visual acuity.