Decreased Presence of Mast Cells in the Bursa Premacularis of Proliferative Diabetic Retinopathy.

INTRODUCTION: We previously reported that the intravitreal activities of chymase and tryptase were more increased in the patients with macular hole (MH) and epiretinal membrane (ERM) than in those with proliferative diabetic retinopathy (PDR) and that the source of these serine proteases might be mast cells in the bursa premacularis (BPM). The purpose of this study was to compare the density of mast cells in BPM samples obtained from MH, ERM, and PDR patients. METHODS: BPM and vitreous core samples were first collected during vitrectomy from eyes afflicted with vitreoretinal diseases (MH: 6 eyes, ERM: 3 eyes, and PDR: 9 eyes), and then were stained with hematoxylin, toluidine blue, antibodies against chymase and tryptase, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay kit. RESULTS: Hematoxylin nuclear staining showed fewer positive-staining cells in the BPM samples obtained from PDR patients than in those obtained from MH and ERM patients. Toluidine blue staining of the BPM revealed metachromasia in the mast cells of the patients with MH and ERM, but not those of the patients with PDR. In addition, immunostaining using anti-chymase and anti-tryptase antibodies showed that the BPM samples were more intensely stained than the vitreous core samples from the patients with MH and ERM and that both tissue samples were poorly stained in the patients with PDR. The apoptotic cells were more frequently observed in the BPM samples from patients with MH than in those from patients with PDR. CONCLUSIONS: These findings indicated that lower activities of chymase and tryptase in the vitreous of PDR patients appeared to be attributable to the decreased presence of mast cells in the BPM. The lack of mast cells in the BPM might be related to the pathogenesis of PDR.

Expression of Lymphatic Markers in the Berger's Space and Bursa Premacularis.

We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger's space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals.

Type III uveal effusion syndrome suspected to be related to pachychoroid spectrum disease: A case report.

INTRODUCTION: We report a case of type III uveal effusion syndrome (UES) suspected to be related to pachychoroid spectrum disease. PATIENT CONCERNS: A 42-year-old man became aware of visual field constriction and deterioration of visual acuity in his right eye. DIAGNOSIS: Upon examination, a bullous non-rhegmatogenous retinal detachment was observed in the inferior 2 quadrants of the right eye fundus, and the subretinal fluid moved with postural changes. The axial length in that eye was 22.36 mm, thus indicating no nanophthalmia. Preoperative indocyanine green angiography revealed dilated choroidal vessels in the posterior pole of the right eye and mild leakage in the late phase. Optical coherence tomography examination revealed choroidal thickening in both eyes. INTERVENTIONS: For treatment, we first performed sclerotomy, and the intraoperative findings showed no thickening of the sclera. Following surgery, reattachment of the retina was not achieved. OUTCOMES: Thus, we next performed vitrectomy, which led to successful reattachment of the retina. LESSONS: In this case, we theorize that pachychoroid spectrum disease might have been involved in the pathogenesis of type III UES.

Effects of an Aquaporin 4 Inhibitor, TGN-020, on Murine Diabetic Retina.

PURPOSE: To investigate the effect of a selective aquaporin 4 (AQP4) inhibitor, 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), on the expression of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) production, as well as on the retinal edema in diabetic retina. METHODS: Intravitreal injections of bevacizumab, TGN-020, or phosphate-buffered saline (PBS) were performed on streptozotocin-induced diabetic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. Protein levels of VEGF from collected retinas were determined by Western blot analysis. In addition, retinal vascular leakage of Evans Blue was observed in the flat-mounted retina from the diabetic rats in the presence or absence of TGN-020. Volumetric changes of rat retinal Müller cells (TR-MUL5; transgenic rat Müller cells) and intracellular levels of ROS were determined using flow cytometry analysis of ethidium fluorescence in the presence or absence of TGN-020 or bevacizumab under physiological and high glucose conditions. RESULTS: In the diabetic retina, the immunoreactivity and protein levels of VEGF were suppressed by TGN-020. AQP4 immunoreactivity was higher than in the control retinas and the expressions of AQP4 were co-localized with GFAP. Similarly to VEGF, AQP4 and GFAP were also suppressed by TGN-020. In the Evans Blue assay, TGN-020 decreased leakage in the diabetic retinas. In the cultured Müller cells, the increase in cell volumes and intracellular ROS production under high glucose condition were suppressed by exposure to TGN-020 as much as by exposure to bevacizumab. CONCLUSION: TGN-020 may have an inhibitory effect on diabetic retinal edema.

Scleral patch grafting for scleral wound thinning after pars plana phacoemulsification and aspiration: A case report.

RATIONALE: Here we report the case of a patient who required closure with an autologous scleral patch graft during reoperation after developing marked scleral thinning in the late stage after pars plana phacoemulsification and aspiration (PPPEA). To the best of our knowledge, this is the first reports of the procedure being used for the treatment of a thinned scleral section post PPPEA. PATIENT CONCERNS: This study involved a 73-year-old woman who had undergone vitreous surgery combined with PPPEA for retinal detachment in her right eye 8 years earlier and subsequently underwent intraocular lens (IOL) ciliary sulcus suture fixation. DIAGNOSES: She became aware of visual disturbance in her right eye and slit-lamp examination revealed the dislocation of the IOL. INTERVENTIONS: To remove the dislocated IOL and resuture the nasal loop back onto the ciliary sulcus of the patient's right eye, a 25-guage trocar was placed on the superior temporal side. OUTCOMES: Subsequent removal of the trocar from the patient's right eye left an approximately 3-mm-wide oval-shaped gap at the trocar insertion site due to extreme thinning of the sclera in that area; that is, the location where the PPPEA was performed. Since suture fixation failed to stop intraocular fluid leakage, an inferior free half-thickness scleral flap was created to patch the scleral wound. Postsurgery, the leakage in that eye stopped and the intraocular pressure was stable. No complications were observed during the 1-year-postoperative follow-up period. LESSONS: Since thermal injuries during PPPEA may lead to postoperative scleral thinning, surgeons should avoid the site of a prior PPPEA when constructing a scleral wound during reoperation.

Involvement of premacular mast cells in the pathogenesis of macular diseases.

We previously reported on the elevated intravitreal activities of tryptase and chymase in association with idiopathic epiretinal membrane (ERM) and idiopathic macular hole (MH). In this present study, we investigated the potential intraocular production of these serine proteases, and measured and compared tryptase and chymase activities in the vitreous body and serum in ERM, MH, proliferative diabetic retinopathy (PDR), and rhegmatogenous retinal detachment (RRD) patients. In addition, nuclear staining with hematoxylin and eosin (H&E) and mast-cell staining with toluidine blue were performed on samples of the vitreous core and bursa premacularis (BPM) of MH. We also performed immunostaining on the above two regions of vitreous samples for MH with anti-tryptase antibody, anti-chymase antibody, anti-podoplanin antibody, anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) antibody, and anti-fibroblast antibody. Moreover, we performed immunostaining with anti-tryptase antibody and anti-chymase antibody on ERMs collected intraoperatively. Tryptase activity in the vitreous body was significantly higher in ERM and MH than in PDR. However, no significant differences were observed in the tryptase activity in the serum among these four diseases. Chymase activity in the vitreous body was significantly higher in MH than in the other three diseases, yet chymase activity in the serum was below detection limit in any of the diseases. Nuclear staining with H&E revealed an abundance of nuclei in the BPM region, but few in the surrounding area. Mast-cell staining with toluidine blue revealed that the BPM showed metachromatic staining. In immunostaining with anti-fibroblasts antibody, anti-tryptase antibody, anti-chymase antibody, anti-podoplanin antibody, and anti-LYVE-1 antibody, the BPM stained more strongly than the vitreous core. Tryptase and chymase-positive cells were also observed in ERM. These findings revealed that the presence of mast cells in the BPM potentially represent the source of these serine proteases. Moreover, the BPM, as a lymphatic tissue, may play an important role in the pathogenesis of macular disease.

Data on the involvement of endothelin-1 (ET-1) in the dysregulation of retinal veins.

Retinal vein occlusion (RVO) is a common vascular disease of the retina; however, the pathogenesis of RVO is still unclear. Branch RVO (BRVO) commonly occurs at the arteriovenous crossing and it was formerly believed that the diseased artery mechanically compresses the vein. However, it has been reported that the retinal vein runs deep beneath the artery at the arteriovenous crossing in eyes with an arterial overcrossing, and the venous lumen often appears to be preserved, even at the arteriovenous crossing, as shown by optical coherence tomography. Paques et al. [1] found venous nicking without arteriovenous contact using adaptive optics imaging. Thus, we investigated the potential role of a dysregulation of the retinal vein. While the pathogenesis of retinal vein occlusion (RVO) is still unclear, systemic hypertension and increased level of endothelin-1 (ET-1) are known risk factors (Flammer and Konieczka, 2015) [2]. We focused on the behavior of retinal veins in spontaneous hypertensive rats (SHR). Then, one of the retinal veins became exceptionally constricted and was nearly occluded (Fig. 1), and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the intravenous injection of ET-1. In addition, immunoreactivity to ET-A receptor was higher in SHR retinas than in control (WKY; Wistar Kyoto rat) retinas (Fig. 2). The protein levels of ET-A receptor and HIF-1 were also significantly higher in SHR retinas than in WKY retinas (Fig. 3). We observed vasoactivity of retinal veins; a retinal venous constriction (Kida et al., 2018) [3]. This supports the hypothesis that ET-1 can constrict retinal veins, thus increasing retinal venous pressure, and that ET-1 may even contribute to the pathogenesis of RVO.

Vasoactivity of retinal veins: A potential involvement of endothelin-1 (ET-1) in the pathogenesis of retinal vein occlusion (RVO).

PURPOSE: Whilst the pathogenesis of retinal vein occlusion (RVO) is still unclear, systemic hypertension and increased level of endothelin-1 (ET-1) are known risk factors. Therefore, we studied the influence of ET-1 on the retinal veins in hypertensive rats. METHODS: We focused on the behavior of retinal veins in spontaneous hypertensive rats (SHR). To determine whether ET-1 was associated with the blood flow in eyes of SHRs, the chorioretinal blood flow in the rats was assessed using laser speckle flowgraphy (LSFG-Micro, Softcare, Fukuoka, Japan) before and after an intravenous injection of ET-1 under general anesthesia. In addition, retinas from SHRs and age-matched normotensive Wistar-Kyoto rats (WKYs) were removed, and retinal sections were immunostained for the ET-A and ET-B receptors. The protein levels of both ET-1 receptors and hypoxia-inducible factor 1 (HIF-1) in the retinal tissues were also determined by western blot analysis. RESULTS: One of the retinal veins became exceptionally constricted and was nearly occluded, and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the injection of ET-1. Immunoreactivity to ET-A receptor was higher in SHR retinas than in WKY retinas. The protein levels of ET-A receptor and HIF-1 were also significantly higher in SHR retinas than in WKY retinas. CONCLUSIONS: An increase of ET-1 in circulating blood leads to the local constriction of retinal veins and this effect is accentuated in hypertensive rats by an upregulation of ET-A receptor. It is plausible that such a constriction of retinal veins increases retinal venous pressure, and may even contribute to the pathogenesis of RVO.

Bilateral rhegmatogenous retinal detachment due to unusual retinal degeneration in Down syndrome: A case report.

RATIONALE: The aim of this study was to report a case of Down syndrome (DS) complicated with bilateral retinal detachment (RD) due to unusual retinal degeneration. PATIENT CONCERNS: A 9-year-old girl complained of bilateral visual disturbance during a follow-up examination for myopia and strabismus. DIAGNOSES: Slit-lamp examination revealed moderate posterior subcapsular cataract in both eyes. B-mode echography showed bilateral bullous RD; however, it was difficult to detect the causal retinal breaks due to poor mydriasis. INTERVENTIONS: For treatment, the patient underwent bilateral lensectomy, vitrectomy, and silicone oil tamponade. OUTCOMES: Intraoperative findings revealed symmetrical retinal breaks and unusual caterpillar-like retinal degeneration on the upper temporal side of both eyes. Three months later, the patient underwent bilateral silicone oil removal and intraocular lens implantation. LESSONS: In this case, the retinal degeneration was morphologically different from retinal lattice degeneration, thus suggesting that it might be involved in the onset of DS-related bilateral RD.

Two Cases of Rhegmatogenous Retinal Detachment Associated with Asteroid Hyalosis.

BACKGROUND: To report two cases of rhegmatogenous retinal detachment (RRD) associated with asteroid hyalosis (AH). CASE PRESENTATION: Two patients presented with RRD originating from a flap tear. Case 1 involved a 62-year-old male who was found to have bullous RRD in his left eye originating from a flap tear. During vitreous surgery, a thick vitreous cortex was found to have strongly adhered to the entire retinal surface, from the center to the periphery. A bimanual method was then used in conjunction with the vitrectomy to create an artificial posterior vitreous detachment. After surgery, the retina was successfully reattached, and his corrected visual acuity (VA) improved. Case 2 involved a 70-year-old male who was found to have localized RRD in his left eye originating from a flap tear. During vitreous surgery, a thick vitreous cortex was found to have strongly adhered to the entire retinal surface. After surgery, the retina was successfully reattached, and his corrected VA improved. CONCLUSIONS: RRD associated with AH presents with stronger vitreoretinal adhesion compared to typical RRD, thus requiring a more complicated surgical technique to properly treat the patient.

Long-term evaluation of spontaneous release of epiretinal membrane and its possible pathogenesis.

PURPOSE: To investigate the characteristics in spontaneous release of epiretinal membrane (ERM) during watchful waiting and to introduce a possible mechanism of pathogenesis as a photo essay. METHODS: Records from all patients with ERM were obtained from Osaka Medical College Hospital from January 2001 to October 2012. Visual acuity (VA), fundus photo, and optical coherence tomography (OCT) were reviewed using the medical records. For statistical analysis, VA measured with a Landolt chart was converted to the logarithm of the minimum angle of resolution (logMAR). To investigate the pathogenesis of ERM, tryptase activity in vitreous, which plays a role in tissue fibrosis and remodeling, was measured in patients that underwent a vitrectomy for ERM, macular hole, and proliferative diabetic retinopathy (PDR). RESULTS: ERM was observed in 604 patients and spontaneous release of the ERM was observed in 13 patients with 14 eyes (four males and nine females, aged 33-78 years). Among the 14 eyes, mean VA did not change significantly through the release of the ERMs (0.17±0.18 before and 0.24±0.40 after release, P=0.544). Nine eyes showed posterior vitreous detachment or vitreomacular traction on OCT images and five eyes did not. ERM was released in five eyes with no accompanying vitreous traction by OCT during watchful waiting and seems to have peeled off by itself by contracting and rolling from the inferior side. Three eyes with deteriorated VA underwent vitrectomy due to macular hole or pseudomacular hole. Vitreal tryptase activity was significantly higher in patients with ERM compared to those with PDR (P<0.05). CONCLUSION: Fundus photos of ERM auto-peeling were taken during long-term follow-up. Spontaneous release of ERM is possibly involved in vitreous traction or membrane contraction. In addition, tryptase may be involved in the development and contraction of ERM.

A case of pseudoxanthoma elasticum with proliferative diabetic retinopathy.

BACKGROUND: To report the case of a patient with pseudoxanthoma elasticum (PXE) and proliferative diabetic retinopathy (PDR), and discuss the relationship between PXE and diabetic retinopathy (DR). CASE PRESENTATION: A 47-year-old man with PXE presented with angioid streaks and DR in both eyes, and bilateral panretinal photocoagulation was performed for treatment. Vitrectomy had previously been performed in his right eye for vitreous hemorrhage due to PDR. Systemic findings included multiple, discrete, symmetrical, small yellow papules bilaterally in the axilla and inguinal region. Examination on presentation showed vitreous hemorrhage in his left eye, and vitrectomy was performed for treatment. Intraoperative findings showed fibrovascular membrane around the optic disc and vascular arcade. A mottled fundus (peau d'orange appearance) associated with angioid streaks was also present, yet there was no evident choroidal neovascularization (CNV). The postoperative course was satisfactory, and corrected visual acuity improved from 0.02 to 0.7 diopters. CONCLUSION: Despite the peau d'orange appearance in both eyes of this case, no CNV was evident. The vitreous hemorrhage was thus attributed to PDR. Moreover, we reviewed the published literature and discuss the relationship between PXE and DR.

P7C3 Suppresses Neuroinflammation and Protects Retinal Ganglion Cells of Rats from Optic Nerve Crush.

Purpose: To determine whether P7C3-A20 can inhibit the phosphorylation of the mammalian target of rapamycin (mTOR), depress neuroinflammation, and protect retinal ganglion cells (RGCs) of rats from optic nerve crush (ONC). Methods: The left optic nerve was crushed, and 5.0 mg/kg/d of P7C3-A20, 1.0 mg/kg/d of rapamycin, or their vehicle was injected intraperitoneally for 3 consecutive days beginning 1 day before the ONC. The protective effects on the RGCs were determined by immunohistochemical staining for Tuj-1. The level of phosphorylated mTOR was determined by immunoblotting. The neuroinflammation in the optic nerve was determined by changes in the expression of CD68, TNF-α, MCP-1, and iNOS. Results: The density of Tuj-1-stained cells in the control was 2010 ± 81.5/mm2 and 1842 ± 80.4/mm2 on days 7 and 14 after the sham operation. These levels were lower at 995 ± 122/mm2 and 450 ± 52.4/mm2 on days 7 and 14 after the ONC, respectively. Rapamycin and P7C3-A20 preserved the density at significantly higher levels on both days (P < 0.05, Scheffe test). The level of phosphorylated mTOR increased by 1.56-fold above the control level on day 7. Rapamycin and P7C3 significantly lowered the level of phosphorylated mTOR to 0.89-fold and 0.67-fold of the control, respectively. There was an accumulation of CD68+ cells that were immunoreactive to TNF-α at the crush site. The expression of MCP-1 and iNOS was increased chiefly in the astrocytes around the lesion. These inflammatory events were suppressed by both rapamycin and P7C3. Conclusions: P7C3-A20 can inhibit mTOR phosphorylation in the crushed optic nerve, which may suppress neuroinflammation and preserve the RGCs.

The effect of vitreomacular adhesion in exudative age-related macular degeneration on the results of ranibizumab intravitreal injection.

PURPOSE: To investigate whether vitreomacular adhesion (VMA) affects the outcome of anti-vascular endothelial growth factor (VEGF) therapy for the treatment of exudative age-related macular degeneration (AMD) in Japanese patients. SUBJECTS AND METHODS: Of 88 Japanese AMD patients (28 men and 60 women, mean age: 72.7±7.5 years) who underwent intravitreal injection of ranibizumab for 3 years from 2010 to 2013, this study involved 12 eyes of 12 patients (10 men and two women) in whom VMA was observed based on optical coherence tomography (OCT) findings (VMA [+] group) and 17 eyes of 16 patients (seven men and nine women, control group) in whom no VMA was observed (VMA [-] group). In all enrolled patients, ranibizumab was administered monthly for 3 months, and then administered as needed (ie, pro re nata) when deterioration was observed. The two groups were then compared in regard to changes in visual acuity (VA) and the frequency of ranibizumab administration over a 1-year period. RESULTS: No significant difference was found between the two groups in regard to the transformation of the mean logarithm of the minimum angle of resolution VA change after the first visit. Over the 1-year treatment, the mean frequency of ranibizumab administration for the VMA (+) group was 5.6±2.5 times and for the VMA (-) group was 3.8±1.1 times, thus illustrating a significant difference between the two groups (Mann-Whitney's U-test: P<0.05). CONCLUSION: Our findings show that the mean frequency of ranibizumab administration for the VMA (+) group was higher than that in the VMA (-) group, thus indicating that VMA might possibly be involved in the progress of AMD pathology.

A comparison of sex steroid concentration levels in the vitreous and serum of patients with vitreoretinal diseases.

The purpose of this study was to compare steroid hormone concentration levels in the vitreous and serum of vitreoretinal disease patients to elucidate the possibility of neurosteroid production in the retina. Serum and vitreous samples were collected from vitrectomy patients, and estradiol (E2) and testosterone (T) concentrations were measured using electro-chemiluminescence immunoassay. We measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18), proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n = 19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17) cases. No statistically significant age differences existed among the groups. Mean respective E2 concentrations (pg/ml) in the male/female vitreous were ERM: 6.67±4.04/18.82±7.10, MH: 10.3±7.02/17.00±4.8, PDR: 4.2±3.05/15.83±3.46, and RD: 10.00±4.58/16.06±4.57, while those in serum were ERM: 31.67±5.51/5.82±1.08, MH: 21.00±8.89/7.53±3.2, PDR: 29.20±7.07/12.75±10.62, and RD: 24.33±6.51/7.5±4.42. E2 concentrations were significantly higher (P<0.001) in the male serum than vitreous, yet significantly higher in the female vitreous than serum. Mean respective T concentrations (ng/ml) in the male/female vitreous were ERM: 0.15±0.03/0.15±0.01, MH: 0.15±0.01/0.15±0.01, PDR: 0.15±0.03/0.16±0.12, and RD: 0.14±0.01/0.17±0.08, while those in serum were ERM: 4.54±1.46/0.16±0.01, MH: 8.04±2.29/0.16±0.10, PDR: 5.14±1.54/0.22±0.11, and RD: 3.24±0.75/0.17±0.10. T concentrations were high in the male serum, yet extremely low in the male and female vitreous and female serum. High concentrations of E2 were found in the vitreous, and women, in particular, exhibited significantly higher concentrations in the vitreous than in the serum. This finding suggests the possibility that in vitreoretinal disease cases, the synthesis of E2 is increased locally only in female eyes.

A Case of Diabetic Macular Edema with Prominent Chorioretinal Folds.

PURPOSE: To report a case of diabetic macular edema with prominent chorioretinal folds. CASE REPORT: This study involved a 55-year-old male with untreated bilateral diabetic retinopathy who had undergone cataract surgery at another clinic. Following that surgery, diabetic macular edema rapidly exacerbated, accentuating marked cystoid macular edema and radial chorioretinal folds in the macula. Investigation of his medical history revealed that in addition to diabetes, he had uncontrolled hypertension and severe diabetic nephropathy. Vitreous surgery was performed on both eyes due to a resistance to a subtenon injection of triamcinolone acetonide or intravitreal injection of an antivascular endothelial growth factor agent. After surgery, the macular edema and chorioretinal folds showed a tendency towards improvement. Thereafter, kidney transplant surgery was performed for renal failure, and a mild tendency of chorioretinal folds was observed. CONCLUSION: In the case presented in this study, we observed remarkable cystoid macular edema in the fovea centralis and theorize that distortion with the surrounding tissue might have occurred, thus leading to the formation of chorioretinal folds around the macula.

Case of asteroid hyalosis that developed severely reduced vision after cataract surgery.

BACKGROUND: To report our findings in a patient with asteroid hyalosis (AH) who had a severe reduction of his visual acuity following cataract surgery. The vision was improved by vitreous surgery. CASE PRESENTATION: The patient was an 81-year-old man. Following cataract surgery on his left eye, his decimal best-corrected visual acuity (BCVA) was markedly reduced from 0.2 to 0.02. A large number of asteroid bodies (ABs) was observed to be concentrated on the posterior surface of the implanted intraocular lens. Ultrasound B-mode images showed turbidity of the vitreous that was denser in the anterior vitreous where the ABs were concentrated. During vitrectomy, the ABs were observed to be concentrated in the anterior vitreous cavity, and a complete posterior vitreous detachment (PVD) was present. After vitrectomy successfully removed the ABs, the visibility of the fundus improved and the BCVA recovered to 1.0. CONCLUSION: We suggest that the visual impairment after the cataract surgery was due to the concentrated ABs in the anterior vitreous cavity. The clustering of the ABs in the anterior vitreous cavity was most likely caused by the PVD that developed during the cataract surgery.

Two Cases of Proliferative Diabetic Retinopathy with Marked Sheathing of the Retinal Arteries following Vitrectomy.

PURPOSE: The aim of this paper was to report 2 patients (3 eyes) with proliferative diabetic retinopathy (PDR) who showed marked sheathing of the retinal arterioles that was ultimately attributed to calcification following vitrectomy. CASES: Case 1 involved a 65-year-old female with PDR who underwent bilateral vitrectomy for traction retinal detachment. Postoperatively, bilateral retinal redetachment (reRD) was observed. Sheathing of the retinal arterioles was observed at the same time, yet was not apparent preoperatively. Case 2 involved a 71-year-old female with PDR who underwent vitrectomy for vitreous hemorrhage. Postoperatively, reRD was observed, and fundus findings showed sheathing of the retinal arterioles. In both patients, silicone oil tamponade and retinopexy were performed at reoperation, but sheathing of the retinal arterioles persisted postoperatively. Fluorescein fundus angiography showed that retinal blood flow was maintained, and no vessel leakage occurred. In addition, no sheathing of the retinal veins was observed. Optical coherence tomography (OCT) showed a higher intensity for retinal arterioles with sheathing than for normal retinal arterioles. CONCLUSION: Vessel sheathing in our 2 patients (3 eyes) differed from the sheathing seen in vasculitis. Based on the hyperintensity on OCT, this sheathing may have been due to retinal artery calcification induced by hypoxia and inflammation associated with reRD.

Implication of VEGF and aquaporin 4 mediating Müller cell swelling to diabetic retinal edema.

PURPOSE: Aquaporin 4 (AQP4), a water channel protein, is known to be expressed in retinal Müller cells. The purpose of this study was to determine the effects of VEGF and AQP4 channels on the volumetric changes in Müller cells. METHODS: Retinas from diabetic rats and a cultured Müller cell line, TR-MUL5, were used in this study. Intravitreal injections of VEGF or PBS were performed on either streptozotocin (STZ)-induced diabetic or normoglycemic rats. Retinal sections were immunostained for anti-glial fibrillary acidic protein (GFAP), anti-AQP4, and anti-VEGF. VEGF protein levels from collected retinas were determined by western blot analysis. Volumetric changes and nitric oxide (NO) levels in cultured Müller cells were determined using flow cytometry (FACS), in the presence or absence of VEGF and TGN-020, a selective AQP4 inhibitor. RESULTS: In the diabetic rat retina, VEGF immunoreactivity was concentrated in the internal retinal layers, and AQP4 immunoreactivity was higher than controls. The expressions of AQP4 were colocalized with GFAP. Protein levels of VEGF in the hyperglycemic rat retina were significantly higher than controls. FACS analyses showed that exposure to VEGF enlarged Müller cells, while exposure to TGN-020 suppressed the enlargement. Intracellular levels of NO were increased after exposure to VEGF, which was suppressed following the addition of TGN-020. CONCLUSION: The observed Müller cell swelling is mediated by VEGF and AQP4.

Protective effect of P7C3 on retinal ganglion cells from optic nerve injury.

PURPOSE: To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing. METHODS: The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7. The levels of NAD and NAD-related genes were also determined. RESULTS: The density of RGCs was 2009.4 ± 57.7 cells/mm2 in the sham controls; it was significantly lower in the crush-placebo group at 979.7 ± 144.3 cells/mm2 (P < 0.0001). The neuroprotective effects of P7C3-A20 was demonstrated by the significantly higher density of 1266.0 ± 193.1 cells/mm2 than in the crush-placebo group (P = 0.01, Scheffe). After crushing the optic nerve the BAX/Bcl-2 ratio was higher in the optic nerves and retina, application of P7C3-A20 significantly reduced this ratio. P7C3-A20 significantly increased the NAD level in the untouched optic nerves from 1.36 ± 0.05 to 1.59 ± 0.10 nmol/mg protein (P = 0.02, t test). Crushing the optic nerve decreased the level to 1.27 ± 0.21 nmol/mg protein and P7C3-A20 preserved the level at 1.43 ± 0.10 nmol/mg protein. Crushing the optic nerve decreased the mRNA levels of Nampt and Sirt-1 in the optic nerves, while P7C3-A20 significantly restored the levels. CONCLUSIONS: P7C3-A20 can protect RGCs from optic nerve crushing possibly through preserving the NAD levels in the optic nerves.