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.

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.

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.

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.

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.

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.

Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve.

The purpose of this study was to determine whether inhibition of aquaporin 4 (AQP4) is neuroprotective or neurodestructive after crushing the optic nerve of rats. The left optic nerves of rats were crushed, and TGN-020 (5.0 mg/kg, crush TGN-020) or its vehicle (DMSO, crush placebo) was injected intraperitoneally just after the crushing. As controls, the left optic nerves were exposed but not touched in other rats (sham controls). The retinal damages were determined by the density of retinal ganglion cells (RGCs) and the ratio of BAX/Bcl-2 on day 7. The glutamate level in the optic nerve on day 1 after the crushing was determined. The expressions of glutamine synthetase, glutamate-aspartate transporter (GLAST), and AQP4 were determined on day 3 by immunoblotting. The effects of AQP4 inhibition on the glutamate-induced changes of AQP4 expression and on the glutamate uptake were determined for optic nerve astrocytes in culture. The results showed that the density of RGCs was 2040 ± 91.3 cells/mm(2) (n = 6) in the sham control, and it was significantly decreased to 1072 ± 134.3 cells/mm(2) after crushing the optic nerve (P < 0.0001, crush placebo, n = 7; Fisher). An intraperitoneal injection of TGN-020 led to a further significant (P = 0.02, Fisher) decrease of the density of RGCs to 743 ± 371 cells/mm(2) (crush TGN-020, n = 7). The mRNA level of BAX/Bcl-2 ratio was 0.37 ± 0.05 in the sham control (n = 6) which was significantly increased to 0.88 ± 0.10 after crushing the optic nerve (placebo crush, n = 7; P = 0.0001, Scheffe). TGN-020 also significantly increased the BAX/Bcl-2 ratio to 1.29 ± 0.4 (n = 6) from the crush placebo group (P = 0.04, Scheffe). Immunoblotting showed similar changes in the protein levels. The glutamate level in the optic nerve was significantly increased to 53.7 ± 6.0 µM/mg/protein on day 1 (n = 4) from the sham control level of 45.9 ± 3.1 µM/mg/protein (n = 4; P = 0.04, t test). TGN-020 significantly (P < 0.05, Scheffe) depressed the expression of glutamate metabolism-related proteins on day 3. Exposure of cultured optic nerve astrocytes to glutamate (1.0 mM, n = 4) significantly increased the expression of AQP4 (P < 0.001, Scheffe) that was depressed by TGN-020 (100 nM, n = 4). In addition, glutamate uptake was inhibited by TGN-020 at 10 nM or higher. These results indicate that an inhibition of AQP4 enhances the loss of RGCs and retinal damages after crushing the optic nerve. Inhibition of AQP4 impairs glutamate metabolism which may account in part for these neurodestructive events.

Cotton Wool Spots after Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Associated with Central Retinal Vein Occlusion.

PURPOSE: To report a case series, whereby we encountered a transient increase in retinal cotton wool spots (CWS) following anti-vascular endothelial growth factor (anti-VEGF) therapy for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). METHODS: Eighteen eyes were treated with intravitreal aflibercept (IVA), and 5 were treated with intravitreal ranibizumab (IVR). Fundus photographs obtained 1 month after initial IVA or IVR injections were retrospectively evaluated for the presence of CWS. RESULTS: Twenty-one (91.3%) patients had the following systemic diseases: hypertension, diabetes mellitus without retinopathy, dyslipidemia, or chronic renal failure requiring dialysis. One month after treatment, reduced macular edema was observed in 21 (91.3%) eyes. Initial injections facilitated complete resolution in 14 eyes, and CWS gradually became fainter with additional injections. CONCLUSION: Some eyes with CRVO-related macular edema can show a transient increase in CWS after initial anti-VEGF therapy; however, macular edema, retinal hemorrhage, and visual acuity were improved in almost every case.

Treatment of massive subretinal hematoma associated with age-related macular degeneration using vitrectomy with intentional giant tear.

The purpose of this study was to report the surgical outcomes after creating a 120° intentional giant retinal tear for use in removing hemorrhage and subretinal proliferative tissue in patients with polypoidal choroidal vasculopathy (PCV) or age-related macular degeneration (ARMD). This study involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of the lens in phakic eyes, we performed a vitrectomy with artificial posterior vitreous detachment. Subsequently, a 120° intentional giant retinal tear was created in the temporal periphery, the retina was then turned, and the subretinal hemorrhage and proliferative tissue were removed. In order to preserve as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual technique under direct visualization. After stretching the retina by use of perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss of the RPE occurred, the fundus findings and the visual acuity (VA) improved in all patients. In addition, postoperative VA improved to ≥20/50 in 3 eyes in which the macular RPE was preserved. This surgical procedure is an effective treatment for PCV or ARMD patients with extensive subretinal hemorrhage and proliferative tissue.

Comparison of histopathological findings between idiopathic and secondary epiretinal membranes.

To evaluate the histopathological findings of idiopathic and secondary epithelial membranes (ERMs). This study involved 19 ERM cases that underwent pars plana vitrectomy (PPV). ERM specimens were obtained from each patient during PPV and immediately fixed in 10 % formalin. Paraffin sections were stained with hematoxylin eosin (HE) and immunohistochemical analysis was performed with glial fibrillary acidic protein (GFAP), Ki-67, CD34, and nestin antibodies. The 19 ERM cases included 11 idiopathic ERM cases and 8 secondary ERM cases i.e., 2 eyes that underwent PPV for retinal detachment and 6 eyes that underwent PPV for proliferative diabetic retinopathy. HE staining showed that some of the idiopathic ERM specimens consisted of internal limiting membrane. In contrast, numerous invasive cells were observed in the secondary ERM specimens compared to the idiopathic ERM specimens. Immunohistochemical analysis revealed GFAP-positive cells in 4 of the 11 idiopathic ERMs cases, yet no nestin-, Ki-67-, or CD34-positive cells in those cases. In contrast, there were 4 GFAP-positive cases, 2 Ki67-positive cases, 3 CD34-positive cases, and 7 cases including nestin-positive cells. The findings of this study indicate that there are different histological characteristics between idiopathic and secondary ERM and that mature nestin-positive cells in the retina might be related to secondary ERM formation.

Nitric Oxide Increases the Expression of Aquaporin-4 Protein in Rat Optic Nerve Astrocytes through the Cyclic Guanosine Monophosphate/Protein Kinase G Pathway.

AIMS: Nitric oxide (NO) is associated with neuroinflammation in the central nervous system. We determined whether NO increases the expression of aquaporin-4 (AQP4) in optic nerve astrocytes of rats. METHODS: Isolated astrocytes were incubated under normoxic or hypoxic conditions with or without glucose (5.5 mM). The astrocytes were also exposed to different concentrations of S-nitroso-N-acetyl-DL-penicillamine (SNAP, 1.0-100 µM), an NO donor. The expression of AQP4 was determined by Western blot analyses, and NO formation was measured by the Griess reaction. The changes in astrocytic cellular volumes were determined by flow cytometry. RESULTS: Hypoxia and glucose deprivation increased AQP4 expression and NO formation. Inhibition of NO synthetase (NOS) significantly suppressed these changes. SNAP caused a significant increase in AQP4 expression, and the increase was significantly suppressed by carboxy-PTIO, a scavenger of NO. Incubation with 8-Br-cyclic guanosine monophosphate (cGMP) mimicked the effects of SNAP, while the addition of either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; inhibitor of soluble guanylate cyclase) or KT5823 (protein kinase G inhibitor) suppressed the SNAP-induced increase in AQP4 significantly. SNAP also caused a significant increase in astrocytic cellular volume through the AQP4 channels. CONCLUSIONS: NO increased the AQP4 expression of optic nerve astrocytes through the cGMP/protein kinase G pathway and enlarged their volume.

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.

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.

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.

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.