Changes in metamorphopsia in daily life after successful epiretinal membrane surgery and correlation with M-CHARTS score.

To determine the correlation between the changes in metamorphopsia in daily life environment and the M-CHARTS scores after epiretinal membrane (ERM) removal, and to determine the criterion for determining whether clinically significant changes in the metamorphopsia score have occurred in M-CHARTS. We studied 65 eyes undergoing vitrectomy for unilateral ERM. Self-administered questionnaires were used to examine the metamorphopsia in their daily life. The degree of metamorphopsia was determined by M-CHARTS. The receiver operating characteristic curve was used to determine the best predictor of the changes in metamorphopsia in daily life. To determine the reproducibility of the M-CHARTS score, another set of 56 eyes with ERM was tested twice on two different days. The postoperative changes in the logarithm of the M-CHARTS score was defined as M2-value. The area under the receiver operating characteristic curve for the M2-value as a predictor of the changes in metamorphopsia in daily life was larger than area under the receiver operating characteristic curve obtained for any other parameter. The optimal cutoff value was -0.4. The 95% limits of agreement between test and retest measurements had a reproducibility of ±0.3 logarithm of the M-CHARTS score. Taking into account not only the reproducibility but also the consistency with the subjective changes, we determined the criterion for clinically significant changes in the M-CHARTS scores as a change of the M2-value by ≥0.4. Evaluating the changes in the M-CHARTS scores in logarithmic form is favorable not only theoretically but also from the perspective of consistency with the subjective changes.


Severe fungal sclerokeratitis caused by Metarhizium anisopliae: a case report and literature review.

To date, there has been only one published report on the infectious sclerokeratitis caused by Metarhizium anisopliae, which is an entomopathogenic fungus. Regarding corneal infection, three reports have been published to date. Although the prognoses of the corneal infections are favourable, prognosis when scleral infection is involved is very poor. A 76-year-old patient presented with foreign body sensation in the left eye. Microscopic examination with Fungi Flora Y staining of the corneal scraping revealed fungal infection. The conjunctiva was melted by the infection over a wide area. Although intensive medications were administered, an emergency surgery was necessary because scleral thinning, corneal perforation and lens prolapse occurred. The fungal isolate was identified as M. anisopliae by sequencing the internal transcribed spacer region. Herein, we report the second known case worldwide of M. anisopliae sclerokeratitis, and we review the literature related to the ocular infections.


Case of adult-onset Coats' disease with epiretinal membrane treated with 25-gauge pars plana vitrectomy.

We describe a case of untreated adult-onset Coats' disease with a proliferative epiretinal membrane (ERM) treated successfully with 25-gauge pars plana vitrectomy (25GPPV). A 26-year-old man presented with a 3-week history of decreased vision in his left eye. At the initial examination, the decimal best-corrected visual acuity (BCVA) was 0.7 in the left eye. Ophthalmoscopy revealed the typical appearance of Stage 2A Coats' disease but with a proliferative ERM in the posterior pole. The patient received 2 monthly intravitreal injections of 2.5 mg bevacizumab, 5 laser photocoagulations to the area of telangiectasia, and 1 session of cryoretinopexy. Nine months after the initial visit, a traction by the ERM on the parafoveal area developed causing macular edema which reduced the BCVA to 0.3. He underwent 25GPPV with the removal of the ERM. In addition, the peripheral telangiectasia was treated intraoperatively with both laser photocoagulation and cryoretinopexy. Postoperatively, the traction to the parafoveal area was released and the BCVA improved to 0.6 which remained stable during the follow-up period of 13 months. We conclude that 25GPPV combined with ERM peeling, laser photocoagulation, and cryoretinopexy can be effective for adult-onset Coats' disease associated with an ERM.

The Journal of Medical Investigation : JMI


A case of endogenous endophthalmitis due to Listeria monocytogenes

Japanese Journal of Clinical Ophthalmology


Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy.

PPAR may play an important role in the pathogenesis of PDR.

Journal of Diabetes and its Complications


Relationship between retinal microstructures and visual acuity after cataract surgery in patients with retinitis pigmentosa.

To study the relationship between the retinal microstructures and the best-corrected visual acuity (BCVA) after cataract surgery in patients with retinitis pigmentosa (RP). 58 eyes of 43 consecutive RP patients who underwent cataract surgery were studied. The BCVA was measured before and 3 months after the surgery. The appearance of the inner segment/outer segment (IS/OS) line of the photoreceptors in the optical coherence tomographic (OCT) images at the fovea was graded; Grade 1, IS/OS line not visible; Grade 2, IS/OS line abnormal or discontinuous; and Grade 3, IS/OS line normal. The central foveal thickness (CFT) and the length of the IS/OS line were measured in the spectral-domain OCT images. The postoperative BCVAs in logMAR units (Grade 1, 1.04±0.36; Grade 2, 0.33±0.16; Grade 3, 0.08±0.14) and the improvements in the BCVA in logMAR units (Grade 1, 0.22±0.28; Grade 2, 0.53±0.48; Grade 3, 0.54±0.35) were significantly different among Grade 1, 2 and 3 groups (p<0.0001, p=0.0378; respectively). A postoperative BCVA of <0.2 logMAR units was achieved in 0% in Grade 1, 20% in Grade 2 and 74% in Grade 3 (p<0.0001). There was a significant correlation between the postoperative BCVA and the length of the IS/OS line (r=-0.601 p<0.0001) or the CFT (r=-0.510, p<0.0001). The presence of normal IS/OS line in the OCT images is associated with good visual recovery after cataract surgery in RP patients. The integrity of the IS/OS line may be important for predicting good postoperative BCVA.


Polymicrobial Sclerokeratitis Caused by Scedosporium apiospermum and Aspergillus cibarius.

The aim of this study was to report the first case of polymicrobial fungal sclerokeratitis caused by infection with both Scedosporium apiospermum and Aspergillus cibarius, and notify the medical community of the possibility of infection caused by A. cibarius in humans. A 78-year-old woman presented to a medical practitioner with epiphora and a purulent discharge in her left eye. After concurrent administration of topical antibiotics and systemic steroids, her symptoms worsened, and she was referred to the Tokushima University Hospital. Because of suspected fungal infection, microscopic examination and cultivation of both corneal and scleral scrapings were performed. Fungi were observed on microscopic examination, and S. apiospermum was isolated only from the sclera in the early stage of the clinical course. Although administration of an adequate medication regimen comprising topical and systemic antifungal drugs resulted in an improvement in the sclera, keratitis persisted, and the infected sclera was melted. After scleral transplantation, administration of systemic caspofungin and high concentrations of voriconazole solution eye drops resulted in a gradual improvement in keratitis. A strain of filamentous fungus was isolated from the cornea 6 weeks after the cultivation on a Sabouraud agar plate, and it was identified as A. cibarius. A. cibarius may infect human tissue. Coinfection of the cornea and the sclera with 2 different species of fungi is likely to follow a complex clinical course.


Renin-angiotensin system regulates neurodegeneration in a mouse model of normal tension glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). In the present study, we found that expressions of angiotensin II type 1 receptor (AT1-R) and Toll-like receptor 4 (TLR4) are increased in RGCs and retinal Müller glia in EAAC1-deficient (KO) mice. The orally active AT1-R antagonist candesartan suppressed TLR4 and lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expressions in the EAAC1 KO mouse retina. Sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with candesartan was effective for RGC protection in EAAC1 KO mice without affecting IOP. In cultured Müller glia, candesartan suppressed LPS-induced iNOS production by inhibiting the TLR4-apoptosis signal-regulating kinase 1 pathway. These results suggest that the renin-angiotensin system is involved in the innate immune responses in both neural and glial cells, which accelerate neural cell death. Our findings raise intriguing possibilities for the management of glaucoma by utilizing widely prescribed drugs for the treatment of high blood pressure, in combination with conventional treatments to lower IOP.


Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma.

Glaucoma is one of the leading causes of irreversible blindness that is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). Brimonidine (BMD) is an α2-adrenergic receptor agonist and it is commonly used in a form of eye drops to lower IOP in glaucoma patients. Recent studies have suggested that BMD has direct protective effects on RGCs involving IOP-independent mechanisms, but it is still controversial. In the present study, we examined the effects of BMD in EAAC1-deficient (KO) mice, an animal model of normal tension glaucoma. BMD caused a small decrease in IOP, but sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with BMD was highly effective for RGC protection in EAAC1 KO mice. BMD suppressed the phosphorylation of the N-methyl-D-aspartate receptor 2B (NR2B) subunit in RGCs in EAAC1 KO mice. Furthermore, in cultured Müller glia, BMD stimulated the production of several neurotrophic factors that enhance RGC survival. These results suggest that, in addition to lowering IOP, BMD prevents glaucomatous retinal degeneration by stimulating multiple pathways including glia-neuron interactions.


Ineffectiveness of intrastromal voriconazole for filamentous fungal keratitis.

The purpose of this study is to describe the ineffectiveness of intrastromal voriconazole injection for filamentous fungal keratitis by contrasting the effectiveness for yeast keratitis. We examined seven fungal keratitis patients prospectively. All yeast was identified by molecular phylogenetic analyses of the chromosomal regions coding for the D1/D2 domain of the large-subunit 26S ribosomal RNA gene. All filamentous fungi were identified by the sequencing of internal transcribed spacers of the ribosomal DNA gene regions. Approximately 0.1 mL of voriconazole diluted with saline to 1.0% was injected with a 30-gauge needle inserted obliquely into the three to five clear cornea sites around the abscess. All subjects were administered natamycin ointment and oral itraconazole. When needed, intravenous micafungin, voriconazole, and/or intracameral voriconazole were added. Clinical courses were observed by the slit lamp microscope. Histopathology was examined when the corneas were removed. All cases that were caused by yeast healed quickly after injections. Two cases of keratitis caused by Fusarium, and one case caused by Aspergillus, did not heal completely. In the Fusarium cases, additional antifungal medications (3.0% topical voriconazole and intravenous injection of micafungin) were needed. After optical penetrating keratoplasty in one of the cases, fungi were found in the deep stroma of the removed cornea. In the case of Aspergillus keratitis, pathological findings also showed fungi deep in the stroma of the removed cornea and the keratitis recurred after therapeutic penetrating keratoplasty. Intrastromal voriconazole injection is successful in treating yeast keratitis. However this is not the case for filamentous fungal keratitis.


A case of head tilt due to orbital floor fracture

斜頚をきたした眼窩下壁骨折の小児例

Folia japonica de ophthalmologica clinica


Pneumatic displacement with intravitreal bevacizumab for massive submacular hemorrhage due to polypoidal choroidal vasculopathy.

The purpose of this study was to compare the effectiveness of pneumatic displacement combined with intravitreal bevacizumab (IVB) with that of pneumatic displacement (PD) alone to treat massive submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). Thirty-two eyes of 32 patients with massive SMH secondary to PCV were studied. Twenty-two eyes were treated with a combination of PD and 1.25 mg of intravitreal bevacizumab (PD + IVB group), and ten eyes with pneumatic displacement alone (PD group). Pretreatment, the differences in best-corrected visual acuity and size of the SMH between the two groups were not significant (P=0.59 and P=0.72, respectively). Complete displacement of the hemorrhage from under the fovea was achieved in 19 of 22 eyes (86.4%) in the PD + IVB group and in five of ten eyes (50%) in the PD group. The best-corrected visual acuity in the PD + IVB group was significantly better than that in the PD group at one, 3, and 6 months after treatment (P<0.001, P<0.001, and P<0.001, respectively). Improvement in best-corrected visual acuity by >0.3 logMAR units was obtained in 18 eyes (81.8%) in the PD + IVB group and two eyes (20%) in the PD group (P<0.001). The number of eyes that required additional treatments was significantly fewer in the PD + IVB group than in the PD group (P=0.0001). The combination of PD and IVB may be a better therapeutic procedure for eyes with massive SMH due to PCV in the short term because of the better visual outcome and less need for additional treatments.


Changes of fundus autofluorescence and spectral-domain optical coherence tomographic findings after treatment of primary intraocular lymphoma.

We report the fundus autofluorescence (FAF), spectral-domain optical coherence tomographic (SD-OCT), microperimetric, and multifocal electroretinographic (mfERG) findings before, during, and after successful treatment of a primary intraocular lymphoma (PIOL). A 57-year-old man had biopsy-proven PIOL in his left eye, and he was treated with intravitreal methotrexate injections for 8 months. Before treatment, fundus examination disclosed many small, yellow lesions with distinct boundaries in the posterior fundus which became atrophic 9 months after the initial treatment. FAF showed a pattern of granular hypoautofluorescence and hyperautofluorescence before the treatments and patchy hypoautofluorescence corresponding to retinal pigment epithelial (RPE) atrophy after the treatments. SD-OCT showed increased nodularity at the level of and above the RPE, a separation of Bruch membrane from the RPE, partial damage of the RPE, disruption of the photoreceptor inner segment/outer segment (IS/OS) junction, multiple hyperreflective signals in the inner retina, foveal thinning, and parafoveal thickening. After treatment, the hyperreflective infiltrations in the inner retina were markedly decreased, and the RPE and IS/OS junction were restored. The foveal thinning and parafoveal thickening resolved, and the central choroidal thickness decreased. During the follow-up, the mfERGs remained decreased. In contrast, microperimetry showed a partial improvement of the retinal sensitivity. FAF and SD-OCT are useful noninvasive methods to evaluate the retinal and choroidal changes before and after treatment of PIOL. Our results suggest that visual recovery after successful treatment may be limited once macula is infiltrated.

Journal of Ophthalmic Inflammation and Infection


Spectral-domain optical coherence tomographic and fundus autofluorescence findings in eyes with primary intraocular lymphoma.

The purpose of this study was to evaluate the findings on spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) in three eyes with primary intraocular lymphoma (PIOL). The medical records of three eyes from three patients with biopsy-proven PIOL and retinal infiltrations were reviewed. The SD-OCT and fluorescein angiographic findings were evaluated in the three eyes and FAF images in two eyes. The PIOL in the three patients was monocular. Vitreous opacities and retinal infiltrations were observed in the three eyes, and iritis was present in two eyes. The cytologic diagnosis was class V in two eyes and class III in one eye. The interleukin-10/interleukin-6 ratio was >1.0 in the vitreous and aqueous humor of the three eyes. The FAF images for two eyes showed abnormal granular hyperautofluorescence and hypoautofluorescence which were the reverse of the pattern in the fluorescein angiographic images. In all three eyes, SD-OCT showed hyper-reflective infiltrations at the level of the retinal pigment epithelium (RPE), a separation of the Bruch membrane from the RPE, damage to the RPE, disruption of the photoreceptor inner segment/outer segment junction, and multiple hyper-reflective signals in the inner retina. Because of the characteristic FAF and SD-OCT findings in these eyes with PIOL, we suggest that these noninvasive methods may be used for a rapid diagnosis of PIOL and also for understanding the pathology of PIOL.


Methicillin-Resistant Staphylococcus aureus Keratitis after Descemet's Stripping Automated Endothelial Keratoplasty.

We report a case of methicillin-resistant Staphylococcus aureus (MRSA) keratitis after Descemet's stripping automated endothelial keratoplasty (DSAEK). An 87-year-old woman who had undergone a DSAEK 4 months previously was referred to Tokushima University Hospital with a diagnosis of infectious keratitis after DSAEK. A white abscess and infiltration in the inferior cornea of the right eye were observed. We started an empiric therapy using topical levofloxacin and chloramphenicol on the basis of the microscopic findings of the corneal scraping concurrently with cultivation of the cornea. A strain of MRSA was isolated from the corneal sample. Although the strain was susceptible to chloramphenicol, it was resistant to quinolone. The keratitis improved rapidly due to empiric therapy, and topical steroids could be resumed 6 days after initiation of the empiric therapy. To our knowledge, this is the first case of MRSA keratitis, and the second case of bacterial keratitis, after DSAEK. MRSA keratitis can occur following uneventful DSAEK. The empiric therapy on the basis of results from a light microscopic examination of a Gram-stained corneal scraping and restarting topical steroids in the early stages of medication contributed to the good clinical course of this case.


Infectious conjunctivitis caused by Pseudomonas aeruginosa isolated from a bathroom.

The elucidation of the routes of transmission of a pathogen is crucial for the prevention of infectious diseases caused by bacteria that are not a resident in human tissue. The purpose of this report is to describe a case of suture-related conjunctivitis caused by Pseudomonas aeruginosa for which we identified the transmission route using pulsed-field gel electrophoresis (PFGE). A 38-year-old man, who had undergone surgery for glaucoma 2 years ago previously, presented with redness, discomfort, and mucopurulent discharge in the right eye. A 9-0 silk suture had been left on the conjunctiva. A strain of P. aeruginosa was isolated from a culture obtained from the suture, and the patient was therefore diagnosed with suture-related conjunctivitis caused by P. aeruginosa. The conjunctivitis was cured by the application of an antimicrobial ophthalmic solution and removal of the suture. We used PFGE to survey of the indoor and outdoor environments around the patient's house and office in order to elucidate the route of transmission of the infection. Three strains of P. aeruginosa were isolated from the patient's indoor environment, and the isolate obtained from the patient's bathroom was identical to that from the suture. The case highlights the fact that an indoor environmental strain of P. aeruginosa can cause ocular infections.


Outcome of Vogt-Koyanagi-Harada disease as related to clinical types

Vogt-小柳-原田病の病型と予後の検討

Japanese Journal of Clinical Ophthalmology


Photoreceptor impairment and restoration on optical coherence tomographic image.

With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.


A case of early-onset sarcoidosis and Blau syndrome

若年発症サルコイドーシス/Blau症候群の1例


Panretinal photocoagulation with simultaneous cryoretinopexy or intravitreal bevacizumab for neovascular glaucoma.

To compare the therapeutic effects of panretinal photocoagulation (PRP) combined with intravitreal bevacizumab (IVB) and cryoretinopexy (CR-IVB) to that of PRP combined with IVB alone in eyes with neovascular glaucoma (NVG). Retrospective, consecutive, case-control study. The medical records of 102 eyes of 96 patients with NVG due to proliferative diabetic retinopathy, central retinal vein occlusion, and ocular ischemic syndrome were reviewed. The mean age of the patients was 59.6 ± 11.5 years, with a range of 34 to 84 years. Patients received either 1.25 mg/0.05 ml of IVB combined with 360° of cryotherapy of the peripheral retina (CR-IVB subgroup) or IVB alone (IVB alone subgroup) as adjunctive treatments to PRP. The patients were followed for at least 12 months. Fifty-four eyes of 49 patients had open-angle NVG; 30 of these eyes were treated by CR-IVB, and 24 eyes by IVB alone. Forty-eight eyes of 48 patients had angle-closure NVG; 22 of these eyes were treated by CR-IVB, and 26 eyes were by IVB alone. Failure was defined as a postoperative intraocular pressure (IOP) >21 mmHg for two consecutive follow-up visits, or the need of additional surgery such as trabeculectomy or diode laser cycloablation. The differences in the success rates between the CR-IVB and IVB alone subgroups for the eyes with open-angle and closed-angle NVG were compared. The success rate at 12 months in eyes with open-angle NVG was 80.0% in the CR-IVB subgroup and 41.7% in the IVB alone subgroup (P = 0.0096). In eyes with angle-closure NVG, the success rate at 12 months was 22.7% in the CR-IVB subgroup and 0% in the IVB-alone subgroup (P = 0.030). The significantly better IOP control after PRP combined with cryotherapy and IVB than after PRP with IVB alone indicates that cryotherapy enhances the effectiveness of PRP for neovascular glaucoma for at least 1 year.

Graefe's Archive for Clinical and Experimental Ophthalmology


Photoreceptor impairment on optical coherence tomographic images in patients with retinitis pigmentosa.


Expression of promyelocytic leukemia protein and vascular endothelial growth factor in aqueous humor and vitreous fluid in patients with proliferative diabetic retinopathy.

To examine the expression of promyelocytic leukemia protein (PML) in the eye of proliferative diabetic retinopathy (PDR) patients. PML mRNA levels were measured in proliferative membranes from 12 PDR patients and idiopathic epiretinal membranes from 5 control patients by quantitative RT-PCR. Protein levels of PML and vascular endothelial growth factor (VEGF) in aqueous humor and vitreous fluid samples from 34 PDR patients and 38 control patients were determined using ELISA. The PML mRNA expression levels in membrane samples, and the PML protein concentrations in aqueous humor and vitreous fluid samples were significantly lower in PDR patients than control patients. We observed a statistically significant inverse correlation between the concentrations of PML and VEGF in the aqueous humor and vitreous fluid of PDR patients. PML may be a good candidate as a diagnostic marker and a therapeutic agent for PDR.


Quantitative analysis of cystoid macular edema using scanning laser ophthalmoscope in modified dark-field imaging.

To quantitatively analyze cystoid macular edema (CME) using scanning laser ophthalmoscope in the modified dark-field imaging. We studied 37 eyes with CME associated with different diseases before and after treatment. The CME area was measured with the modified dark-field imaging and fluorescein angiography. The best-corrected visual acuity, mean deviation and macular sensitivity measured by Humphrey automated perimetry, and foveal thickness and macular volume determined by optical coherence tomography were investigated. The CME area could be clearly outlined in 50% with the fluorescein angiography and in 100% with the modified dark-field imaging (P < 0.0001). The CME area calculated using the modified dark-field imaging was significantly correlated with that using the fluorescein angiography (P = 0.0001). Before treatment, the CME area calculated using the modified dark-field imaging was significantly correlated with only the macular volume (P = 0.0230). Three months after treatment, decrease in the CME area was significantly correlated with improvement in the best-corrected visual acuity, mean deviation, macular sensitivity, foveal thickness, and macular volume (P < 0.05 for all). Our findings indicate that scanning laser ophthalmoscope in the modified dark-field imaging can measure the CME area and is useful in analyzing CME quantitatively. The findings can also be used to evaluate the effectiveness of treatment.


Descemet-stripping automated endothelial keratoplasty for vitrectomized cases with traumatic aniridia and aphakic bullous keratopathy.

The surgical indication for Descemet-stripping automated endothelial keratoplasty (DSAEK) is largely limited to phakic or pseudophakic cases of endothelial dysfunction with normal pupils, because the endothelial lenticule is generally attached to the recipient cornea by use of gas tamponade into the anterior chamber. Although it may be desirable for vitrectomized cases with aniridia and aphakic bullous keratopathy without capsule support to undergo DSAEK, one of the major problems is lenticule detachment during surgery or in the postoperative period. To perform DSAEK in such cases, special surgical techniques are needed in order to facilitate adhesion of the lenticule. Herein, we describe a suture technique for attaching the endothelial lenticule in DSAEK for aniridic and aphakic cases that have undergone vitrectomy for traumatic vitreoretinal disease.


Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury.

Optic nerve injury (ONI) induces retinal ganglion cell (RGC) death and optic nerve atrophy that lead to visual loss. Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced RGC apoptosis. In this study, we found that ONI-induced p38 activation and RGC loss were suppressed in ASK1-deficient mice. Sequential in vivo retinal imaging revealed that post-ONI treatment with a p38 inhibitor into the eyeball was effective for RGC protection. ONI-induced monocyte chemotactic protein-1 production in RGCs and microglial accumulation around RGCs were suppressed in ASK1-deficient mice. In addition, the productions of tumor necrosis factor and inducible nitric oxide synthase in microglia were decreased when the ASK1-p38 pathway was blocked. These results suggest that ASK1 activation in both neural and glial cells is involved in neural cell death, and that pharmacological interruption of ASK1-p38 pathways could be beneficial in the treatment of ONI.


A Case of Delayed-Onset Propionibacterium acnes Endophthalmitis after Cataract Surgery with Implantation of a Preloaded Intraocular Lens.

To report a case of delayed-onset endophthalmitis after implantation of a preloaded intraocular lens (IOL) and examine the surgically removed IOL by scanning electron microscopy (SEM). A 77-year-old female underwent uneventful phacoemulsification and aspiration with preloaded silicone IOL implantation. Since intraocular inflammation unexpectedly worsened 1 month after the surgery, she was referred to our hospital. Her visual acuity was hand motion in the left eye. Hypopyon and fibrin formation were observed in the anterior chamber. A diagnosis of postoperative delayed-onset endophthalmitis was made, and vitrectomy with anterior chamber wash-out was performed. As intraocular inflammation remained unchanged postoperatively, an additional surgery with IOL removal was performed. We cultivated the surgically removed samples of aqueous humor and vitreous fluid under both aerobic and anaerobic conditions, performed 16S rDNA clone library analysis of these clinical samples, and examined the removed IOL by SEM. Inflammation subsided after the re-operation. Although cultures of aqueous and vitreous samples were negative, DNA of Propionibacterium acnes was detected in the aqueous humor. The SEM images showed that the rod bacteria and biofilm-like material formed on the tip of the IOL haptic. Delayed-onset endophthalmitis may occur after uneventful implantation of a preloaded IOL. The SEM findings suggested that the tip of the preloaded IOL haptic might scratch bacteria which adhered to the tip of the injector nozzle when the IOL was inserted into the anterior chamber. In some cases with delayed-onset endophthalmitis, IOL removal is needed to eliminate the bacteria which adhere to the tip of the IOL haptic.


Choroidal folds in a case of acute posterior multifocal placoid pigment epitheliopathy

脈絡膜趨壁が観察された急性後部多発性斑状色素上皮症の1例

Japanese Journal of Clinical Ophthalmology


Time course of changes in metamorphopsia, visual acuity, and OCT parameters after successful epiretinal membrane surgery.

To follow the changes in the metamorphopsia, visual acuity, and OCT parameters after epiretinal membrane (ERM) removal. The study included 49 eyes of 49 patients with an ERM who underwent vitrectomy and membrane peeling. The changes in the best-corrected visual acuity (BCVA), metamorphopsia, and central foveal thickness (CFT) were evaluated at baseline and 1, 3, 6, 9, and 12 months postoperatively. M-CHARTS were used to quantify metamorphopsia. The mean BCVA, metamorphopsia scores for horizontal lines (MH) and vertical lines (MV), and CFT improved significantly at 12 months after surgery (P < 0.001). The baseline BCVA, MH score, and MV score were significantly correlated with the corresponding BCVA, MH score, and MV score at 12 months after surgery (P < 0.01). The MH and MV scores at 12 months was significantly correlated with the BCVA at 12 months (P < 0.01), and the baseline MV score was significantly correlated with the BCVA at 12 months (P < 0.05). The MH score but not the MV score was significantly correlated with the CFT at baseline and 12 months (P < 0.05). The preoperative BCVA, MH score, and MV score were prognostic factors for the corresponding postoperative BCVA, MH score, and MV score. These results suggest that surgery for ERM should be considered before severe reduction in the BCVA or the degree of metamorphopsia. In addition, the preoperative MV score was a prognostic factor for postoperative BCVA. The MH score but not the MV score was correlated with the CFT preoperatively and postoperatively.

Investigative Ophthalmology & Visual Science


網膜静脈周囲炎が顕著であったmultiple evanescent white dot syndromeの小児例


Aggressive retinal astrocytoma associated with tuberous sclerosis.

We report the case of a patient with an aggressive retinal astrocytoma accompanied with macular edema and neovascular vessels, who was initially treated with intravitreal bevacizumab injections. A 24-year-old male presented to our clinic complaining of visual disturbance in his right eye. At 8 years of age, he had been diagnosed as having tuberous sclerosis complex. Fundus examination demonstrated a retinal tumor accompanied with marked neovascular vessels on the surface, retinal hemorrhage, and macular edema. After six monthly intravitreal bevacizumab injections, fundus examination demonstrated marked regression of the macular edema and neovascular vessels. Two months later, a vitreous hemorrhage developed which necessitated pars plana vitrectomy. After additional intravitreal bevacizumab injection for preventing intraoperative bleeding, vitrectomy with endophotocoagulation for the tumor was performed. The vitreous sample was obtained during vitrectomy, and we measured the vascular endothelial growth factor concentration by enzyme-linked immunosorbent assay. The surgically removed epiretinal neovascular membrane and biopsied retinal tumor expressed vascular endothelial growth factor, although several intravitreal bevacizumab injections led to a vitreous vascular endothelial growth factor concentration of undetectable levels. The clinical course and immunohistochemical analyses indicate that intravitreal bevacizumab monotherapy may have been insufficient to treat the aggressive retinal astrocytoma with macular edema and that laser photocoagulation or photodynamic therapy for the tumor should be considered following intravitreal bevacizumab injection in such cases.


Two cases of focal choroidal excavation detected by spectral-domain optical coherence tomography.

To report the clinical findings of 2 patients with focal choroidal excavation in the macula detected by spectral-domain optical coherence tomography (SD-OCT). Three eyes of 2 patients with a focal macular choroidal excavation detected by SD-OCT were studied. The eyes were examined by fundus autofluorescence (FAF), fluorescein angiography, fundus-related microperimetry, and multifocal electroretinography (mfERG). In spite of a complaint of metamorphopsia, the visual acuity was normal in 2 eyes. SD-OCT demonstrated a choroidal excavation in the macula but the foveal contour was normal in 3 eyes. The excavation involved the outer retinal layers up to the external limiting membrane in all eyes, and a type 2 secondary choroidal neovascularization (CNV) developed in 1 of the 3 eyes. There were areas of hypoautofluorescence in the FAF images, and areas of decreased retinal sensitivity determined by microperimetry. These areas corresponded to the choroidal excavation in all eyes. The P1 amplitudes of the mfERGs were decreased in the fovea of 1 eye without a CNV. The choroidal excavation remained stable for 3 years in 2 eyes, a secondary CNV developed in 1 eye during the course of the disease. More cases and longer follow-up periods will be necessary to determine the etiology, clinical course, and visual prognosis of eyes with a choroidal excavation.


Macular Ischemia Following Intravitreal Bevacizumab Therapy for Diabetic Macular Edema

糖尿病黄斑浮腫に対するベバシズマブ硝子体内投与後の黄斑虚血

To examine the effects of macular ischemia after intravitreal bevacizumab (IVB) in patients with diabetic macular edema(DME). Thirty-three eyes of 33 patients with DME were treated with IVB. Fluorescein angiography (FA) was conducted before and 3 months after IVB, the pretreatment sizes of the foveal avascular zone (FAZ) calculated by FA were compared to the values at 3 months after IVB. This study was approved by the Chiba University Hospital Clinical Research Ethics Committee. After IVB, the size of the FAZ enlarged significantly (p = 0.03). Among the 33 patients treated with IVB, 2 patients (6%) had advanced macular ischemia with an FAZ enlarged by 50% or more. In both patients, the visual acuity did not worsen and the foveal thickness decreased. It is possible that IVB led to macular ischemia.

Acta Societatis Ophthalmologicae Japonicae


Twenty five-gauge sutureless vitrectomy versus 20-gauge vitrectomy in epiretinal membrane surgery.

To compare visual outcomes, intraoperative and postoperative complications of 25-gauge transconjunctival sutureless vitrectomy (25-G TSV) versus conventional 20-gauge vitrectomy in epiretinal membrane (ERM) surgery. A retrospective comparative study was conducted on 200 eyes with idiopathic ERM who underwent either primary 20-gauge vitrectomy (n=95) or 25-G TSV (n=105) with 6 months follow up. The following parameters were collected and compared: age, gender, best corrected visual acuity (BCVA), intraocular pressure (IOP), postoperative anterior chamber inflammation, intraoperative and postoperative complications. Twenty-five gauge group achieved a significantly better vision at the 1(st) postoperative month (p=0.008) and a significantly higher incidence of visual improvement 6 months postoperatively (p=0.04) than 20-gauge group. Intraocular pressure was significantly higher at the 1(st), 3(rd) and 6(th) postoperative months compared with baseline in the 20-G group. However, in the 25-gauge group IOP remained near to the baseline at the same period. Twenty five-gauge group achieved a significantly lower anterior chamber inflammation and a lower incidence of postoperative cystoid macular edema (CME) (p=0.01), hyphema (p=0.000) and after cataract (p=0.000) than 20-gauge group. The 25-gauge sutureless vitrectomy achieves rapid and higher visual improvement, less postoperative inflammation and complications than the 20-gauge vitrectomy in ERM surgery.

The Journal of Medical Investigation : JMI


Ocular findings following discontinuation of oral pilocarpine in patients with dry eye

ドライアイ患者におけるピロカルピン塩酸塩服用中止後の眼所見


Efficacy of the Quickert procedure for involutional entropion: the first case series in Asia.

To report the efficacy of the Quickert procedure in the first case series of involutional entropion in an elderly Asian population, and to introduce the technique to Asian ophthalmologists including general ophthalmologisits and ophthalmic trainees. We conducted a retrospective review of 13 consecutive patients underwent the Quickert procedure for involutional entropion by occasional eyelid surgeons at Tokushima University Hospital or Mino Tanaka Hospital from September 2003 to April 2010. Demographic data, including gender, age, history of previous eyelid surgery, systemic disease, recurrence of entropion, postoperative complications, and symptoms were analyzed. There were 5 male (38.5%) and 8 female (61.5%) subjects with a mean age of 77.8 years. Three patients underwent previous surgery for entropion were included. Entropion was rectified in all patients by a single Quickert procedure, and no recurrence was observed for a maximum of 89 months after the surgery. Although notching of the eyelid margin and mild symblepharon were observed in one patient, no symptoms associated with these complications were reported. The Quickert procedure can be one of the surgical procedures of choice for involutional entropion and should be common surgical approach for occasional eyelid surgeons in Asia as well as in western countries.


Diagnostic imaging in patients with retinitis pigmentosa.

Retinitis pigmentosa (RP) is a progressive inherited retinal disease, and patients with RP have reduced visual function caused by a degeneration of the photoreceptors and retinal pigment epithelium (RPE). At the end stage of RP, the degeneration of the photoreceptors in the fovea reduces central vision, and RP is one of the main causes of acquired blindness in developed countries. Therefore, morphological and functional assessments of the photoreceptors in the macula area can be useful in estimating the residual retinal function in RP patients. Optical coherence tomography (OCT) is a well-established method of examining the retinal architecture in situ. The photoreceptor inner/outer segment (IS/OS) junction is observed as a distinct, highly reflective line by OCT. The presence of the IS/OS junction in the OCT images is essential for normal visual function. Fundus autofluorescence (FAF) results from the accumulation of lipofuscin in the RPE cells and has been used to investigate RPE and retinal function. More than one-half of RP patients have an abnormally high density parafoveal FAF ring (AF ring). The AF ring represents the border between functional and dysfunctional retina. In this review, we shall summarize recent progress on diagnostic imaging in eyes with RP.


Vitreous biopsy for the diagnosis of intraocular lymphoma in twenty-three eyes

眼内悪性リンパ腫の鑑別のため硝子体生検を施行した21例の検討

Japanese Journal of Clinical Ophthalmology


Long-term therapeutic efficacy of the subthreshold micropulse diode laser photocoagulation for diabetic macular edema.

Our results indicate that SMDLP has a beneficial effect on DME. However, prospective studies are needed to evaluate this technique in more detail.

The mean foveal thickness was 504 μm before the SMDLP, and it was significantly reduced to 439 μm at 1 month (P = 0.001), 409 μm at 3 months (P < 0.0001), 358 μm at 6 months (P < 0.0001), and 320 μm at 12 months (P < 0.0001). The mean BCVA at baseline was 0.47 logarithm of the minimal angle of resolution (logMAR) units, and it was not changed significantly at all of the postoperative examinations. Among the 56 eyes, 10 (17.8%) had an improvement of BCVA of >0.2 logMAR units, 36 (64.2%) remained the same, and 10 eyes (17.8%) had a reduction of >0.2 logMAR units at 12 months postoperatively.


Foveal microstructure on spectral-domain optical coherence tomographic images and visual function after macular hole surgery.

To determine the correlation between the recovery of foveal microstructure and the visual acuity or the foveal sensitivity after idiopathic macular hole (MH) closure. Prospective, consecutive, observational case series. We studied 43 eyes of 43 patients before and 1, 3, and 6 months after MH surgery. The best-corrected visual acuity (BCVA), the foveal sensitivity measured by MP1 microperimetry, and the photoreceptor inner and outer segment (IS/OS) junction and the external limiting membrane (ELM) determined by spectral-domain optical coherence tomography were investigated. Preoperatively, the lengths of the IS/OS junction defect and the ELM defect were significantly correlated with only the foveal sensitivity (P<.0001). At all postoperative times, the lengths of both the IS/OS and ELM defects were significantly correlated with both the BCVA and the foveal sensitivity (P<.05 for all). The preoperative lengths of both the IS/OS and ELM defects were significantly correlated with the foveal sensitivity at 6 months after surgery (P=.0022, P=.0031, respectively). The IS/OS junction defect was significantly correlated with the ELM defect at all times (P<.0001 for all). No restoration of the IS/OS junction was observed in eyes without the ELM restoration. The restoration of the ELM is closely associated with that of the IS/OS junction. The preoperative IS/OS or ELM defect was associated with the postoperative foveal sensitivity. The restoration of not only the IS/OS junction but also the ELM may reflect the morphologic and functional recovery of the foveal photoreceptors in surgically closed MHs.


Clinical features of optic neuritis positive for anti-aquaporin 4 antibody

抗アクアポリン4抗体陽性視神経炎の臨床像 (特集 第64回日本臨床眼科学会講演集(2))


Macular abnormalities in patients with retinitis pigmentosa: prevalence on OCT examination and outcomes of vitreoretinal surgery.

Abstract. Purpose: To determine the prevalence of macular abnormalities detected by optical coherence tomography (OCT) in patients with retinitis pigmentosa (RP), and to report the results of pars plana vitrectomy (PPV) in five patients with RP. Methods: OCT images of the macula of 622 eyes of 323 patients with RP were evaluated. All patients had a complete clinical examination, and PPV was performed on two RP patients with a macular hole (MH), two patients with vitreomacular traction (VMT) syndrome, and one patient with cystoid macular oedema (CME). Results: A macular lesion was detected by OCT in 46 eyes (7.4%) of 37 patients (11.5%). CME was detected in 34 eyes (5.5%) of 26 patients, an epiretinal membrane in four eyes of four patients, VMT in five eyes of four patients, and full-thickness MH in three eyes of three patients. PPV was performed on five of these eyes. The MH was closed with vision improvement after a single surgery in one eye, and was closed after repeated PPVs with a decrease of vision in another eye. In both patients with VMT, the visual acuity decreased after the surgery. The macular morphology and visual acuity did not improve postoperatively on the one patient with CME who underwent PPV. Conclusion: When OCT is used, macular abnormalities are present in 7.4% of patients with RP, which is lower than the prevalence reported earlier. Although vitrectomy can improve the macular morphology in some patients with RP, improvement of visual function may be limited most likely because of the long-standing retinal dysfunction.


Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis.

Purpose. To assess the effects of spermidine on the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), with a focus on optic neuritis often associated with MS and EAE. Methods. Myelin oligodendrocyte glycoprotein-induced EAE mice were administered with or without spermidine at 30 mM in drinking water for 25 days. Clinical signs of EAE were scored daily and visual functions were measured by multifocal electroretinograms. Histopathology analysis of the spinal cord and optic nerve were performed after mice were sacrificed on day 25. Hydrogen peroxide (H(2)O(2)) was detected using the probe 2'-7' dichlorofluorescein diacetate (DCFDA) in the optic nerve. The effect of spermidine on H(2)O(2)-induced retinal ganglion cell apoptosis was investigated by lactate dehydrogenase assay. Results. Everyday clinical scoring revealed that the severity of EAE was significantly attenuated in spermidine-treated group, which was confirmed by milder demyelination and improved axon survival in the spinal cord of spermidine-treated mice. Visual functions were significantly improved in spermidine-treated mice compared with vehicle-treated mice. Spermidine treatment ameliorated the extent of demyelination in the optic nerve and prevented cell loss in the retinal ganglion cell layer. Furthermore, fewer DCFDA-labeled cells were found in the optic nerve in the spermidine-treated EAE mice, and in vitro analysis revealed that spermidine reduced H(2)O(2)-induced retinal ganglion cell apoptosis, suggesting that spermidine alleviated the severities of EAE, particularly of optic neuritis, by acting as an antioxidant. Conclusions. The results from this study suggest that oral spermidine administration could be a useful treatment for MS.

Investigative Ophthalmology & Visual Science


Delayed onset of experimental autoimmune encephalomyelitis in Olig1 deficient mice.

Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS.

Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in Olig1(-/-) mice is significantly slower than wide-type (WT) mice (19.8 ± 2.2 in Olig1(-/-) mice and 9.5 ± 0.3 days in WT mice). In addition, 10% of Olig1(-/-) mice did not develop EAE by the end of the observation periods (60 days). The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1(-/-) mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1(-/-) mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1(-/-) mice.


Three cases of retinal arterial macroaneurysm on the optic disc

視神経乳頭上に生じた網膜細動脈瘤の3例

Retinal arterial macroaneurysm typically involves the second order arterioles and is relatively uncommon on the optic disc. Here, we present three cases of retinal arterial macroaneurysm. Case 1 was a 56-year-old woman, Case 2 was a 78-year-old man, and Case 3 was an 86-year-old man. In Cases 1 and 3, the fundus could not be observed visually at the time of initial examination because of vitreous bleeding. Retinal arterial macroaneurysm was revealed during vitrectomy. In Case 2, retinal arterial macroaneurysm was found on the optical disc along with a retinal hemorrhage which disappeared without any treatment. In all three cases, visual acuity was normal after treatment. Since retinal arterial macroaneurysm on the optical disc may be overlooked when treating vitreous bleeding in cases where the cause is not known, we believe that retinal arterial macroaneurysm should be taken into consideration as a possible underlying cause. While photocoagulation of retinal arterial macroaneurysm on the optic disc is infrequently used to, localized photocoagulation retinal arterial macroaneurysm on the optic disk is considered to be difficult. We are of the opinion that progression should be observed carefully till the macroaneurysm is absorbed.

Acta Societatis Ophthalmologicae Japonicae


Comparison of intravitreal bevacizumab to photodynamic therapy for polypoidal choroidal vasculopathy: short-term results.

AIMS: To compare the short-term therapeutic effects of intravitreal bevacizumab (IVB) to those of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). MATERIALS AND METHODS: Retrospective interventional case study. Eighty-nine eyes of 89 patients with symptomatic PCV were treated by IVB or PDT. Eighteen eyes were treated with a single injection of IVB (s-IVB group), 22 eyes with three consecutive monthly IVB injections (m-IVB group), and 49 eyes with PDT alone (PDT group). The best-corrected visual acuity (BCVA) and OCT-determined central foveal thickness (CFT) were evaluated before, and one and three months after the treatment. For statistical analyses, one-factor ANOVA and Chi-square test were used. RESULTS: The differences in the BCVA and CFT among the three groups at the baseline were not significant (P=0.992, P=0.981, respectively). Three months after the treatment, the BCVA improved by> 0.2 logMAR units in two out of 18 eyes (11%) in the s-IVB group, three out of 22 eyes (14%) in the m-IVB group, and 15 out of 49 eyes (31%) in the PDT group (P=0.124). A decrease in the CFT by> 20% was achieved in six out of 18 eyes in the s-IVB group, ten eyes (46%) in the m-IVB group, and 35 eyes (71%) in the PDT group (P=0.009). The resolution of polyps was achieved in three out of 18 eyes in the s-IVB group, one eye (5%) in the m-IVB group and 35 eyes (71%) in the PDT group (P < 0.001). CONCLUSION: The better short-term therapeutic outcomes in the PDT group than in the s-IVB and m-IVB groups indicate that PDT may be more effective than IVB in short term after treatment for PCV.


ASK1 deficiency attenuates neural cell death in GLAST-deficient mice, a model of normal tension glaucoma.

Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced retinal ganglion cell (RGC) apoptosis. In the mammalian retina, glutamate/aspartate transporter (GLAST) is a major glutamate transporter, and the loss of GLAST leads to optic nerve degeneration similar to normal tension glaucoma (NTG). In GLAST(-/-) mice, the glutathione level in the retina is decreased, suggesting the involvement of oxidative stress in NTG pathogenesis. To test this hypothesis, we examined the histology and visual function of GLAST(+/-):ASK1(-/-) and GLAST(-/-):ASK1(-/-) mice by multifocal electroretinograms. ASK1 deficiency protected RGCs and decreased the number of degenerating axons in the optic nerve. Consistent with this finding, visual function was significantly improved in GLAST(+/-):ASK1(-/-) and GLAST(-/-):ASK1(-/-) mice compared with GLAST(+/-) and GLAST(-/-) mice, respectively. The loss of ASK1 had no effects on the production of glutathione or malondialdehyde in the retina or on the intraocular pressure. Tumor necrosis factor (TNF)-induced activation of p38 MAPK and the production of inducible nitric oxide synthase were suppressed in ASK1-deficient Müller glial cells. In addition, TNF-induced cell death was suppressed in ASK1-deficient RGCs. These results suggest that ASK1 activation is involved in NTG-like pathology in both neural and glial cells and that interrupting ASK1-dependent pathways could be beneficial in the treatment of glaucoma, including NTG.Cell Death and Differentiation advance online publication, 21 May 2010; doi:10.1038/cdd.2010.62.


Changes of fundus autofluorescence, photoreceptor inner and outer segment junction line, and visual function in patients with retinitis pigmentosa.

Abstract Background: To determine whether a significant correlation exists among the changes in the size of the abnormal parafoveal autofluorescence ring, the length of the photoreceptor inner and outer segment (IS/OS) junction, and the visual function in patients with retinitis pigmentosa. Methods: Retrospective observational case series. A total of 50 eyes of 26 patients with typical retinitis pigmentosa and an autofluorescence ring were examined by optical coherence tomography and microperimetry. During the follow-up period of >2 years, the changes in the diameter and area of the autofluorescence ring, the length of the IS/OS line, the best-corrected visual acuity and mean retinal sensitivity in the central 10 degrees were determined. Results: The diameter and area of the autofluorescence ring, and the length of the IS/OS line decreased significantly during the follow-up period (all, P < 0.0001). The decrease in autofluorescence ring diameter was significantly correlated with the decrease in retinal sensitivity, visual acuity and IS/OS length (P = 0.0105, P = 0.0252 and P < 0.0001, respectively). The decrease in autofluorescence ring area was significantly correlated with the decrease in retinal sensitivity, visual acuity and IS/OS length (P < 0.0001, P = 0.0026 and P = 0.0011, respectively). Conclusion: During the progression of retinitis pigmentosa, the progressive constriction of the autofluorescence ring reflects the morphological changes of the photoreceptors, and is associated with a worsening of visual function.


Expression of Epiplakin1 in the developing and adult mouse retina.

PURPOSE: To assess the expression of Epiplakin1 (Eppk1) in the developing and adult mouse retina. METHODS: Eppk1 expression was examined using reverse transcription-polymerase chain reaction (RTPCR) analysis and immunoblot analysis. The Eppk1 expression pattern was examined by immunohistochemical analysis in embryonic and adult C57BL/6J mice. RESULTS: Both Eppk1 mRNA and protein were detected in adult mouse retina. Eppk1 was expressed in nestin-positive neural progenitor cells in the embryonic retina. In adults, Eppk1 was expressed in retinal ganglion cells, bipolar cells, and Müller glial cells. CONCLUSIONS: These results suggest that Eppk1 is expressed both in embryonic and adult retina and may be involved in retinal development.


Expression of NG2-positive cells during optic neuritis.


Transcription factor, SP1, in epiretinal membranes of patients with proliferative diabetic retinopathy.

SP1 mRNA was highly expressed in the epiretinal membranes of proliferative diabetic retinopathy (PDR), and the SP1 protein was mainly co-localized with vascular endothelial growth factor. SP1 might play an important role in the angiogenesis of PDR by regulating the promoter activity and expression of genes encoding angiogenesis-related factors.


Two-year comparison of photodynamic therapy and intravitreal bevacizumab for treatment of myopic choroidal neovascularisation.

AIM: To compare the long-term outcome of photodynamic therapy (PDT) with that of intravitreal bevacizumab (IVB) for myopic choroidal neovascularizations (mCNVs). METHODS: 24 eyes were selected from 40 consecutive patients with mCNV, and the patients were divided into Group A, consisting of 12 eyes treated by PDT, and Group B, consisting of 12 eyes treated by 1.25 mg IVB. The age and best-corrected visual acuity (BCVA) were matched between the two groups. The BCVA, size of the chorioretinal atrophy surrounding the CNV (CRA), central foveal thickness (CFT) and CNV thickness were determined before and at 12 and 24 months after the treatment. RESULTS: The BCVA did not change after PDT but was significantly improved from 0.75+/-0.25 to 0.49+/-0.42 logMAR units at 12 months and to 0.50+/-0.38 logMAR units at 24 months after IVB. The CFT were significantly reduced in both groups at 12 and 24 months. The CRAs were larger in group A than in group B at 12 and 24 months, and their sizes were correlated with the BCVA. CONCLUSION: At 24 months, IVB is more effective than PDT in treating mCNV. The enlargement of the CRA might be related to the incomplete visual recovery after PDT.


Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice.

Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of retinal ganglion cells (RGCs) and optic nerves. Although glaucoma is often associated with elevated intraocular pressure, recent studies have shown a relatively high prevalence of normal tension glaucoma (NTG) in glaucoma patient populations. In the mammalian retina, glutamate/aspartate transporter (GLAST) is localized to Müller glial cells, whereas excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Since the loss of GLAST or EAAC1 leads to retinal degeneration similar to that seen in NTG, we examined the effects of interleukin-1 (IL-1) on RGC death in GLAST- and EAAC1-deficient mice. IL-1 promoted increased glutamate uptake in Müller cells by suppressing intracellular Na(+) accumulation, which is necessary to counteract Na(+)-glutamate cotransport. The observed trends for the glutamate uptake increase in the wild-type (WT), GLAST- and EAAC1-deficient mice were similar; however, the baseline glutamate uptake and intracellular Na(+) concentration in the GLAST-deficient mice were significantly lower than those in the wild-type mice. Consistently, pretreatment with IL-1 exhibited no beneficial effects on glutamate-induced RGC degeneration in the GLAST-deficient mice. In contrast, IL-1 significantly increased glutamate uptake by Müller cells and the number of surviving RGCs in the wild-type and EAAC1-deficient mice. Our findings suggest that the use of IL-1 for enhancing the function of glutamate transporters may be useful for neuroprotection in retinal degenerative disorders including NTG.


Changes in visual function and thickness of macula after photodynamic therapy for age-related macular degeneration.

PURPOSE: To determine the correlation between the changes in the central retinal sensitivity and the changes in the foveal thickness (FT) after photodynamic therapy (PDT) for age-related macular degeneration (AMD). METHODS: Nineteen eyes of 19 patients with choroidal neovasularizations (CNVs) secondary to AMD were studied. The pretreatment values of the central retinal sensitivity determined by Micro Perimeter 1 (MP1; Nidek Technologies), best-corrected visual acuity (BCVA), and optical coherence tomography (OCT)-determined FT were compared to the postoperative values at three and six months after PDT. RESULTS: At six months, the retinal sensitivity within the central 10 degrees was significantly improved (P = 0.02) and the FT was significantly thinner (P = 0.016). The BCVA, however, did not change significantly (P = 0.80). The changes in the retinal sensitivities were significantly correlated with the changes in the decrease in the FT (r = - 0.59, P = 0.012 within the central 10 degrees ) at six months after PDT. CONCLUSION: Significant improvements in retinal sensitivities within the central 10 degrees and a decrease in FT were observed even though the BCVA was not significantly improved. The measurement of retinal sensitivity by MP1 may be a better method to assess central visual function than the conventional visual acuity after PDT.


Changes of multifocal electroretinogram after intravitreal bevacizumab for macular edema due to branch retinal vein occlusion

網膜静脈分枝閉塞症の黄斑浮腫に対する bevacizumab 硝子体内投与後の多局所網膜電図

Folia japonica de ophthalmologica clinica


Subthreshold Micropulse Diode Laser Photocoagulation for Diabetic Macular Edema with Hard Exudates

硬性白斑が集積する糖尿病黄斑浮腫に対するマイクロパルス・ダイオードレーザー閾値下凝固の治療成績

To examine the efficacy of subthreshold micropulse diode laser photocoagulation (SMDLP) in eyes with diabetic macular edema (DME) with hard exudates. Ten eyes of 10 patients with diffuse DME were treated with SMDLP (810 nm). Hard exudates had accumulated within the foveal avascular zone (FAZ) in all patients. The mean retinal sensitivity within the central 10 degrees was measured with a fundus-related microperimeter (MP 1); the best corrected visual acuity (BCVA) in logMAR units and optical coherence tomography (OCT)-determined foveal thickness (FT) were recorded before and at 3 months after SMDLP. The FT did not decrease significantly after SMDLP, but the BCVA improved significantly from 0.51 +/- 0.25 to 0.40 +/- 0.31 logMAR units (p= 0.02). There was no significant change in the mean retinal sensitivity within the central 10 degrees after SMDLP. SMDLP can improve the visual acuity even in eyes with DME and hard exudates. However, the therapeutic efficacy of SMDLP in these cases may be limited, because no significant improvement in either the foveal thickness or retinal sensitivity could be seen.

Acta Societatis Ophthalmologicae Japonicae


Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis.

Optic neuritis is an acute inflammatory demyelinating syndrome of the central nervous system (CNS) that often occurs in multiple sclerosis (MS). Since it can cause irreversible visual loss, especially in the optic-spinal form of MS or neuromyelitis optica (NMO), the present study was conducted to assess the effects of geranylgeranylacetone (GGA) on optic neuritis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Myelin oligodendrocyte glycoprotein-induced EAE mice received oral administration of GGA at 500 mg/kg or vehicle once daily for 22 days. The effects of GGA on the severity of optic neuritis were examined by morphological analysis on day 22. Visual functions were measured by the multifocal electroretinograms (mfERG). In addition, the effects of GGA on severity of myelitis were monitored both on clinical signs and morphological aspects. The visual function, as assessed by the second-kernel of mfERG, was significantly improved in GGA-treated mice compared with vehicle-treated mice. GGA treatment decreased the number of degenerating axons in the optic nerve and prevented cell loss in the retinal ganglion cell layer. However, the severity of demyelination in the spinal cord remained unaffected with the treatment of GGA. These results suggest that oral GGA administration has beneficial effect on the treatment for optic neuritis in the EAE mouse model of MS.


Efficacy of vitrectomy and internal limiting membrane removal for macular edema associated with branch retinal vein occlusion.

AIM: To compare the results of vitrectomy with internal limiting membrane (ILM) peeling to that without ILM peeling for macular edema associated with branch retinal vein occlusion (BRVO). METHODS: The medical records of 47 eyes of 47 patients with BRVO-associated macular edema were examined. To treat the macular edema, a posterior vitreous detachment (PVD) was created, and the ILM was removed in 13 eyes (ILM-removed group), whereas a PVD was created and the ILM was not removed in 34 eyes (ILM-preserved group). The best-corrected visual acuity (BCVA) and the optical-coherence-tomography-determined foveal thickness were obtained preoperatively and at 6 months postoperatively. RESULTS: The mean postoperative BCVA was significantly better than the preoperative BCVA in both the ILM-removed and in the ILM-preserved groups (p = 0.0017 and p = 0.0002, respectively). The fovea was significantly thinner at 1 month after surgery in both groups (p = 0.0007 and p < 0.0001, respectively). The postoperative improvement of the mean BCVA and the foveal thickness were not significantly different for the two groups at any postoperative period. CONCLUSIONS: Because there was no significant difference in the improvement of BCVA between the two groups at 6 months postoperatively, there may be no additional benefit in removing the ILM for BRVO-associated macular edema.


Vitrectomy alone versus vitrectomy with simultaneous intravitreal injection of triamcinolone for macular edema associated with branch retinal vein occlusion.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of vitrectomy with simultaneous intravitreal injection of triamcinolone acetonide for macular edema associated with branch retinal vein occlusion. PATIENTS AND METHODS: A retrospective study of 45 eyes with macular edema associated with branch retinal vein occlusion. A posterior vitreous detachment was created and the vitreous cortex was completely removed, after which 23 eyes immediately had an intravitreal injection of triamcinolone acetonide (triamcinolone acetonide group) and 22 eyes did not (no triamcinolone acetonide group). Visual acuity, fluorescein angiograms, and foveal thickness determined by optical coherence tomography were examined preoperatively and postoperatively. RESULTS: Mean postoperative visual acuity at 12 months was significantly better than the preoperative visual acuity in both groups. The fovea was significantly thinner 1 month postoperatively in both groups. Foveal thickness gradually decreased until 12 months in the no triamcinolone acetonide group; however, foveal thickness increased for 12 months in the triamcinolone acetonide group. A recurrence of macular edema was more frequent in the triamcinolone acetonide group than in the no triamcinolone acetonide group (P = .006). CONCLUSIONS: Because there was no significant difference in the improvement of best-corrected visual acuity between the groups 12 months postoperatively, there may be no benefit in the use of intraoperative intravitreal triamcinolone acetonide.


Surgical Outcome of Vitrectomy for Uveitis

ぶどう膜炎に対する硝子体手術成績


Increased expression of IRE1α and stress-related signal transduction proteins in ischemia-reperfusion injured retina.

The purpose of this study was to determine whether the expression of ER stress-related factors IRE1alpha, apoptosis signal-regulating kinase 1 (ASK1), SAPK/ERK kinase 1 (SEK1) and c-Jun N-terminal kinase (JNK) is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1alpha, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1alpha immunoreactivity in the ganglion cell layer (GCL) were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.


Correlation of visual recovery with presence of photoreceptor inner/outer segment junction in optical coherence images after epiretinal membrane surgery.

AIMS: To investigate the relationship between the presence of the photoreceptor inner and outer segment (IS/OS) junction and visual acuity after epiretinal membrane (ERM) surgery. METHODS: Seventy eyes of 70 consecutive patients who had undergone vitrectomy for idiopathic ERM were examined by optical coherence tomography before and 3 and 6 months after surgery. The IS/OS junction was graded into three grades. The time course of recovery of the IS/OS junction, central foveal thickness (CFT) and best corrected visual acuity (BCVA) during the postoperative period was studied. RESULTS: A normal IS/OS junction was detected in 47.1% of the eyes before surgery and in 65.7% at 3 months and 75.7% at 6 months after. There was a significant correlation between the IS/OS grade and BCVA before and at 3 and 6 months after the operation (p = 0.0001, p<0.0001, p<0.0001, respectively). The preoperative IS/OS junction grade correlated significantly with BCVA at 6 months (p = 0.0239). CFT did not correlate significantly with BCVA at 3 and 6 months. CONCLUSIONS: The presence of a normal IS/OS junction was associated with good visual acuity after ERM surgery. A normal IS/OS junction probably indicates morphological and functional recovery of the photoreceptors.


A case of retinal hemangioma treated by vitrectomy for vitreous hemorrhage and epimacular membrane

網膜血管腫に伴う硝子体出血と黄斑上膜に対して硝子体手術を行った1例 (特集 第61回日本臨床眼科学会講演集(6))

Japanese Journal of Clinical Ophthalmology


A case of serous retinal detachment following vitrectomy for rhegmatogenous retinal detachment

裂孔原性網膜剥離の硝子体手術後に漿液性網膜剥離を認めた1例

Folia japonica de ophthalmologica clinica


Correlation of visual recovery and presence of photoreceptor inner/outer segment junction in optical coherence images after successful macular hole repair.

PURPOSE: To determine the relationship between the postoperative visual acuity (VA) and the presence of a photoreceptor inner segment (IS) and outer segment (OS) junction (IS/OS) in optical coherence tomographic (OCT) images after macular hole (MH) surgery. METHODS: Twenty-three eyes of 23 cases of idiopathic MH treated by vitrectomy were studied. The postoperative VA and OCT3 images of the fovea at 1, 3, and 6 months were examined. The relationship between the presence of the IS/OS junction and the visual acuity was studied. RESULTS: All MHs were successfully closed. The IS/OS junction appeared as a distinct, highly reflective line just vitread to the retinal pigment epithelial layer in the postoperative OCT3 images. A normal IS/OS junction was detected postoperatively in one eye at 1 month, three eyes at 3 months, and seven eyes at 6 months. The VA was significantly better in eyes in which a normal IS/OS junction was detected than in those not detected at 3 and 6 months postoperatively (P = 0.046 and P = 0.040, respectively). CONCLUSION: The normal IS/OS junction observed in OCT3 images is associated with good visual recovery after MH closure. The presence of normal IS/OS junction may be important for visual recovery after MH repair.


Severe macular edema induced by pioglitazone in a patient with diabetic retinopathy: a case study.

We report a case of severe diabetic macular edema (DME) that developed after pioglitazone was used by a patient with proliferative diabetic retinopathy. A 30-year-old woman with poorly controlled type 2 diabetes mellitus visited our clinic in 2004. She had moderate pre-proliferative diabetic retinopathy OU. Because of the rapid progression of the diabetic retinopathy, she received pan-retinal photocoagulation in both eyes. Two weeks before using pioglitazone, her visual acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was prescribed by her internist because of poorly controlled blood glucose level. Two weeks later, her body weight increased, and her face became edematous. Her visual acuity decreased to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes. Two weeks after stopping pioglitazone, her visual acuity improved to 0.8 OD and 0.5 OS, but the DME was still severe in the optical coherence tomographic images. Then, one half the usual dose (25 mg) of spironolactone, a diuretic, was given and her macular edema was resolved. Her final visual acuity improved to 0.9 OD and 0.7 OS. We recommend that when a patient taking pioglitazone complains of decreased vision, the physician should promptly consult an ophthalmologist.


Neuroprotective effect of geranylgeranylacetone against ischemia-induced retinal injury.

PURPOSE: This study was conducted to assess the effects of geranylgeranylacetone (GGA) on ischemia-induced retinal injury. METHODS: Adult C57BL/6J mice were given oral treatments of GGA at 200 mg/kg daily for seven days. Ischemic retinal injury was carried out, and the extent of retinal cell death was quantitatively examined after 7 days. Immunohistochemistry for single-stranded DNA, phosphorylated form of p38 mitogen-activated protein kinase (p38 MAPK), and cleaved caspase-3 were performed one day after ischemic injury. RESULTS: In GGA-treated mice, we found the number of surviving retinal neurons was significantly increased compared with vehicle-treated mice. Ischemia-induced phosphorylation of p38 MAPK, which mediates apoptosis of retinal ganglion cells, was suppressed by GGA treatment. In such retinas, cleaved caspase-3- and single-stranded DNA-positive cells were also decreased compared with vehicle-treated mice. CONCLUSIONS: Oral GGA is a useful treatment for various retinal degenerative diseases that involve ischemic injury.


Glial cell-derived cytokines attenuate the breakdown of vascular integrity in diabetic retinopathy.

The blood-retinal barrier (BRB) is a biological unit comprised of specialized capillary endothelial cells firmly connected by intercellular tight junctions and endothelium-surrounding glial cells. The BRB is essential for maintaining the retinal microenvironment and low permeability and is compromised in an early phase during the progression of diabetic retinopathy. Here, we demonstrate that retinoic acid receptor (RAR)alpha stimulants preferentially act on glial cells rather than endothelial cells, resulting in the enhanced expression of glial cell line-derived neurotrophic factor (GDNF) through recruitment of the RARalpha-driven trans-acting coactivator to the 5'-flanking region of the gene promoter. Conversely, RARalpha decreases expression of vascular endothelial growth factor (VEGF)/vascular permeability factor. These gene expression alterations causally limit vascular permeability by modulating the tight junction function of capillary endothelium in a paracrine manner in vitro. The phenotypic transformation of glial cells mediated by RARalpha is sufficient for significant reductions of vascular leakage in the diabetic retina, suggesting that RARalpha antagonizes the loss of tight junction integrity induced by diabetes. These findings reveal that glial cell-derived cytokines such as GDNF and VEGF regulate BRB function, implying that the glial cell can be a possible therapeutic target in diabetic retinopathy.


A Case of Branch Retinal Artery Occlusion Associated with Rupture of Retinal Arterial Macroaneurysm

網膜細動脈瘤破裂後に自然経過で網膜動脈分枝閉塞症を合併した1例


Changes in multifocal oscillatory potentials after internal limiting membrane removal for macular hole: multifocal OPs after ILM removal.

PURPOSE: To determine whether removal of the internal limiting membrane (ILM) during macular hole (MH) surgery alters the retinal function. METHODS: Multifocal electroretinograms (mfERGs) were recorded preoperatively and 3 months after surgery from 11 eyes of 10 patients with an idiopathic MH treated successfully by pars plana vitrectomy accompanied by ILM removal. A low frequency (9.4 Hz) pseudorandom binary m-sequence stimulus was used to elicit the mfERGs from different retinal loci. The bandpass of the amplifier was set at 10-300 Hz to record the mfERGs and at 100-300 Hz to record the oscillatory potentials (OPs). RESULTS: An anatomical closure of the MH was achieved in all patients, and the mean visual acuity was significantly improved postoperatively. No significant difference was observed in both the amplitudes and implicit times of the negative and positive waves of the mfERGs and the OPs recorded preoperatively to those recorded postoperatively. CONCLUSIONS: MH surgery with ILM removal does not alter the electrophysiological function of both the outer and inner retina of the posterior pole where the ILM was removed.


A Case of Central Retinal Artery Occlusion and Anterior Ischemic Optic Neuropathy Associated with Temporal Arteritis

側頭動脈炎に網膜中心動脈閉塞症と前部虚血性視神経症を合併した1例


Young Female with Cilioretinal Artery Occlusion and Impending Central Retinal Vein Occlusion

毛様網膜動脈閉塞症と切迫網膜中心静脈閉塞症を併発した若年女性の1例


Optical Coherence Tomographic Findings of Spontaneous Closure of Traumatic Macular Hole

自然閉鎖した外傷性黄斑円孔のOCT所見


Role of monocyte chemotactic protein-1 and nuclear factor kappa B in the pathogenesis of proliferative diabetic retinopathy.

Intraocular concentrations of monocyte chemotactic protein-1 (MCP-1) are increased in proliferative diabetic retinopathy (PDR). Nuclear factor kappa B (NF-kappaB) is a transcription factor, and NF-kappaB binding site is located in gene promoter of MCP-1. This study was conducted to investigate the potential role of MCP-1 and NF-kappaB in the pathogenesis of PDR. Epiretinal membrane (ERM) samples were obtained during vitrectomy from 19 eyes with PDR and 16 eyes with idiopathic ERM. They were processed for RT-PCR analysis. Four PDR ERMs were processed for immunohistochemical analysis. In addition, cultured Müller glial cells were stimulated with glycated albumin or high glucose. After the stimulation, we examined nuclear localization of NF-kappaB p50, MCP-1 promoter activity, and MCP-1 concentration in culture media. MCP-1 mRNA expression was significantly higher in PDR (74%) than in idiopathic ERMs (38%) (P < 0.05). Immunohistochemical analysis revealed that MCP-1 protein is colocalized with active form of NF-kappaB p50. In vitro studies demonstrated that glycated albumin or high glucose induces NF-kappaB activation followed by up-regulation of MCP-1 promoter activity and protein production in glial cells. These results suggest that MCP-1, under the regulation of NF-kappaB, is involved in the pathogenesis of PDR.


Surgical Outcome of Vitrectomy for Retinal Detachment Due to Macular Hole in Highly Myopic Eyes

高度近視に伴う黄斑円孔網膜剥離の硝子体手術成績


Vitrectomy for Diabetic Macular Edema Associated with Vitreomacular Traction

硝子体黄斑牽引を伴う糖尿病黄斑浮腫に対する硝子体手術


Natural Course of Highly Myopic Eyes with Foveal Detachment, Retinoschisis, and No Macular Hole

強度近視眼における黄斑剥離, 網膜分離の黄斑円孔発症前の自然経過


Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo.

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in oxidative stress-induced apoptosis. In the present study, we used ASK1 knockout (KO) mice to examine the possibility that ASK1 is involved in the neural cell apoptosis that occurs during retinal development and ischemic injury. ASK1 was expressed in retinal neurons, including retinal ganglion cells (RGCs), but retinal structure and extent of cell death during development were normal in ASK1 KO mice. On the other hand, the strain was less susceptible to ischemic injury, and the number of surviving retinal neurons was significantly increased compared with that in wild-type mice. Interestingly, ischemia-induced phosphorylation of p38 mitogen-activated protein kinase (p38), which mediates RGC apoptosis, was almost completely suppressed in ASK1 KO mice. In such retinas, the numbers of cleaved caspase-3- and TUNEL-positive neurons were apparently decreased compared with those in wild-type mice. Furthermore, cultured RGCs from ASK1 KO mice were resistant to H(2)O(2)-induced apoptosis. Our findings suggest that ASK1 is involved in the neural cell apoptosis after various kinds of oxidative stress. Thus, inhibition of the ASK1-p38 pathway could be useful for the treatment of neurodegenerative diseases including glaucoma.


Optical Coherence Tomographic Findings in Spontaneous Closure of Idiopathic Macular Hole

自然閉鎖した黄斑円孔症例のOCT所見


Effect of p75NTR on the regulation of photoreceptor apoptosis in the rd mouse.

PURPOSE: Apoptosis is the final common pathway for photoreceptors in several forms of retinitis pigmentosa. Recent study has shown that continuous light exposure upregulates low-affinity neurotrophin receptor p75 (p75NTR), which is involved in light-induced photoreceptor apoptosis in rat retina. However, the function of p75NTR in inherited forms of photoreceptor degeneration has not yet been examined. This study was conducted to elucidate the potential role of p75NTR in the rd mouse, one of the best characterized animal models of retinitis pigmentosa. METHODS: Double-mutant (rd/rd, p75NTR-/-) mice were crossbred from rd/rd and p75NTR-/- mice. Retinas from control (+/+, p75NTR+/+; rd/rd, p75NTR+/+; rd/rd, p75NTR+/-), and double-mutant (rd/rd, p75NTR-/-) mice were examined by light microscopy and TdT-mediated dUTP nick end labeling (TUNEL) from postnatal day (P)9 through P20. p75NTR mRNA expression in +/+, p75NTR+/+, and rd/rd, p75NTR+/+ mice were examined by real-time PCR analysis. p75NTR protein expression in +/+, p75NTR+/+; rd/rd, p75NTR+/+; and rd/rd, p75NTR-/- mice were examined by immunohistochemistry. RESULTS: p75NTR mRNA expression in rd/rd, p75NTR+/+ mice was significantly upregulated compared with +/+, p75NTR+/+ mice at P13 and P20. p75NTR protein expression was observed mainly in Müller glial cells, and its expression was upregulated in the outer nuclear layer during photoreceptor degeneration. However, histochemical analyses showed that the time course of retinal degeneration and the extent of photoreceptor apoptosis in rd/rd, p75NTR-/- double-mutant mice was indistinguishable from that in rd mice carrying functional p75NTR (rd/rd, p75NTR+/+, and rd/rd, p75NTR+/-). CONCLUSIONS: These results suggest that in contrast to its role in light-induced photoreceptor degeneration, p75NTR is not essential for apoptosis in the rd mouse.


Relationship of dissociated optic nerve fiber layer appearance to internal limiting membrane peeling.

PURPOSE: The dissociated optic nerve fiber layer (DONFL) appearance features numerous arcuate striae after vitrectomy for idiopathic epiretinal membrane or macular hole. We studied the relation between the DONFL appearance and internal limiting membrane (ILM) peeling and performed static microperimetry to explore the possible mechanisms underlying the DONFL appearance. DESIGN: Prospective cohort study. PARTICIPANTS: Ninety-five eyes of 88 consecutive patients undergoing vitrectomy for idiopathic macular hole. METHODS: Vitrectomy and gas tamponade were performed with or without ILM peeling. All eyes were examined postoperatively using fundus photography with blue filters. Static microperimetry was performed in 31 eyes with a clearly visible DONFL appearance. MAIN OUTCOME MEASURE: The postoperative incidence of the DONFL appearance on blue-filtered fundus photographs. The secondary outcome measure included the microperimetry threshold value in the arcuate striae and the surrounding normal retina within the papillomacular bundle. RESULTS: On blue-filtered photographs, 46 (62.2%) of 74 eyes with ILM peeling exhibited the DONFL appearance, compared with 0 (0%) of 21 eyes without ILM peeling (P = 0.0002). The area of the DONFL appearance was limited to the area of ILM peeling. There was no difference in the microperimetry threshold value between the arcuate striae and the surrounding normal retina (P = 0.9312). CONCLUSION: The present study indicates that the DONFL appearance might be related to ILM peeling and is not associated with the loss of optic nerve fibers. These results are consistent with the suggestion that the DONFL appearance might be caused by cleavage of the optic nerve fiber bundles due to damage to the Müller cells, which are in close contact with the ILM and act to maintain the close proximity of the nerve fiber bundles.


悪性奇形腫型髄様上皮腫の1例

悪性奇形腫型髄様上皮腫の1例


Retinal Arteriolar Macroaneurysm on the Optic Disc

視神経乳頭上に生じた網膜細動脈瘤


A Case of Retinitis Pigmentosa with Tractional Retinal Detachment

網膜色素変性症に合併した牽引性網膜剥離の1例


A Case of Chronic Myeloid Leukemia and Hyperviscosity Syndrome with Peripheral Retinal Nonperfusion and Vitreous Hemorrhage

過粘稠度症候群により周辺部網膜虚血, 硝子体出血をきたした慢性骨髄性白血病の1例


Optical coherence tomographic findings of dissociated optic nerve fiber layer appearance.

PURPOSE: To examine the features of optical coherence tomographic (OCT) findings of dissociated optic nerve fiber layer (DONFL) appearance. DESIGN: Case-control study. METHODS: Twenty-four eyes undergoing vitrectomy for idiopathic epiretinal membrane or macular hole were examined postoperatively using OCT. RESULTS: Thirteen of the 24 eyes exhibited the DONFL appearance. In these 13 eyes, the OCT images indicated dimples in the retinal nerve fiber layer (RNFL) corresponding to each stria. The RNFL thickness (mean +/- SD) at the dimple site was 38.1 +/- 9.3 microm. The depth of each dimple was 28.6 +/- 8.0 microm. The depths of all the dimples were limited to the RNFL thickness. In the other 11 eyes without the DONFL appearance, OCT images showed no distinct dimples. CONCLUSIONS: The DONFL appearance is caused by dimples the depths of which are limited to the RNFL thickness.


Two Cases with Adenoma of Ciliary Body Nonpigmented Epithelium

無色素上皮由来の毛様体腺腫の2症例


Three Cases of High Myopia with Foveal Detachment, Retinoschisis and No Macular Hole

強度近視眼における黄斑円孔を伴わない黄斑剥離, 網膜分離の3症例


Dissociated Optic Nerve Fiber Layer Appearance after Vitrectomy for Idiopathic Epiretinal Membrane or Macular Hole

黄斑上膜, 黄斑円孔手術後の Dissociated Optic Nerve Fiber Layer Appearance


A Case of Endophthalmitis 8 Years after Transscleral Fixation of Intraocular Lens

眼内レンズ毛様溝縫着術8年後に発症した眼内炎の1例


Nodular scleritis and panuveitis with erythema elevatum diutinum.

PURPOSE: To report a case of nodular scleritis and panuveitis associated with erythema elevatum diutinum, a rare immunocomplex-mediated skin disease. DESIGN: Observational case report. METHODS: A 22-year-old woman who was diagnosed with erythema elevatum diutinum developed nodular scleritis and panuveitis of the right eye. She had experienced peripheral ulcerative keratitis with corneal perforation. RESULTS: All other known causes of nodular scleritis and panuveitis were investigated and ruled out. CONCLUSIONS: Erythema elevatum diutinum should be considered as an underlying systemic disease associated with nodular scleritis and panuveitis as well as peripheral keratitis.


Diverse NF-kappaB expression in epiretinal membranes after human diabetic retinopathy and proliferative vitreoretinopathy.

PURPOSE: Formation of epiretinal membranes (ERMs) after proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) results in progressive deterioration of vision, but its pathogenic mechanisms are still unknown. This study was conducted to examine the role of nuclear factor kappa B (NF-kappaB) in the formation of ERMs after PDR and PVR. METHODS: ERM samples were obtained by vitrectomy from 10 patients with PDR (aged 53+/-12 years with 14+/-5 years of diabetes), 20 patients with PVR, and 17 patients with idiopathic ERMs. Ten PVR and 17 idiopathic ERM samples were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 10 PDR and 10 PVR membranes were processed for immunohistochemical analysis. RESULTS: NF-kappaB mRNA expression levels were significantly higher (10 of 10 versus 9 of 17 subjects in idiopathic ERM, p=0.0119) in PVR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in 8 of the 10 PDR samples as well as all 10 PVR samples, and NF-kappaB positive cells were partially double labeled with glial cell markers. Interestingly, NF-kappaB protein was also overlapped with angiogenic factor interleukin-8 (IL-8) in glial cells as well as vascular endothelial cells. CONCLUSIONS: These results suggest that NF-kappaB is involved in the formation of both glial and vascular endothelial cell components, and that these two cell types might have functional interactions that lead to the enlargement of intraocular proliferative membranes.


Tenascin-C levels in the vitreous of patients with proliferative vitreoretinopathy.

PURPOSE: To determine whether tenascin-C levels are elevated in the vitreous of patients with proliferative vitreoretinopathy (PVR). METHODS: We assayed tenascin-C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes), rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of tenascin-C (median [range]) were significantly greater in PVR (845.0 ng/ml [411.0-1,050.0]) than in RRD (21.9 ng/ml [13.2-127.0]) and in the controls (18.0 ng/ml [9.9-199.0]) (p < 0.0001). CONCLUSION: The results indicate the possibility that tenascin-C is involved in the pathogenesis of PVR.


Rhegmatogenous retinal detachment after rupture of retinal arterial macroaneurysm.

PURPOSE: To report two cases of rhegmatogenous retinal detachment following rupture of retinal arterial macroaneurysm. DESIGN: Observational case report. METHODS: Review of clinical records of 75 consecutive eyes (73 patients) with macroaneurysm. RESULTS: Ruptured macroaneurysm was present in 68 of the 75 eyes, and rhegmatogenous retinal detachment developed spontaneously in 2 (2.9%) of the 68 eyes. In the 2 eyes with retinal detachment, there were no predisposing lesions to retinal detachment and the detachment occurred either 2 weeks or 1 month after the rupture of a macroaneurysm. Retinal detachment and posterior vitreous detachment developed simultaneously after bleeding from the macroaneurysm spread into the vitreous in 1 eye. CONCLUSIONS: We report the occurrence of retinal detachment after macroaneurysmal rupture. Detailed fun-dus examination is required to detect retinal detachment in the follow-up of patients with ruptured macroaneurysm.


Epidemic Nosocomial Keratoconjunctivitis Caused by Adenovirus Type 4

アデノウイルス4型結膜炎の院内感染

To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.

Acta Societatis Ophthalmologicae Japonicae


NF-kappaB in epiretinal membranes after human diabetic retinopathy.

AIMS/HYPOTHESIS: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to examine whether or not nuclear factor kappa B (NF-kappaB), a transcription factor that can be activated by various pathological conditions, is involved in the formation of ERMs after PDR. METHODS: ERM samples were obtained by vitrectomy from 22 cases with PDR aged 56+/-11 years with 18+/-10 years of diabetes and 15 cases with idiopathic ERM. They were processed for reverse transcription-polymerase chain reaction (RT-PCR) analysis. In addition, 5 ERM samples from PDR patients aged 51+/-16 years with 15+/-6 years of diabetes were processed for immunohistochemical analysis. RESULTS: NF-kappaB mRNA expression levels were higher (20 out of 22 cases vs. 9 out of 15 subjects in idiopathic ERM, p<0.05) in PDR subjects. Immunohistochemical analysis showed NF-kappaB protein expression in all the 5 ERMs derived from PDR patients, and that region was partially double-labelled with interleukin-8 (IL-8) and von Willebrand factor (vWF). CONCLUSIONS/INTERPRETATION: These results suggest a possibility that NF-kappaB is involved in the formation of ERMs after PDR, especially for the development of vascular endothelial cell component.


Macular hole formation following ruptured retinal arterial macroaneurysm.

PURPOSE: To report four cases of macular hole formation following ruptured retinal arterial macroaneurysm. DESIGN: Case-control study. METHODS: Review of clinical records of 75 consecutive eyes (73 patients) with macroaneurysm. Macroaneurysms were confirmed using either fluorescein angiography or indocyanine green angiography or both that indicated a telangiectatic retinal vascular change. Clinical data of patients with macroaneurysm with and without macular hole (MH) formation were compared retrospectively. RESULTS: Of 75 eyes, four (5.3%; four patients) with macroaneurysm had a macular hole. In one of the four eyes, a macular hole was detected 2 days after the rupture. The distance from the macroaneurysm to the center of the fovea was significantly closer in the four eyes with a macular hole (MH group, 1.1 +/- 0.4 (mean +/- standard deviation [SD]) disk diameter) than in the 71 eyes without a macular hole (non-MH group, 1.9 +/- 0.9 disk diameter) (P =.0196). The incidence of subretinal hemorrhage in the macula was significantly greater in the MH group (100%) than in the non-MH group (35.2%) (P =.0195). CONCLUSIONS: Macular hole formation associated with ruptured macroaneurysm is not as uncommon as previously thought. We suggest that there might be early onset of macular hole formation following ruptured macroaneurysm. Macroaneurysms with early-onset macular hole are present near the center of the macula and are accompanied by subretinal hemorrhage in the macula.


Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy.

OBJECTIVE: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75(NTR)]; glial cell line-derived neurotrophic factor receptor-alpha1 [GFR alpha 1] and GFR alpha 2; and Ret) are involved in the formation of ERMs after PDR. RESEARCH DESIGN AND METHODS: ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 +/- 8 years with 17 +/- 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 +/- 18 years with 13 +/- 4 years of diabetes were processed for immunohistochemical analysis. RESULTS: Expressions of trkA, trkB, trkC, p75(NTR), and Ret mRNAs were similar in both groups. In contrast, GFR alpha 2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFR alpha 2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFR alpha 1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects. CONCLUSIONS: These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.