Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

Corticobasal degeneration with deep white matter lesion diagnosed by brain biopsy.

Corticobasal degeneration (CBD) is a rare progressive neurodegenerative disorder characterized by asymmetric presentation of cerebral cortex signs, cortical sensory disturbance and extrapyramidal signs. Herein, we report a case of a 66-year-old Japanese woman who presented with apraxia of the right hand. She subsequently developed postural instability and cognitive impairments that rapidly worsened. One and a half years later, the patient was wheelchair-bound and severely demented. Brain magnetic resonance imaging revealed left dominant atrophy of the frontoparietal lobe. There was a hyperintense lesion in the deep white matter expanding toward the subcortical area on fluid-attenuated inversion recovery (FLAIR) images. In order to rule out the possibility of an intracranial tumor such as an astrocytoma or malignant lymphoma, we performed a brain biopsy of the left frontal middle gyrus. The patient became bedridden and showed akinetic mutism 1 year after biopsy. Pathological examination revealed a large amount of 4-repeat tau-immunoreactive neuropil threads scattered predominantly in the corticomedullary junction and tau-immunoreactive structures, consistent with CBD. Immunostaining for p53 showed no positive cells, and there were very few Ki-67-positive cells. On immunoblots of sarkosyl-insoluble brain extracts, a major doublet of 64 and 68 kDa full-length tau with two closely related fragments of approximately 37 kDa were detected. Based on these results, the patient was pathologically diagnosed as having CBD, excluding the possibility of tumor. Taken together with previous similar case reports, our findings indicate that a deep white matter hyperintense lesion on FLAIR images may be a useful clue to CBD, predicting rapid clinical progression with severe dementia based on severe white matter degeneration with a large amount of tau accumulation on pathological examination.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß2-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß2-microglobulin level higher than 10,000 µg/g cr. and a blood cadmium level higher than 6 µg/L or urinary cadmium level higher than 10 µg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).

Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

AFLIBERCEPT FOR POLYPOIDAL CHOROIDAL VASCULOPATHY: As Needed Versus Fixed Interval Dosing.

PURPOSE: To evaluate the functional and morphologic outcomes of patients with polypoidal choroidal vasculopathy undergoing intravitreal aflibercept (IVA) treatment using every 2-month injections compared with a pro re nata (PRN) regimen after 3 initial monthly doses. METHODS: The authors prospectively studied all the treatment-naive patients with polypoidal choroidal vasculopathy who were scheduled to undergo IVA using every 2-month injections or PRN after induction treatment between March 2013 and October 2013. All patients who had a follow-up period of 1 year or longer were included in the study. The best-corrected visual acuity in the 2 groups was compared before treatment and at 4 months, 6 months, and 12 months after the initial treatment. The regression of the polyps was also assessed using indocyanine-green angiography at baseline and 12 months. RESULTS: Forty-two eyes were assessed at the 12-month follow-up examination. Twenty-five eyes were treated with IVA injections every 2-month after 3 initial monthly doses, and 17 eyes were treated using PRN after loading doses. The mean number of administered IVA was 7.0 in the every 2-month group and 5.0 ± 2.9 in the PRN group, with significant difference between the 2 groups (P < 0.01). Both groups showed significant improvement of the mean logarithm of the minimum angle of resolution values for best-corrected visual acuity at 12 months, as compared with baseline values (P < 0.01 in every 8-week group and P = 0.03 in PRN group, respectively). No significant difference in the improvement of best-corrected visual acuity between the 2 groups was observed at baseline or at 4 months, 6 months, and 12 months after treatment (P > 0.05, respectively) although there was a trend toward better results in the every 8-week group. The rate of polyp regression was 48.0% (12/25) in the every 8-week group and 52.9% (9/17) in the PRN group, with no significant difference between the 2 groups (P = 0.50). CONCLUSION: Among the 2 treatment modalities, IVA was well tolerated and improved the visual outcomes in patients with polypoidal choroidal vasculopathy as evaluated at 1-year follow-up examinations. However, there was a trend toward better vision improvement with fixed treatment every 2 months.

Displacement of submacular hemorrhages in age-related macular degeneration with subretinal tissue plasminogen activator and air.

OBJECTIVE: To study the anatomic and visual outcomes of a surgical procedure in which tissue plasminogen activator and air are injected subretinally to displace massive submacular hemorrhages secondary to age-related macular degeneration. DESIGN: Prospective, consecutive, interventional case series. PARTICIPANTS: Thirteen consecutive patients (13 eyes) with massive submacular hemorrhages secondary to age-related macular degeneration. INTERVENTION: The surgical procedure consisted of a 25-gauge vitrectomy and submacular injection of tissue plasminogen activator (25 µg) and 0.4 ml air with a microneedle having an outer diameter of 50 µm. The procedure was followed by having the patient remain in the prone position overnight. MAIN OUTCOME MEASURES: Mean visual acuity change from baseline, mean central lesion thickness change from baseline, fluorescein angiography findings, and surgical complications. RESULTS: Total subfoveal blood displacement was achieved in all 13 eyes (100%). Central lesion thickness decreased from a mean baseline value of 867 µm to a mean value of 379 µm at 1 month after surgery. There was visual improvement in 11 eyes, no visual improvement in 1 eye, and poorer vision in 1 eye. The mean change in Early Treatment Diabetic Retinopathy Study letter score from baseline was 19.4 letters at 1 month (P = 0.006) and 23.3 letters at 3 months (P = 0.001). There was intraoperative macular hole formation. CONCLUSIONS: Submacular air injection with a microneedle facilitates displacement of clots dissolved with tissue plasminogen activator with few complications and results in earlier visual improvement.

Sutureless 27-gauge needle-guided intrascleral intraocular lens implantation with lamellar scleral dissection.

PURPOSE: To report a new technique for performing sutureless intrascleral fixation of a posterior chamber intraocular lens (IOL). DESIGN: Prospective, noncomparative, interventional case series on the results of sutureless intrascleral fixation of a posterior chamber IOL. PARTICIPANTS: Thirty-five eyes of 34 consecutive patients with aphakia, dislocated IOL, or subluxated crystalline lens who underwent posterior chamber sutureless implantation of an IOL were studied. METHODS: The haptics of the IOL were externalized with a 27-gauge needle passed through the ciliary sulcus using the double needle technique. The haptics were fixed in a scleral tunnel made by lamellar scleral dissection. The postoperative tilt of the IOL was measured by swept source optical coherence tomography. MAIN OUTCOME MEASURES: The best-corrected visual acuity (BCVA), corneal endothelial cell density, IOL tilt, and complications were determined. RESULTS: The IOLs were fixed with exact centration and axial stability. No wound leakage was seen even without any sutures. The mean BCVA was 0.48 logarithm of the minimum angle of resolution (logMAR) units preoperatively and 0.17 logMAR units at 3 months postoperatively (P = 0.003). The mean corneal endothelial cell loss was 6.0±7.3% (P = 0.63) at 3 months. The mean IOL tilt was 2.3±1.9°. The postoperative complications included iris capture by the IOL in 3 eyes (8.6%), ocular hypertension in 2 (5.7%), and cystoid macular edema in 1 (2.9%). There was no postoperative retinal detachment, endophthalmitis, IOL dislocation, or vitreous hemorrhage. CONCLUSIONS: The 27-gauge needle-guided intrascleral posterior chamber IOL implantation technique provides good IOL fixation with reliable wound closure without the use of any sutures. We recommend this technique for secondary IOL implantation.

Short-term efficacy of intravitreal aflibercept in treatment-naive patients with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the functional and morphologic outcomes of patients with polypoidal choroidal vasculopathy who underwent intravitreal aflibercept treatment. METHODS: We prospectively studied all the treatment-naive patients with polypoidal choroidal vasculopathy who were scheduled to undergo intravitreal aflibercept between February 2013 and July 2013. The best-corrected visual acuity was compared before treatment and at 6 months after the initial treatment. Changes in the central foveal thickness, choroidal thickness, presence/absence of subretinal fluid, fibrin, pigment epithelial detachment, and subretinal hemorrhage were also evaluated. The regression of the polyps was assessed using indocyanine green angiography. RESULTS: A total of 16 patients were included in this study. A significantly better best-corrected visual acuity at 6 months was seen, compared with that at baseline (P = 0.041). The mean central foveal thickness significantly decreased from 417 ± 127 µm to 187 ± 50 µm (P < 0.001). The mean choroidal thickness also significantly decreased from 250 ± 63 µm to 217 ± 64 µm (P = 0.011). Overall, a complete resolution was obtained in 93.3% (14/15) of the cases with subretinal fluid, 75.0% (3/4) of the cases with fibrin, and 88.9% (8/9) of the cases with subretinal hemorrhage. Fifty-six percent (5/9) of the cases with pigment epithelial detachment obtained a complete improvement, whereas 33.3% (3/9) exhibited a partial decrease. The rate of polyp regression was 75.0% (12/16). CONCLUSION: Intravitreal aflibercept was well tolerated and had improved the vision of treatment-naive patients with polypoidal choroidal vasculopathy when it was evaluated at short-term follow-up examinations. Intravitreal aflibercept might be associated with a high possibility of achieving involution of polyps and reducing exudative findings.

Neuropathological changes associated with aberrant cerebrospinal fluid p-tau181 and Aß42 in Alzheimer's disease and other neurodegenerative diseases.

Recent studies suggest that increased cerebrospinal fluid (CSF) phospho-tau is associated with brain amyloid pathology rather than the tau pathology. However, confirmation using gold standard neuropathological assessments remains limited. This study aimed to determine background pathologies associated with aberrant CSF p-tau181 and amyloid-beta 1-42 (Aß42) in Alzheimer's disease (AD) and other neurodegenerative diseases. We retrospectively studied all patients with antemortem CSF and postmortem neuropathologic data at our institution. Comprehensive neuropathologic assessments were conducted for all patients, including Thal phase, Braak NFT stage, and CERAD score for AD. CSF concentrations of p-tau181 and Aß42 were compared between AD neuropathological scores at autopsy by one-way ANOVA stratified by other pathologies. A total of 127 patients with AD (n = 22), Lewy body disease (n = 26), primary tauopathies (n = 30), TDP-43 proteinopathy (n = 16), and other diseases (n = 33) were included. The age at lumbar puncture was 76.3 ± 9.1 years, 40.8% were female, and median time from lumbar puncture to autopsy was 637 (175-1625) days. While Braak NFT 0-II was prevalent without amyloid pathology, Braak NFT ≥IV was observed exclusively in patients with amyloid pathology. Stratified analyses showed that CSF p-tau181 was slightly but significantly higher in patients with high Thal phase or CERAD score even in those with Braak NFT 0-II at autopsy. In patients with amyloid pathology, CSF p-tau181 was significantly and more profoundly elevated in those with Braak NFT ≥III at autopsy. CSF Aß42 was lower in patients with high amyloid pathological scores. However, 34% with Thal ≤ 2 and 38% with CERAD ≤ sparse also showed decreased Aß42. Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) were overrepresented in this group. These results neuropathologically confirmed previous studies that CSF p-tau181 levels were slightly elevated with amyloid pathology alone and were even higher with tau pathology, and that CSFAß42 can be decreased in PSP/CBD.

Variable response of vascularized pigment epithelial detachments to ranibizumab based on lesion subtypes, including polypoidal choroidal vasculopathy.

PURPOSE: The purpose of this study was to evaluate the prognosis and response to intravitreal ranibizumab (IVR) of neovascular age-related macular degeneration, according to the type of pigment epithelial detachment (PED). METHODS: The authors prospectively studied 57 eyes of 57 consecutive patients with PED associated with exudative age-related macular degeneration, who were treated by IVR. All patients received 3 consecutive monthly injections of 0.5 mg/0.05 mL of ranibizumab as induction treatment. Retreatment was allowed if evidence of clinical deterioration was noted or spectral domain optical coherence tomography at the 1-month follow-up showed intraretinal edema, subretinal fluid, or recurrent PED. The best-corrected visual acuity (BCVA) values measured before and at 3, 6, and 12 months after the first injection were compared according to the type of PED. Changes in the height of PED to treatment with IVR were also investigated. RESULTS: Fifty-six eyes were assessed at the 12-month follow-up examination. There were 4 types of PED, including serous PED in 11 patients (19.6%), fibrovascular PED in 28 patients (50.0%), mixed PED with serous and fibrovascular component in 7 patients (12.5%), and hemorrhagic PED in 10 patients (17.9%). Eyes with serous PED showed significant improvement of the mean logarithm of the minimum angle of resolution (logMAR) BCVA as compared with the value at the baseline, which was sustained throughout the 12-month period (P < 0.05). Regarding the eyes with fibrovascular and mixed PED, significant improvement of the mean logMAR BCVA was observed compared with the value at the baseline at 3 months; however, a slight decrease was observed at 6 and 12 months. In the eyes with hemorrhagic PED, no significant difference in the mean BCVA values compared with the value at the baseline was observed at any follow-up time point. In relation to the height of the PED, all eyes in the serous and mixed PED group, 17 eyes in the fibrovascular PED group (60.7%), and 9 eyes in the hemorrhagic PED group (90.0%) showed reduction of the maximum PED height by 100 µm or more. The PED response to IVR was not correlated with the final BCVA. CONCLUSION: Intravitreal ranibizumab for the treatment of exudative age-related macular degeneration is effective for stabilizing vision in patients with PED, but it may be better tolerated in patients with serous PED. Although it may be important to consider the type of PED to predict the visual acuity in patients treated by IVR, the anatomical response of the PED may not correlate directly with the visual outcome.

Internal limiting membrane contrast after staining with indocyanine green and brilliant blue G during macular surgery.

PURPOSE: To evaluate the difference in color contrast by performing a color contrast ratio (CR) analysis and resulting visibility of the internal limiting membrane (ILM) when stained with indocyanine green and brilliant blue G (BBG) during macular surgery by performing a color CR analysis. METHODS: The authors analyzed 40 consecutive cases in which vitrectomy with ILM removal was performed to treat a macular hole or an epiretinal membrane. The surgical procedure was performed in 21 patients (21 eyes) after staining with indocyanine green and in 19 patients (19 eyes) after staining with BBG. The color CRs were estimated based on digital analysis of the red, green, and blue data of the digital images captured, and the CRs obtained with the two dyes were compared. RESULTS: Color contrast analysis was performed in all 40 eyes, in which the ILM was removed after staining with indocyanine green or BBG, and the CRs were estimated in every eye. The CR (mean ± SD) obtained with indocyanine green and BBG was 4.3 ± 0.3 and 2.4 ± 0.1, respectively. Indocyanine green provided a significantly higher CR than BBG (P = 0.015). CONCLUSION: Digital color contrast analysis can be used to evaluate the visibility of digital images, and it may be useful when choosing the dye to use for staining the ILM better.

Diaphyseal tibiofibular synostosis in a runner.

Diaphyseal tibiofibular synostosis is a very rare cause of shin and ankle pain. A 35-year-old male presented with complaints of left shin and ankle pain of 3 years duration that was sometimes worse after running a few miles. One year before presenting to our hospital, the actual cause for his pain was missed when only lumbar radiographs were taken at another institution. A full-length tibia film revealed a diaphyseal tibiofibular synostosis at our hospital. The presence of a synostosis should alert the surgeon to search for the various abnormalities usually associated with this condition. Magnetic resonance imaging and enhanced 3-dimensional computed tomography are essential to rule out the possibility of a neoplastic process and to determine its relation to the neurovascular structures. Simple excision of the synostosis can provide excellent symptomatic relief with a minimal risk of complications.

CSF P-Tau181 and Other Biomarkers in Patients With Neuronal Intranuclear Inclusion Disease.

BACKGROUND AND OBJECTIVES: CSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer disease (AD) and has recently been regarded to reflect ß-amyloid and/or p-tau deposition in the AD brain. Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by intranuclear inclusions in neurons, glial cells, and other somatic cells. Symptoms include dementia, neuropathy, and others. CSF biomarkers were not reported. The objective of this study was to investigate whether CSF biomarkers including p-tau181 are altered in patients with NIID. METHODS: This was a retrospective observational study. CSF concentrations of p-tau181, total tau, amyloid-beta 1-42 (Aß42), monoamine metabolites homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) were compared between 12 patients with NIID, 120 patients with Alzheimer clinical syndrome biologically confirmed based on CSF biomarker profiles, and patients clinically diagnosed with other neurocognitive disorders (dementia with Lewy bodies [DLB], 24; frontotemporal dementia [FTD], 13; progressive supranuclear palsy [PSP], 21; and corticobasal syndrome [CBS], 13). Amyloid PET using Pittsburgh compound B (PiB) was performed in 6 patients with NIID. RESULTS: The mean age of patients with NIID, AD, DLB, FTD, PSP, and CBS was 71.3, 74.6, 76.8, 70.2, 75.5, and 71.9 years, respectively. CSF p-tau181 was significantly higher in NIID (72.7 ± 24.8 pg/mL) compared with DLB, PSP, and CBS and was comparable between NIID and AD. CSF p-tau181 was above the cutoff value (50.0 pg/mL) in 11 of 12 patients with NIID (91.7%). Within these patients, only 2 patients showed decreased CSF Aß42, and these patients showed negative or mild local accumulation in PiB PET, respectively. PiB PET scans were negative in the remaining 4 patients tested. The proportion of patients with increased CSF p-tau181 and normal Aß42 (A-T+) was significantly higher in NIID (75%) compared with DLB, PSP, and CBS (4.2%, 4.8%, and 7.7%, respectively). CSF HVA and 5-HIAA concentrations were significantly higher in patients with NIID compared with disease controls. DISCUSSION: CSF p-tau181 was increased in patients with NIID without amyloid accumulation. Although the deposition of p-tau has not been reported in NIID brains, the molecular mechanism of tau phosphorylation or secretion of p-tau may be altered in NIID.

Evaluation of microincision vitrectomy wounds made with microvitreoretinal blade or beveled trocar by swept source optical coherence tomography.

PURPOSE: To compare the wound closure and postoperative hypotony after sclerotomy with a microvitreoretinal (MVR) blade trocar with those with a beveled trocar for microincision vitrectomy. METHODS: The study design is a prospective randomized control study. Forty eyes of 40 patients with an epiretinal membrane that underwent 25-gauge transconjunctival sutureless vitrectomy were studied. One hundred and twenty sclerotomies were observed by swept source optical coherence tomography at 3 hours and at 1, 3, 7, and 14 days postoperatively. A closure of the sclerotomy site was defined as an absence of a scleral gap in the swept source optical coherence tomography images. The closure rate of the sclerotomies, intraocular pressures, and the incidence of complications were compared between the sclerotomies performed with an MVR blade and those with a beveled trocar. RESULTS: The rates of sclerotomy closure at 3 hours and at 1, 3, 7, and 14 days were 30.0%, 38.3%, 43.3%, 66.7%, and 95.0% with the MVR blade trocar and 21.7%, 26.7%, 36.7%, 53.3%, and 86.7% with the beveled trocar, respectively (P > 0.05 for all, Fisher exact test). The mean size of the sclerotomy was 143.9 ± 45.5 µm with the MVR blade and 158.7 ± 61.7 µm with the beveled trocar (P = 0.55, Mann-Whitney U test). The mean angle of the sclerotomies was significantly larger with the MVR blade trocar (48.9° vs. 45.8°; P = 0.049, Mann-Whitney U test). No significant difference in the speed of wound closure was found between the 2 groups (P = 0.174). Hypotony was not observed in both groups, and the intraocular pressure did not differ significantly between the two groups. CONCLUSION: The absence of significant better rates of self-sealing and faster recovery of sclerotomies made with the MVR blade trocar and the bevel trocar indicates that these factors are not related to the type of trocar.

Long-term outcome of preoperative disrupted inner/outer segment junctions assessed using spectral-domain optical coherence tomography in patients with idiopathic epiretinal membrane.

PURPOSE: To evaluate the anatomic and functional outcomes as assessed by spectral-domain optical coherence tomography in patients with a preoperative disrupted or irregular photoreceptor inner/outer segment (IS/OS) junction who underwent idiopathic epiretinal membrane (ERM) surgery and were followed for at least 2 years. METHODS: We retrospectively studied all of the patients with idiopathic ERM who had a preoperative disrupted IS/OS junction and were scheduled to undergo a transconjunctival 25-gauge vitrectomy between September 2007 and October 2009. All of the patients who had a 2-year or longer follow-up period were included in the study. The best-corrected visual acuity (BCVA) and structural changes in the IS/OS junction were examined before and 3, 6, 12, and 24 months after surgery. Furthermore, patients were divided into two groups based on whether the preoperative disrupted IS/OS junction had been caused by a lamellar macular hole (LMH type) or swelling as a result of ERM traction (S type). Morphologic changes in the IS/OS junctions of each type were also investigated. RESULTS: A total of 17 patients were identified in this study. Overall, a significantly better postoperative BCVA was seen after surgery; in particular, the BCVA at 24 months was significantly better than that at 12 months (p=0.018). Although the disrupted IS/OS junction appeared normal in 1 out of 17 eyes at 12 months, 7 eyes appeared normal at 24 months. These 7 eyes showed significant postoperative improvement in BCVA compared with the remaining 10 eyes (p=0.045, p=0.021, p=0.019, and p=0.015 at 3, 6, 12, and 24 months, respectively). The preoperative disrupted IS/OS junction was classified as LMH type in 8 eyes and as S type in 9 eyes. The LMH type, rather than the S type, tended to show a persistently disrupted IS/OS junction at 24 months, although the difference was not significant. CONCLUSION: Anatomic and functional recovery of preoperative disrupted IS/OS junctions can be acquired even after more than 1 year postoperatively. However, eyes with persistent irregularities of the IS/OS junction at a 2-year follow-up, especially those with LMH type irregularities, might have a limited visual improvement.

Effect of intravitreal gas tamponade for sutureless vitrectomy wounds: three-dimensional corneal and anterior segment optical coherence tomography study.

PURPOSE: To investigate the effect of gas tamponade on wound closure and postoperative hypotony by comparing fluid-filled and gas-filled eyes after 25-gauge sutureless vitrectomy using three-dimensional corneal and anterior segment optical coherence tomography. METHODS: Twenty-four eyes of 24 patients who underwent a 25-gauge transconjunctival sutureless vitrectomy were included in this prospective study. A total of 72 scleral wounds were observed using three-dimensional corneal and anterior segment optical coherence tomography at 3 hours and at 1, 3, 7, and 14 days postoperatively. Scleral wound closure was defined as the absence of a scleral gap at the sclerotomy site, as observed using three-dimensional corneal and anterior segment optical coherence tomography. The rate of wound closure, intraocular pressure, and the incidence of complications were compared between the fluid- and gas-filled eyes. RESULTS: The rates of scleral wound closure at 3 hours and at 1, 3, 7, and 14 days were 26.2%, 28.6%, 35.7%, 52.4%, and 85.7% in fluid-filled eyes and 53.3%, 73.3%, 76.7%, 83.3%, and 93.3% in gas-filled eyes; these rates were significantly higher for the gas-filled eyes. The intraocular pressure was significantly higher in the gas-filled eyes than in the fluid-filled eyes on postoperative Day 1 but did not differ significantly between the 2 groups on postoperative Day 3 and thereafter. CONCLUSION: Three-dimensional corneal and anterior segment optical coherence tomography provided clear images of 25-gauge sutureless vitrectomy wounds and revealed that the sclerotomies closed faster in gas-filled eyes than in fluid-filled eyes. Thus, gas tamponade might be effective for the closure of sutureless vitrectomy wounds.

Preoperative inner segment/outer segment junction in spectral-domain optical coherence tomography as a prognostic factor in epiretinal membrane surgery.

PURPOSE: To evaluate the macular structure on spectral-domain optical coherence tomographic (SD-OCT) images to predict the outcome of surgery for idiopathic epiretinal membrane. METHODS: Forty-five eyes of 45 consecutive patients with idiopathic epiretinal membrane who had a preoperative visual acuity of ≤ 20/32 and were scheduled to undergo a transconjunctival 25-gauge vitrectomy were involved in this prospective cohort study. The best-corrected visual acuity (BCVA) and SD-OCT images of the fovea were examined before the surgery and at 3, 6, and 12 months after the surgery. Associations between the visual acuity parameters and the preoperative SD-OCT features, including the morphology of the photoreceptor inner segment/outer segment junction, macular thickness, presence/absence of retinal cysts, and presence/absence of a macular pseudohole, were investigated as predictors of the outcome of the surgery. The main outcome measures were the association between the macular microstructure on preoperative SD-OCT images and the visual acuity parameters, such as the BCVA, at 12 months after the surgery (postoperative BCVA) and the difference between the preoperative visual acuity and the postoperative BCVA. RESULTS: A total of 45 patients were enrolled in this study. The postoperative visual acuity was significantly better for the eyes with an intact inner segment/outer segment junction on the preoperative SD-OCT images than for those with an irregular or a disrupted inner segment/outer segment junction on the images (P < 0.001). Better preoperative visual acuity was associated with better visual acuity at 12 months and a lesser degree of improvement in the visual acuity (P < 0.001, respectively). CONCLUSION: The presence of an intact inner segment/outer segment junction on the preoperative SD-OCT images was found to be an important predictor of better visual recovery and better postoperative BCVA after epiretinal membrane surgery.

Results of one-year follow-up examinations after intravitreal bevacizumab administration for chronic central serous chorioretinopathy.

BACKGROUND: our purpose was to report the results of 1-year follow-up examinations after intravitreal bevacizumab injection for the treatment of chronic central serous chorioretinopathy (CSC). METHODS: five eyes in 5 patients with chronic CSC were intravitreally injected with 1.25 mg/0.05 ml of bevacizumab. The need for retreatment was evaluated if spectral-domain optical coherence tomography showed the presence of subretinal fluid at the time of a 1-month follow-up examination. Best-corrected visual acuity and central foveal thickness were compared between baseline and 1 year after the first injection. RESULTS: the mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity improved from 0.23 ± 0.46 to 0.17 ± 0.47 and the mean central foveal thickness significantly decreased from 323 ± 98 microm to 171 ± 63 microm (p < 0.05). CONCLUSION: The intravitreal injection of bevacizumab is well tolerated in maintaining vision and reducing serous retinal detachment in patients with chronic CSC, as evaluated at a 1-year follow-up examination.

Aseptic Meningitis-retention Syndrome Associated with Tocilizumab in a Patient with Idiopathic Multicentric Castleman Disease.

This is the first report of tocilizumab-associated meningitis-retention syndrome in a patient with idiopathic multicentric Castleman disease. A 57-year-old man presented with headache, nuchal rigidity, impaired consciousness, pyramidal tract signs and urinary retention. A cerebrospinal fluid examination revealed increased cell counts and protein levels. These symptoms were improved by intravenous methylprednisolone. Tocilizumab-associated meningoencephalitis has been reported in patients with rheumatoid arthritis and juvenile idiopathic arthritis but not with multicentric Castleman disease. This case presents evidence of the increased probability of meningitis as a neurological complication of tocilizumab administration.

Results of 1-year follow-up examinations after intravitreal bevacizumab administration for idiopathic choroidal neovascularization.

PURPOSE: The purpose of this study was to report the results of 1-year follow-up examinations after intravitreal bevacizumab injection for the treatment of idiopathic choroidal neovascularization. METHODS: Seven eyes in 7 patients with idiopathic choroidal neovascularization were intravitreally injected with 1.25 mg/0.05 mL of bevacizumab. The need for retreatment was evaluated if spectral-domain optical coherence tomography showed intraretinal edema or subretinal fluid at the time of a 1-month follow-up examination. Fluorescein angiography was performed 1 year after the first injection. The primary outcome measures were best-corrected visual acuity and central foveal thickness using spectral-domain optical coherence tomography. RESULTS: All 7 eyes were assessed at a 1-year follow-up examination. The mean number of injections per eye was 2.7. The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved significantly from 0.31 +/- 0.29 to 0.15 +/- 0.38 (P < 0.05). The mean central foveal thickness decreased from 332 +/- 83 microm to 261 +/- 66 microm (P < 0.01). Fluorescein angiography showed no leakage at 1 year in all eyes. All patients whose best-corrected visual acuity improved by > or =0.2 logarithm of the minimum angle of resolution had a visual acuity of > or =20/40 when first injected at baseline. CONCLUSION: The intravitreal injection of bevacizumab is effective for stabilizing or improving vision in patients with idiopathic choroidal neovascularization, as evaluated at a 1-year follow-up examination. In particular, this treatment may be well tolerated in patients with a visual acuity of > or =20/40 at baseline. Additional investigations are needed to assess the long-term safety and the optimal protocol for intravitreal bevacizumab administration.