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Summary Background Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. Methods 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABAB1 or GABAB2 receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. Findings All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABAB receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABAB receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0·005). Low levels of GABAB1 receptor antibodies were identified in two of 104 controls (p<0·0001). Interpretation GABAB receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies. Funding National Institutes of Health.

Purpose To investigate the effects of a dissociated optic nerve fiber layer (DONFL) on retinal sensitivity. Methods The medical records of 17 eyes with an idiopathic macular hole that underwent vitrectomy and internal limiting membrane (ILM) peeling were examined. All patients underwent a complete ophthalmic examination, color fundus photography, and argon blue-filter photography to determine whether a DONFL was present. The retinal function was assessed by comparing the mean retinal sensitivities in the DONFL area to those in the surrounding normal retina by static microperimetry >3 months after the surgery. The retinal sensitivities of eight regions nearest the fovea and all at the same distance from it were determined in all patients. We divided the retinal sensitivities in the two areas, that is, inside and outside the area of the DONFL, and compared each mean value. Results Following the initial vitrectomy, the macular holes of all eyes were closed. The mean retinal sensitivities in the area of the DONFL did not differ significantly from those in the surrounding areas ( P = 0.60). Conclusions DONFL associated with ILM peeling does not alter retinal function in the area of the DONFL as it does with a nerve fiber layer defect.

Purpose We have previously shown that the thickness of the parafoveal retina was asymmetrical in spectral-domain optical coherence tomographic (SD-OCT) images after idiopathic macular hole (MH) closure by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling. The aim of this study was to determine whether the foveal slopes around the closed MH were also asymmetrical. Methods Forty-three eyes with an MH treated with PPV with ILM peeling at Matsumoto Dental University Hospital were studied. The foveal slope was determined with ImageJ software in both the horizontal and vertical images obtained by SD-OCT at 6 months after the surgery. The possible related factors were also compared. Results The mean angles of the foveal slopes of the nasal, superior, inferior, and temporal sectors were 31.4° ± 6.2°, 31.2° ± 5.4°, 31.6° ± 7.4°, and 29.9° ± 6.6°, respectively, in the fellow eyes. The corresponding values in the operated eyes were significantly steeper at 50.4° ± 9.1°, 46.9° ± 11.3°, 48.6° ± 11.3°, and 41.3° ± 11.2°, respectively ( P   <  0.00001). Both the nasal and inferior slopes were significantly steeper than the temporal slopes of the same operated eye ( P   =  0.002 and P   =  0.023, respectively). There was no significant correlation between each slope and the visual acuity, MH size, area of peeled ILM, postoperative parafoveal retinal thickness, defect of the retinal outer layers, disc-foveal distance, stage, and use of dye for ILM peeling. Conclusions Although the postoperative foveal contour was markedly changed asymmetrically, the significance of the change was not determined.

To report a case of a full-thickness macular hole (MH) that developed after cryotherapy and intravitreal bevacizumab injection (IVB) to treat a retinal vasoproliferative tumor (VPT). Case report of a man with a retinal VPT. A 64-year-old Japanese man complained of blurred vision in his right eye. At the initial examination, his best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/20 in the left eye. Ophthalmoscopy showed a VPT in the lower peripheral retina of the right eye. An exudative retinal detachment and hard exudates were seen around the tumor. Cryotherapy and intravitreal injections of bevacizumab (IVB) were performed. Although the exudative changes were reduced, a MH developed two months after the initial IVB treatment. He underwent 25-gauge pars plana vitrectomy, and the MH was closed. His postoperative BCVA was 20/32 and the VPT was inactive. The reduced BCVA was due to damage of the outer retinal layers. Our findings indicate that cryotherapy and IVB are effective treatments for VPT although the possibility of developing a MH should be considered.

Purpose. The purpose of this study was to determine the long-term changes in the circumpapillary retinal nerve fiber layer (RNFL) thickness following macular hole surgery with internal limiting membrane (ILM) peeling combined with phacoemulsification. Methods. Thirty-eight eyes of 37 patients who had pars plana vitrectomy (n=36) between 2010 and 2014 were studied. The average thicknesses of the global and the six sectors of the RNFL were determined before and at 1, 3, 6, 12, and 24 (n=22) months (M) after the surgery by spectral-domain optical coherent tomography. The postoperative mean RNFL thickness at each time was compared to that before the surgery by paired t-tests. Results. The RNFL of the operated eyes was significantly thicker at 1 month (1 M) and 3 M in all but the inferior-nasal sectors. The significant increase remained until 12 M in the superior-temporal and superior-nasal sectors. In addition, the RNFL was also significantly thicker in the temporal-inferior sector at 12 M based on the findings in 38 eyes. Conclusions. The postoperative RNFL was thicker in all but the nasal-inferior sector for at least 12 M after surgery. This prolonged increase of the RNFL thickness may indicate damage and mild edema of the RNFL.

To describe the morphology of the retina at the convalescent stage of acute zonal occult outer retinopathy (AZOOR) from images obtained by spectral domain optical coherence tomography (SD-OCT). The visual fields, electroretinograms (ERGs), and OCT images were reviewed in two women aged 24 and 33 years. The patients were followed for one and four years, respectively. In both cases, the anterior and posterior segments were almost normal, although both patients had a sudden unilateral vision decrease and photopsia. Goldmann perimetry revealed enlarged blind spots and scotomas. The ERGs were reduced in both cases. SD-OCT showed that the junction of the inner and outer segment, the IS/OS line, of the photoreceptors was irregular or lost in the affected retinas. The retina in these areas was thinner due to a decrease in the thickness of both the outer nuclear layer (ONL) and inner nuclear layer (INL) in Case 2. The decrease in retinal thickness at the convalescent stage of AZOOR is most likely due to a shortening of not only the photoreceptors and ONL but also to a thinning of the INL in a severe case.

Some encephalitides or seizure disorders once thought idiopathic now seem to be immune mediated. We aimed to describe the clinical features of one such disorder and to identify the autoantigen involved. 15 patients who were suspected to have paraneoplastic or immune-mediated limbic encephalitis were clinically assessed. Confocal microscopy, immunoprecipitation, and mass spectrometry were used to characterise the autoantigen. An assay of HEK293 cells transfected with rodent GABA(B1) or GABA(B2) receptor subunits was used as a serological test. 91 patients with encephalitis suspected to be paraneoplastic or immune mediated and 13 individuals with syndromes associated with antibodies to glutamic acid decarboxylase 65 were used as controls. All patients presented with early or prominent seizures; other symptoms, MRI, and electroencephalography findings were consistent with predominant limbic dysfunction. All patients had antibodies (mainly IgG1) against a neuronal cell-surface antigen; in three patients antibodies were detected only in CSF. Immunoprecipitation and mass spectrometry showed that the antibodies recognise the B1 subunit of the GABA(B) receptor, an inhibitory receptor that has been associated with seizures and memory dysfunction when disrupted. Confocal microscopy showed colocalisation of the antibody with GABA(B) receptors. Seven of 15 patients had tumours, five of which were small-cell lung cancer, and seven patients had non-neuronal autoantibodies. Although nine of ten patients who received immunotherapy and cancer treatment (when a tumour was found) showed neurological improvement, none of the four patients who were not similarly treated improved (p=0.005). Low levels of GABA(B1) receptor antibodies were identified in two of 104 controls (p<0.0001). GABA(B) receptor autoimmune encephalitis is a potentially treatable disorder characterised by seizures and, in some patients, associated with small-cell lung cancer and with other autoantibodies. National Institutes of Health.

Purpose To compare the thickness of each retinal layer in the parafoveal and perifoveal regions of eyes after successful closure of a macular hole (MH) by pars plana vitrectomy with internal limiting membrane (ILM) peeling to the corresponding areas of the normal fellow eyes. Methods Twenty-two eyes of 22 patients with an idiopathic MH who underwent PPV with ILM peeling at the Matsumoto Dental University Hospital were studied. The retinal thickness was measured manually with the volume scan mode of the Spectralis HRA + OCT (Heidelberg Engineering, Germany). Results The average postoperative parafoveal thickness of the temporal sector was 314.8 μm, and that of the corresponding area of the fellow eyes was 325.0 μm ( P  = 0.01). The parafoveal thickness of the nasal sector was 360.7 μm, and that of the fellow eyes was 339.6 μm ( P  < 0.0001). Changes in the inner retinal layer thicknesses contributed to the decreased temporal and increased nasal sectors. The perifoveal retinal thickness was significantly increased in all sectors after PPV, probably due to an increase in the outer nuclear layer thickness. Conclusions PPV with ILM peeling for MHs can cause microstructural changes in wide areas of the macula region, suggesting a loss of longitudinal support of the Müller cells.

Purpose: To report a case of a full-thickness macular hole (MH) that developed after cryotherapy and intravitreal bevacizumab injection (IVB) to treat a retinal vasoproliferative tumor (VPT). Methods: Case report of a man with a retinal VPT. Results: A 64-year-old Japanese man complained of blurred vision in his right eye. At the initial examination, his best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/20 in the left eye. Ophthalmoscopy showed a VPT in the lower peripheral retina of the right eye. An exudative retinal detachment and hard exudates were seen around the tumor. Cryotherapy and intravitreal injections of bevacizumab (IVB) were performed. Although the exudative changes were reduced, a MH developed two months after the initial IVB treatment. He underwent 25-gauge pars plana vitrectomy, and the MH was closed. His postoperative BCVA was 20/32 and the VPT was inactive. The reduced BCVA was due to damage of the outer retinal layers. Conclusion: Our findings indicate that cryotherapy and IVB are effective treatments for VPT although the possibility of developing a MH should be considered. Keywords: intravitreal bevacizumab injection, macular hole, optical coherence tomography, vasoproliferative tumor, vitrectomy