Late Dislocation of In-the-Bag Intraocular Lens in Three Patients with Multiple Chorioretinal Atrophy Associated with Sarcoidosis.

PURPOSE: A late dislocation of an in-the-bag intraocular lens (IOL) is strongly associated with pseudoexfoliation and less with retinitis pigmentosa, prior vitreoretinal surgery, and uveitis. We present our findings of late in-the-bag IOL dislocation in three patients with multiple chorioretinal atrophy associated with sarcoidosis. METHODS: Observational study of three elderly female Japanese patients with a history of uveitis from sarcoidosis who presented with a late dislocation of an in-the-bag IOL. RESULTS: The late in-the-bag IOL dislocation occurred in the convalescent/quiescent stage of the sarcoidosis. Peripheral multifocal chorioretinal atrophy was the main manifestation in all patients who were diagnosed with definite or presumed sarcoidosis. The dislocated IOLs were successfully removed and new IOLs were implanted with scleral suture fixation followed by no remarkable active uveitis. CONCLUSION: Clinicians should be aware that patients with peripheral multifocal chorioretinal atrophy associated with sarcoidosis can have a late in-the-bag IOL dislocation.

Macular Hole Formation in Eye After Cryotherapy and Intravitreal Bevacizumab Treatment for Vasoproliferative Tumor.

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.

Stereopsis After Unilateral Macular Hole Surgery with Internal Limiting Membrane Peeling.

PURPOSE: We have shown distinct morphological changes of the foveal retina such as horizontally asymmetrical retinal thicknesses and displacements of the fovea toward the optic disc after successful idiopathic macular hole (MH) closure by MH surgery with internal limiting membrane (ILM) peeling. The purpose of this study was to determine whether these morphological changes will alter the stereoacuity. SETTING: This was a non-randomized, retrospective study conducted on patients who underwent MH surgery at the Matsumoto Dental University Hospital, Nagano, Japan. METHODS: Forty patients (22 women, 18 men) who underwent MH surgery with ILM peeling for a unilateral MH were studied. At >6 months after the PPV, the stereoacuity was measured with the Titmus stereotest (TST) and the TNO stereotest (TNO). The relationship between the stereoacuity and the age, MH size, best-corrected visual acuity (BCVA), foveal retinal thickness, and amount of nasal shift of the retina was determined. RESULTS: The mean postoperative BCVA was -0.05 ± 0.11 logarithm of the minimum angle of resolution (logMAR) units. The percentage of cases with good stereoacuity of ≤100 sec of arc was 87.5% with the TST and ≤240" was 90% with the TNO test. A better stereoacuity was significantly correlated with a younger age (r = 0.36, P <0.05; with TNO), smaller MH (r = 0.51, P < 0.001, with TST), better postoperative BCVA (r = 0.43 P <0.01 with TST; r = 0.49, P <0.01 with TNO), but not with the parafoveal retinal thickness or degree of nasal shift. CONCLUSION: The postoperative stereopsis is relatively good in patients with better postoperative BCVA after MH surgery with ILM peeling, even though foveal morphological changes had occurred.

Comparisons of foveal thickness and slope after macular hole surgery with and without internal limiting membrane peeling.

BACKGROUND: We have shown that the foveal contour was asymmetrical after idiopathic macular hole (MH) closure by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling. The purpose of this study was to determine whether these morphological changes differ in eyes after PPV without ILM peeling. METHODS: Ten eyes of 10 patients that underwent PPV without ILM peeling and 12 eyes of 11 patients with ILM peeling were studied. The MH in all eyes was <400 µm in diameter. Six months after the PPV, the macular thickness and foveal slope around the closed MH were determined by spectral-domain optical coherence tomography. The thickness of the ganglion cell complex was measured by another spectral-domain optical coherence tomography instrument >6 months after the surgery. RESULTS: The mean parafoveal retinal thickness in the non-peeled group was 367.1 µm in the nasal (N), 353.0 µm in the temporal (T), 366.9 µm in the superior (S), and 357.3 µm in the inferior (I) sectors. The T, S, and I sectors were significantly thicker than the corresponding sectors in the ILM peeled group (p=0.0008, 0.003, and 0.03, respectively). The mean ganglion cell complex was thicker not only in the N sector but also in the T sector in the non-peeled group. The mean retinal slopes in the non-peeled group (N, 40.2°; T, 37.6°; S, 41.2°; I, 39.5°) were flatter than those in the peeled group (N, 52.3°; T, 43.6°; S, 50.8°; I, 51.9°; p=0.009, 0.09, 0.008, and 0.017, respectively). CONCLUSION: The symmetrical fovea after MH surgery in the non-ILM peeled eyes indicates that the asymmetrical fovea after ILM peeling was probably due to the ILM peeling.

Displacement of fovea toward optic disk after macular hole surgery with internal limiting membrane peeling.

PURPOSE: The purpose of this study was to demonstrate a displacement of the foveal depression toward the optic disk after idiopathic macular hole (MH) surgery with internal limiting membrane (ILM) peeling. METHODS: Two patients with a unilateral MH developed an MH in the fellow eyes. Vitrectomy with ILM peeling was performed on the fellow eye to close the MH. Images of spectral-domain optical coherence tomography (SD-OCT) were used to measure the disk-to-fovea distances pre MH formation, after MH formation, and 6 months after the closure of the MH. RESULTS: The disk-to-fovea distance was shorter at 6 months than after the development of the MH (4,109 µm and 4,174 µm in Case 1 and 4,001 µm and 4,051 µm in Case 2). CONCLUSION: These results indicate that the fovea moves nasally after the MH surgery with ILM peeling.

Transient Increase of Retinal Nerve Fiber Layer Thickness after Vitrectomy with ILM Peeling for Idiopathic Macular Hole.

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.

Asymmetrical steepening of the foveal contour after macular hole surgery with internal limiting membrane peeling.

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.

Retinal angiomatous proliferation in an eye with cuticular drusen.

PURPOSE: To report the presence of retinal angiomatous proliferation (RAP) in an eye with cuticular drusen detected by fluorescein and indocyanine green angiography by confocal scanning laser ophthalmoscopy and by spectral-domain optical coherence tomography (SD-OCT). METHODS: Case report of a 65-year-old Japanese woman with cuticular drusen. RESULTS: At her first ophthalmic examination, her visual acuity was 20/20 in both eyes. An ophthalmoscopy showed many small subretinal pigment epithelial deposits in both eyes. These deposits had a 'saw-tooth pattern' in the SD-OCT images. During the follow-up examination, retinal hemorrhages were observed, and fluorescein angiography showed a 'stars-in-the-sky' appearance and intraretinal neovascularization. The patient was diagnosed with cuticular drusen associated with RAP. CONCLUSION: We suggest that the cuticular drusen were associated with RAP, so periodic follow-up examinations are needed for patients with cuticular drusen for the early detection and treatment of RAP.

Retinal involvement in uveitis associated with Hodgkin disease.

PURPOSE: To describe a patient with Hodgkin disease with posterior uveitis who also had a thinning of the retina and an antiretinal autoantibody in his serum. METHODS: Our patient was a 58-year-old man who had been diagnosed with Hodgkin disease. He had a complete ophthalmologic examination including fluorescein angiography, electroretinography, perimetry, and spectral-domain optical coherence tomography. A search for antiretinal antibodies in the serum was made by Western blot analysis, and the retinal sites reactive to the antibodies were determined by immunohistochemistry. RESULTS: The ocular signs were mild cellular infiltration in the anterior chamber and vitreous, and small, round chorioretinal lesions in the peripheral retina. The electroretinograms were slightly reduced. Small ring-like scotomas were detected in the Goldmann visual fields. An antiretina-specific 116-kDa antibody was detected in the serum by Western blot analysis, and the antibody reacted with the ganglion cell and inner nuclear layers of mice retinas. Although the visual acuities were maintained for over eight years, the macular thickness measured in the spectral-domain optical coherence tomography images was reduced. CONCLUSION: The presence of an antiretinal autoantibody, granulomatous uveitis, and retinal thinning in a patient with Hodgkin disease suggests that the patient had a granulomatous uveitis associated with Hodgkin disease or lymphoma-associated uveitis with retinal involvement.

Retinal thickness in eyes with idiopathic macular hole after vitrectomy with internal limiting membrane peeling.

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.

REM sleep behavior disorder in Japanese patients with Parkinson's disease: a multicenter study using the REM sleep behavior disorder screening questionnaire.

REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson's disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson's Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p < 0.01). As to the major autonomic dysfunctions, severe constipation was significantly more frequent in PD patients with RBD than in those without it (p < 0.01). The RBD symptoms of 53 patients (39.0%) preceded the onset of PD motor symptoms. The median interval from the onset of RBD symptoms to PD motor symptoms was 17.5 years, and 3 patients had intervals of over 50 years. This large-scale multicenter study revealed that RBD is a frequent non-motor symptom in Japanese patients with PD, which may precede the onset of motor symptoms. Moreover, RBD that increases with the duration and severity of PD may be associated with autonomic dysfunction.

Retinoschisis detected by spectral-domain optical coherence tomography in von hippel-lindau disease.

PURPOSE: To report the presence of retinoschises in a case of von Hippel-Lindau disease detected by spectral-domain optical coherence tomography. METHODS: Case report of a 23-year-old man with von Hippel-Lindau disease who was seen for a regular follow-up examination. RESULTS: Ophthalmoscopy showed several retinal capillary hemangioblastomas in both eyes. Spectral-domain optical coherence tomography showed retinoschises around the retinal capillary hemangioblastoma and also around the feeder and draining vessels of the peripheral larger hemangioblastoma. The retinoschises were found under the internal limiting membrane and also in the inner and outer retinal layers. Intraretinal columns were observed in the retinoschises. CONCLUSION: Our observations show that retinoschises can develop in eyes with von Hippel-Lindau disease. The extensiveness of the retinoschises suggests that the retina is fragile in von Hippel-Lindau disease.

Cancer-associated retinopathy in a patient with seminoma.

PURPOSE: The purpose of this study was to report our findings on a patient with cancer-associated retinopathy who had seminoma. METHODS: A 43-year-old man, who had been diagnosed with Stage 1 seminoma, complained of blurred vision. Fundus examination revealed attenuated retinal arteries, mild optic disk pallor, and a thinning of the outer nuclear layer. Ring scotomas were found in the visual fields of both eyes. The amplitudes of the electroretinograms were moderately reduced. The patient's serum was analyzed for antibodies. RESULTS: Antibodies against recoverin, Hu, and Ma-2 antigens were not detected. However, Western blots of the serum detected 2 bands at 41 and 64 kDa. The 41-kDa band was an anti-retina-specific antibody. Immunoreactivity was identified in the photoreceptor layer of mice retinas. From these findings, we diagnosed the patient with cancer-associated retinopathy. The visual functions remained stable after the removal of the primary lesion at an early stage, treatment with steroids, and intravenous immunoglobulin. CONCLUSION: This is the first case of cancer-associated retinopathy because of seminoma. The progression of the disease was reduced by removing the seminoma at an early stage, treatment with steroids, and intravenous immunoglobulin.

Perfusion IMP-SPECT shows reversible abnormalities in GABA(B) receptor antibody associated encephalitis with normal MRI.

A new subtype of autoimmune encephalitis associated with antibodies against GABA(B) receptor was recently identified. Although immune-mediated functional abnormalities are suggested for the pathogenesis, functional brain imaging such as perfusion SPECT has not been documented. A 62-year-old woman with anti-GABA(B) receptor associated encephalitis underwent (123)I-IMP SPECT in the beginning and after methylprednisolone pulse therapy. Three-dimensional stereotactic surface projection analysis was used to evaluate the cortical distribution of perfusion abnormality. The patient presented with clinical features of subacute limbic encephalitis. Antibodies to GABA(B) receptor were identified in her serum and cerebrospinal fluid (CSF), but no tumor was detected. Despite normal magnetic resonance imaging (MRI) findings, the first SPECT revealed hypoperfusion of the frontal, parietal and medial temporal lobes, as well as thalamus, and cerebellum. These areas are known to contain high levels of GABA(B) receptors. In contrast, the SPECT revealed hyperperfusion in the motor strip and left temporal lobe, which are areas related to some of the patient's symptoms, including seizures, orolingual dyskinesia, and Wernicke aphasia. After treatment with pulses of methylprednisolone, the neuropsychiatric symptoms resolved and the SPECT findings showed substantial improvement in most of these regions. In conclusion, the findings suggest that immunotherapy improved the cortical dysfunction mediated by GABA(B) receptor antibodies.

Microperimetric determination of retinal sensitivity in areas of dissociated optic nerve fiber layer following internal limiting membrane peeling.

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.

{mu}-Crystallin, new candidate protein in endotoxin-induced uveitis.

PURPOSE. micro-Crystallin (CRYM) is a major taxon-specific lens protein. The purpose of this study was to investigate the function of CRYM in eyes of mice with endotoxin-induced uveitis (EIU). METHODS. EIU was induced by an injection of a lipopolysaccharide (LPS) into the footpad of male C57BL/6J, CRYM knockout (CRYM(-/-)), and wild-type (CRYM(+/+)) mice. The expression of CRYM in the iris-ciliary body (ICB) was investigated by Western blot analyses and real-time RT-PCR at 12 hours and 1, 3, and 5 days after the LPS injection. The number of cells that had infiltrated the anterior chamber (AC) of the CRYM(+/+) mice was compared to that in the CRYM(-/-) mice at 1, 3, 5, and 7 days. The expressions of the mRNA of interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and granulocyte macrophage-colony stimulating factor (GM-CSF) in the ICB of the two groups of mice were compared. RESULTS. The mRNA of CRYM was upregulated at 12 hours after LPS injection, and CRYM protein increased at 3 days. The number of inflammatory cells in the AC of the CRYM(-/-) mice was not significantly different on day 1 from that in the CRYM(+/+) mice, but was significantly lower (17.9 +/- 1.6 vs. 27.1 +/- 2.4 cells/section) on day 5. Expression of the mRNA of IL-1alpha and -6 in the CRYM(-/-) mice was significantly lower than that in the CRYM(+/+) mice on day 5. CONCLUSIONS. CRYM plays an important role in the development of the second peak of murine EIU.

Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen.

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 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. 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 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). INTERPRETATION: 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. FUNDING: National Institutes of Health.

Cytokine and molecular analyses of intraocular lymphoma.

PURPOSE: The authors investigate the efficacy of using the cytokine levels and clonal heavy-chain immunoglobulin (IgH) gene rearrangements in the vitreous as adjunctive tools to diagnose intraocular lymphoma (IOL). METHODS: The IL-10 and IL-6 levels and IgH gene rearrangements were analyzed in vitreous samples from 8 cases of IOL and in 14 uveitis patients. RESULTS: The level of IL-10 with an IL-10/IL-6 ratio > 1 was significantly higher in all eyes with IOL. B-cell monoclonality was detected in only 5 of 8 eyes with IOL. CONCLUSIONS: The measurements of the levels of cytokines are valuable as a reliable biomarker.