Background factors determining the time to intraocular lens dislocation.

PURPOSE: To clarify the characteristics of intraocular lens (IOL) dislocation requiring IOL suture or intraocular scleral fixation. METHODS: This retrospective consecutive case series included 21 eyes (21 patients) who required sutured or sutureless intrascleral IOL fixation following IOL extraction owing to IOL dislocation at the outpatient clinic in the Department of Ophthalmology, Saitama Red Cross Hospital, Japan, between January and December 2019. Medical records were retrospectively reviewed for background diseases, location of the dislocated IOL (intracapsular/extracapsular), insertion of a capsular tension ring (CTR), and the period from IOL insertion to dislocation. RESULTS: We included 21 eyes of 21 patients who required IOL suture or intrascleral fixation for IOL dislocation at our clinic from January to December 2019 were included. The most common background disease was pseudoexfoliation syndrome (four cases), followed by atopic dermatitis, dysplasia/dehiscence of the zonule, post-retinal detachment surgery, high myopia, and uveitis (three cases each). At the time of dislocation, the IOLs were either intracapsular (16 cases, including 3 cases with CTR insertion) or extracapsular (5 cases). The time from IOL insertion to IOL dislocation was 13.7 ± 8.1 years (maximum: 31.3 years, minimum: 1.7 years). CONCLUSIONS: In this study, all 21 cases represented late IOL dislocations occurring after 3 months postoperatively. Among these late IOL dislocation cases, IOL dislocation occurred in a short-medium period of time, especially in those with CTR insertion and weakness/dehiscence of the zonule, with an average of 3 to 5 years postoperatively. We propose referring to these cases as intermediate-term IOL dislocation.

Monoclonal immunoglobulin heavy chain gene rearrangement in Fuchs' uveitis.

BACKGROUND: Fuchs' uveitis (FU) is occasionarlly complicated with heavy vitreous opacity. We have performed vitrectomy procedures to remove vitreous opacity in affected patients as part of differential diagnosis for primary vitreoretinal lymphoma (PVRL). CASE PRESENTATION: We retrospectively reviewed the clinical records of five patients who first visited the Uveitis Clinic of the University of Tokyo Hospital between 2009 and 2013, were diagnosed with FU and underwent a vitrectomy for removal of dense vitreous opacity. All were diagnosed as FU by ocular findings and elevation of Goldmann-Witmer coefficient (GWC) value for the rubella virus (RV) antibody. In examinations of the vitreous body, cytological diagnosis, elevation of IL-10/IL-6 ratio, and the kappa/lambda ratio in flow cytometry findings were negative in all cases, whereas monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was positive in 4 cases and negative in 1 case. CONCLUSIONS: Although monoclonal IgH gene rearrangement is thought to be a reliable biomarker for PVRL, a high percentage of vitreous specimens from our FU patients showed pseudo-positive results. Ophthalmologists must take care regarding possible pseudo-positive findings when performing differential diagnosis between FU and PVRL. Combinations of results of cytological diagnosis, IL-10/IL-6 ratio, kappa/lambda ratio, and IgH gene rearrangement may be necessary for a definitive diagnosis of PVRL and differentiation from FU.

Best-corrected visual acuity and frequency of ocular attacks during the initial 10 years in patients with Behçet's disease.

BACKGROUND: Recent publications have suggested considerable improvements in the clinical outcomes of ocular Behcet's disease (BD) patients. However, the long-term time course of clinical ocular features of BD in recent cases remains largely unknown. In this study, we investigated annual time-course changes of best-corrected visual acuity (BCVA) during ocular convalescent stages, as well as annual frequency of ocular attacks during the initial 10 years of follow-up in patients with BD. METHODS: We studied 75 eyes in 39 patients (31 men, eight women) with BD, who were referred to our hospital between 1980 and 1996 within 1 year after the initial ocular attack and followed them up continuously for more than 10 years. The clinical courses of BCVA at the ocular convalescent stage from the onset of ocular disease were retrospectively examined, and the numbers of ocular attacks per eye per year were determined. RESULTS: Mean BCVA was 0.59 at 1 year, 0.31 at 3 years, and 0.12 at 10 years from the onset of ocular disease, while the numbers of ocular attacks per eye were 4.1 +/- 3.1 at 1 year, 2.2 +/- 1.9 at 5 years, and 1.4 +/- 1.8 at 10 years. Ocular attacks were still observed in 33 eyes (45%) of 21 patients (54%) with BD even after 10 years. Final BCVA in 42 eyes (56%) became lower than 0.5. The major reasons for poor visual prognosis were macular atrophy (41%) and chorioretinal atrophy (26%). CONCLUSIONS: The decline of BVCA continued, and nearly half the patients still suffered from ocular attacks at 10 years after the onset of ocular BD.

Lymphocyte proliferation induced by high-affinity peptides for HLA-B*51:01 in Behçet's uveitis.

Several proteins have been proposed as candidate auto-antigens in the pathogenesis of Behçet's disease (BD). In this study, we aimed to confirm the cellular responses to candidate peptide autoantigens with high affinity for the HLA-B*51:01 molecule using computerized binding predictions and molecular dynamics simulations. We identified two new candidate peptides (HSP65PD, derived from heat shock protein-65, and B51PD, derived from HLA-B*51:01) with high-affinity to the HLA-B*51:01 binding pocket using the Immune Epitope Database for Major Histocompatibility Complex-I Binding Prediction and molecular dynamics simulations. The peptide-induced proliferation of lymphocytes from patients with BD, sarcoidosis, Vogt-Koyanagi-Harada disease (VKH) with panuveitis, systemic scleroderma (SSc) without uveitis, and healthy controls (HC) was investigated using the bromodeoxyuridine assay. The proliferative response of leukocytes to HSP65PD was significantly higher in BD (SI 1.92 ± 0.65) than that in sarcoidosis (SI 1.38 ± 0.46), VKH (SI 1.40 ± 0.33), SSc (SI 1.32 ± 0.31), and HC (SI 1.27 ± 0.28) (P = 0.0004, P = 0.0007, P < 0.0001, P < 0.0001, respectively, Mann-Whitney's U-test). The proliferative response of leukocytes to B51PD was also higher in BD than that in sarcoidosis, VKH, SSc without uveitis, and HC, whereas no significant differences were observed among the five groups in response to a control peptide derived from topoisomerase 1. A significantly higher response to HPS65PD and B51PD was observed in the HLA-B*51:01-positive patients with BD than in the HLA-B*51:01-negative patients. In conclusion, two peptides that had high affinity to HLA-B*51:01 in computerized binding prediction showed significantly higher response in HLA-B*51:01-positive patients with BD, indicating the usefulness of computerized simulations for identifying autoreactive peptides to HLAs.

Frequency of Uveitis in the Central Tokyo Area (2010-2012).

PURPOSE: To investigate the frequency of conditions of newly arrived patients with uveitis from 2010 to 2012 and compare this frequency with that since 2004. METHODS: We retrospectively analyzed clinical records of patients who visited the outpatient clinic from January 2010 to December 2012, and compared them with those from 2004-2009. RESULTS: From 2010 to 2012, 695 new patients with uveitis visited Tokyo University Hospital, with a definite diagnosis made in 431 (62.0%). The most common diagnosis was scleritis (8.3%), followed by sarcoidosis (8.1%); herpetic iridocyclitis (5.5%); Behçet disease (4.6%); Vogt-Koyanagi-Harada disease (4.0%); acute anterior uveitis (3.7%); Posner-Schlossman syndrome (3.6%); intraocular malignant lymphoma (3.0%); and bacterial endophthalmitis (1.9%). The most frequent unclassified type of uveitis was sarcoidosis-suspected (14.8%). CONCLUSIONS: When compared with years 2004-2009, the present series showed an increasing trend of intraocular malignant lymphoma, bacterial endophthalmitis, and chronic iridocyclitis, and a notable increase in chronic iridocyclitis in young girls, with decreasing trends of scleritis and Vogt-Koyanagi-Harada disease.

Initial Trabeculectomy With Mitomycin-C for Secondary Glaucoma-associated With Uveitis in Behçet Disease Patients.

PURPOSE: To examine clinical outcomes following an initial trabeculectomy with mitomycin-C for secondary glaucoma associated with uveitis in Behçet disease (BD) patients. DESIGN: Retrospective interventional case series. PATIENTS AND METHODS: Twenty-two eyes in 18 patients with uveitic glaucoma (UG) associated with Behçet disease who underwent an initial trabeculectomy with mitomycin-C between January 1996 and August 2014 were retrospectively reviewed. The main outcome measures were intraocular pressure (IOP) control, persistence of a filtering bleb, incidence of postoperative complications, and preopertaive and postoperative frequency of uveitic attacks. We analyzed persistence rates using Kaplan-Meier life tables based on 3 definitions of target IOP control (≤21, ≤18, ≤15 mm Hg) and filtering bleb persistence. RESULT: The persistence rates of postoperative IOP at ≤21, ≤18, and ≤15 mm Hg at 5 years after surgery were 76.1%, 71.5%, and 68.1%, respectively, whereas that of a filtering bleb was 54.4%. Hypotony as a postoperative complication was observed in 4 (18.2%) cases. No significant difference was observed between the preoperative and postoperative frequency of uveitic attacks (1.36±1.15 vs. 0.95±1.49 times/y, P=0.16). There was 1 case in which recurrence of uveitis after surgery caused a loss of filtering bleb, which required a reoperation. CONCLUSIONS: At 5 years after surgery, the persistence rate of postoperative IOP control (≤21 mm Hg) was 76.1% and that of a filtering bleb was 54.4%. The frequency of uveitis recurrence did not significantly increase after surgery. Attention must be paid to avoid such recurrence to maintain the filtering bleb.

Behçet's disease ocular attack score 24 and visual outcome in patients with Behçet's disease.

AIMS: To investigate the ability of the Behçet's disease ocular attack score 24 (BOS24) scoring system to predict visual acuity (VA) in patients with ocular Behçet's disease. DESIGN: This is a retrospective study. METHODS: We included 91 eyes of 50 patients with ocular Behçet's disease (33 males, 17 females) who were referred to our hospital between 1986 and 2008 with >5 years follow-up. Total BOS24 scores over a 5-year period, BOS24-5Y, were calculated as the sum of BOS24 scores for each attack over the 5-year study period for each eye. Change in VA was defined as change in best-corrected visual acuity (BCVA) from the first remission to the last remission at the end of the target period. Factors related to change in VA (age, gender, BCVA at the first remission, total number of immunosuppressive medications and total number of ocular attacks during the 5-year period and BOS24-5Y) were evaluated using a linear mixed model. RESULTS: BCVA (logarithm of the minimal angle resolution) deteriorated from 0.16±0.30 (mean±SD) to 0.21±0.37 over the 5-year study period, but there was no statistical difference. The total number of ocular attacks during the 5-year period and BOS24-5Y scores were 10.0±7.9 and 36.8±40.8, respectively. Linear mixed-model analysis revealed that BOS24-5Y was the most important index for VA deterioration, followed by BCVA at the first remission. CONCLUSIONS: BOS24-5Y was found to be a significant positive prognostic index for VA deterioration in patients with ocular Behçet's disease.

Statistical analyses of Endogenous Uveitis Patients (2007-2009) in central Tokyo area and Comparison with Previous Studies (1963-2006).

PURPOSE: To investigate the frequencies of the diseases in the new patients with uveitis during 2007-2009 and compare them with previously-reported data from the University of Tokyo Hospital. METHODS: We retrospectively analyzed the clinical records of patients who visited the outpatient clinic from January 2007 to December 2009, and compared them with those of 1963-2006. RESULTS: During 2007-2009, 468 new patients visited our hospital. Definite diagnoses were made in 63.0%. Frequent diagnoses include sarcoidosis (9.4%), Vogt-Koyanagi-Harada (VKH) disease (7.9%), herpetic iritis (6.0%), Behçet's disease (5.6%), Posner-Schlossman syndrome (4.3%), HLA-B27-associated uveitis (3.0%), and intraocular malignant lymphoma (2.8%). Compared with our former findings, the ratios of sarcoidosis, herpetic iritis, CMV retinitis, Fuch's heterochromic iridocyclitis, acute retinal necrosis and intraocular lymphoma increased, while that of Behçet's disease decreased. CONCLUSIONS: Top three uveitis during 2007-2009 were sarcoidosis, VKH disease, herpetic iritis. Reduced frequency of Behçet's disease was one of the most prominent characteristics.

Natural hypothermia immediately after transient global cerebral ischemia induced by spontaneous subarachnoid hemorrhage.

OBJECT: Spontaneous subarachnoid hemorrhage (SAH) has an aspect of graded transient global cerebral ischemia. The purpose of the present study was the documentation of sequential changes in body temperature immediately after SAH-induced transient global cerebral ischemia in humans. METHODS: Patients admitted within 12 hours after the initial onset of SAH were examined retrospectively (426 patients). Patients with unruptured cerebral aneurysms served as a control group (73 patients). Body temperature measured at the axilla on admission was analyzed. The grade of SAH was established according to the Glasgow Coma Scale (GCS): Grade I, GCS Score 15; Grade II, GCS Score 11 to 14; Grade III, GCS Score 8 to 10; Grade IV, GCS Score 4 to 7; and Grade V, GCS Score 3. The mean body temperature of patients in the control group was 36.49 +/- 0.45 degrees C (mean +/- standard deviation). The mean body temperature of patients in the SAH group who had been admitted within 4 hours of onset for Grades I to V were significantly different (p < 0.001, analysis of variance [ANOVA]): 36.26 +/- 0.7 degrees C, 59 patients; 35.98 +/-0.85 degrees C, 73 patients; 35.52 +/- 0.79 degrees C, 25 patients; 35.9 +/- 1.09 degrees C, 108 patients; and 35.56 +/- 1.14 degrees C, 73 patients, respectively. These values were significantly lower than those in control volunteers, except for patients with Grade I SAH. The reduction in body temperature was unrelated to the location of the cerebral aneurysm and was not the product of circadian rhythm. The temperatures of patients in the SAH group who were admitted beyond 4 hours after onset for each grade were significantly different (p < 0.01, ANOVA): 36.8 +/- 0.91 degrees C, 36 patients; 36.74 +/- 0.68 degrees C, 31 patients; 36.73 +/- 0.38 degrees C, three patients; 37.41 +/- 1.37 degrees C, 17 patients; and 38.9 degrees C, one patient, respectively. These values were significantly higher than those in patients admitted within 4 hours of SAH onset for all grades except Grade V, and significantly higher than control values in patients with Grades I and IV SAH. CONCLUSIONS: These results indicate that body temperature falls and then rises immediately after the SAH-induced transient global cerebral ischemia without cardiac arrest in humans. The reduction in temperature may be a natural cerebral protection mechanism that is activated shortly after ischemic insult.

[Body temperature in the super-acute phase of the cerebrovascular disorders: mainly focused on the subarachnoid hemorrhage].

BACKGROUNDS AND PURPOSE: Body temperature in the acute phase of cerebrovascular disorders(CVDs) may influence the outcome. However, the natural course of body temperature after CVDs has not yet been clarified. The purpose of this study was to elucidate the natural courses of body temperature after CVDs. PATIENTS AND METHODS: We retrospectively investigated 681 patients with CVDs(subarachnoid hemorrhage(SAH): 478, cerebral ischemia: 47, intracerebral hemorrhage(ICH): 156) who were admitted within 24 h after onset. The body temperature was measured with an electronic thermometer at the axilla on admission. The body temperatures of 73 patients with non-ruptured cerebral aneurysms on admission(admitted between 09:00 and 15:00) were used as normal control group. RESULTS: The body temperature in the control group was 36.49 +/- 0.45 degrees C. In comparison, the temperature in the SAH group was significantly lower(35.88 +/- 1.00 degrees C, n = 338, p < 0.001) when the patients were admitted within 4 h after onset, and significantly higher (36.80 +/- 0.85 degrees C, n = 140, p < 0.05) when they were admitted after 4 h and up to 24 h. There was a significant negative correlation between the severity of the SAH and body temperature within 4 h and a significant positive correlation beyond 4 h. Body temperature in the cerebral ishcemia group was significantly lower than in the control group(36.09 +/- 0.59 degrees C, n = 17, p < 0.05) when the patients were admitted within 2 h, but was close to that in the control group when they were admitted beyond 2 h and up to 24 h after onset (36.45 +/- 0.58 degrees C, n = 30). The falls of body temperature in the super-acute phase in the SAH and the cerebral ischemia groups were observed in patients admitted between 09:00 and 15:00. Although body temperature in the ICH group was slightly lower when the patients were admitted within 4 h and slightly higher when admitted beyond 4 h and up to 24 hours after onset, no significant differences were observed in comparison with the control group. In the super-acute phase of the cerebral ischemia and the ICH, body temperature tended to be lower in the patients with worse condition. CONCLUSION: This study clearly demonstrated that body temperatures in patients with CVDs changed rapidly within 24 h after onset. Body temperature in the SAH group within 4 h and that in the cerebral ischemia group within 2 h after onset was significantly lower than in the control group. These temperature falls were not the products of circadian rhythm. The temperature in the SAH group beyond 4 h and up to 24 h after onset rose significantly. Comparison with normal controls and consideration of the circadian rhythm are important when studying changes of body temperature in patients with CVDs.

Clinical background comparison of patients with and without ocular inflammatory attacks after initiation of infliximab therapy.

PURPOSE: To examine the factors affecting the efficacy of infliximab (IFX) as a treatment for uveitis in Behçet's disease. METHODS: Clinical records of 29 patients with refractory uveoretinitis were examined retrospectively for the period between 6 months before the initiation of IFX therapy to 12 months thereafter. The patients were divided into two groups based on the absence (Group 1) or occurrence (Group 2) of ocular inflammatory attacks during the observation period after IFX therapy, and the clinical records of the groups were compared RESULTS: The mean age at onset of ocular inflammation in Group 1 patients (n = 17) was lower than that in Group 2 patients (n = 12) (p = 0.023). Compared to Group 2 patients, the period from onset to IFX therapy in Group 1 was longer (p = 0.037), and the frequency of ocular inflammatory attacks before IFX therapy was lower (p = 0.013). The rates of ocular fundus attacks before IFX therapy were 0.82 ± 0.28 in Group 1 and 0.96 ± 0.10 in Group 2 (p = 0.040). Three of 33 (9.1 %) eyes in Group 1 and nine of 24 eyes (37.5 %) in Group 2 had an improved best-corrected visual acuity of >0.2 logarithm of the minimal angle resolution (p < 0.01). CONCLUSIONS: Patients in Group 1 tended to have fewer intraocular attacks (fewer fundus attacks in particular) prior to IFX therapy and have a longer period from onset of intraocular inflammation to IFX therapy. The improvement of the BCVA in Group 2 tended to be better.