Factors Associated With Intraocular Inflammation in Neovascular Age-Related Macular Degeneration Patients Treated With Brolucizumab.

Purpose: To identify factors associated with intraocular inflammation (IOI) in patients with neovascular age-related macular degeneration (nAMD) treated with brolucizumab. Methods: In this prospective observational study, we collected aqueous humor samples from 96 eyes of 96 patients receiving treatment with brolucizumab; IOI subsequently developed in 19 eyes of 19 patients. To identify cytokines upregulated in eyes with subsequent development of IOI, we compared the aqueous humor cytokine levels between the IOI and non-IOI groups. We also collected plasma from 20 patients who developed IOI and 20 age- and sex-matched controls to identify differences in plasma biomarkers and the subfraction of CD4+ cells. Using stepwise variable selection and multivariate binary regression analysis, we developed an algorithm that accurately assessed the likelihood of IOI occurrence. Results: The IOI group showed elevated aqueous humor levels of P-selectin (584 vs. 324 pg/mL, P = 0.013), TNF-α (0.89 vs. 0.60 pg/mL, P = 0.018), and IL-1α (2.0 vs. 1.4 pg/mL, P = 0.035) compared with the non-IOI group. Serum MMP-9 concentrations were higher in the IOI group than the non-IOI group (18,310 vs. 13,450 pg/mL, P = 0.029). Furthermore, the percentage of Th2 cells was significantly decreased in the IOI compared with the non-IOI group (3.1% vs. 4.2%, P = 0.013). The receiver operating characteristic curves for the optimal models showed an area under the curve ranging from 0.71 to 0.89, indicating good performance. Conclusions: The combination of elevated concentrations of multiple aqueous humor cytokines and of serum MMP-9 and a lower number of plasma Th2 cells is associated with brolucizumab-related IOI in patients with nAMD.

Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.

Aqueous humour proteins and treatment outcomes of anti-VEGF therapy in neovascular age-related macular degeneration.

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (ß coefficient = -0.088, P = 0.040) and central retinal thickness (ß coefficient = 0.00051 per µm, P = 0.027), MCP-1 (ß coefficient = 0.44, P < 0.001) and IL-10 (ß coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (ß coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (ß coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (ß coefficient = 0.56, P = 0.01), CXCL12 at the third injection (ß coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (ß coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.

Comparisons of Clinical Features in Japanese Patients with Behçet's Uveitis Treated in the 1990s and the 2000s.

Purpose: We investigated clinical characteristics of ocular Behçet's disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24-6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.

Comparison of visual field defect progression in secondary Glaucoma due to anterior uveitis caused by three types of herpes viruses.

PURPOSE: To clarify the prevalence of secondary glaucoma (SG) and its speed of progression in patients with herpes simplex virus (HSV)-anterior uveitis (AU), varicella zoster virus (VZV)-AU, and cytomegalovirus (CMV)-AU. METHODS: In total, 170 patients with herpetic AU were enrolled in this retrospective observational case series. Patients with visual field (VF) defects and glaucomatous disc abnormalities were diagnosed with SG. Moreover, the speed of SG progression was defined as decreasing mean deviation (MD) values per year. SG prevalence and annual MD-value decrease were compared among the three types of herpetic AU. RESULTS: SG prevalence was 16%, 9%, and 72% in patients with HSV-AU, VZV-AU, and CMV-AU, respectively. Patients with CMV-AU had the highest SG prevalence (odds ratio = 3.15; 95% confidence interval = 1.15-8.65; P < 0.05). Furthermore, the annual MD-value change was significantly higher in SG caused by CMV-AU than in that caused by HSV/VZV-AU (-2.6 ± 2.4 dB/year and -0.45 ± 0.54 dB/year, respectively; P < 0.05). CONCLUSIONS: Our results demonstrated that patients with CMV-AU may have a higher risk and faster speed of progression of SG than patients with HSV/VZV-AU. Therefore, clinicians should monitor glaucoma onset and VF-defect progression in patients with CMV-AU.

Association between subfoveal choroidal thickness and leakage site on fluorescein angiography in Behçet's uveitis.

This study aimed to clarify the association between the retinal leakage site on fluorescein angiography (FA) and subfoveal choroidal thickness (SCT) measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Twenty-two patients with Behçet's uveitis were retrospectively selected in this study. They underwent EDI-OCT and FA in both the active and convalescent phases. The associations of the changes between the active and convalescent phases in SCT and in FA leakage in various retinal areas (total retina, peripheral retina, macula, and optic disc) were examined. The changing rates of SCT between the two investigated phases were significantly associated with the changes in total FA leakage scores (y = 1.79X+ 11.7, r2 = 0.210, p < 0.05). Furthermore, the changes in FA leakage scores in the macula were correlated with the changing rates in SCT (y = 3.72X+ 13.9, r2 = 0.219, p < 0.05). By contrast, there were no significant associations between the changes in SCT and those in leakage from the peripheral retina or the optic disc on FA. These findings demonstrate that SCT may reflect macular vasculitis as determined using FA, and SCT measurement could be a non-invasive method to investigate inflammation near the macula in Behçet's uveitis.

Epidemiology of uveitis (2013-2015) and changes in the patterns of uveitis (2004-2015) in the central Tokyo area: a retrospective study.

BACKGROUND: The distribution of uveitis varies with genetic, ethnic, geographic, environmental, and lifestyle factors. Epidemiological information about the patterns of uveitis is useful when an ophthalmologist considers the diagnosis of uveitis. Therefore, it is important to identify the causes of uveitis over the years in different regions. The purposes of this study were to characterize the uveitis patients who first arrived at the University of Tokyo Hospital in 2013-2015, and to analyze the changes in the patterns of uveitis from 2004 to 2012 to 2013-2015. METHODS: We retrospectively identified 750 newly arrived patients with uveitis who visited the Uveitis Clinic in the University of Tokyo Hospital between January 2013 and December 2015, using clinical records. We extracted data on patient age, sex, diagnosis, anatomic location of inflammation, laboratory test results of blood and urine, and chest X-ray and fluorescein fundus angiography findings for each patient. In addition, we compared these data with those from 2004 to 2012 to analyze the changes in the patterns of uveitis. RESULTS: A definite diagnosis was established in 445 patients (59.3%). The most common diagnoses were herpetic iridocyclitis (7.5%), sarcoidosis (6.1%), Behçet's disease (4.4%), Vogt-Koyanagi-Harada disease (4.1%), and intraocular lymphoma (4.1%). The most frequent unclassified type of uveitis was suspected sarcoidosis (22.3%). Analysis of the changes in the patterns of uveitis in the central Tokyo area from 2004 to 2012 to 2013-2015 revealed notable increasing trends of herpetic iridocyclitis and intraocular lymphoma, and increasing trends of bacterial endophthalmitis, fungal endophthalmitis, and juvenile chronic iridocyclitis. In contrast, the frequency of sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada disease decreased. CONCLUSIONS: The patterns of uveitis changed considerably from 2004 to 2012 to 2013-2015. Continuous investigations about the epidemiology of uveitis are needed to diagnose uveitis more accurately.

Intravitreal aflibercept for exudative age-related macular degeneration with good visual acuity: 2-year results of a prospective study.

PURPOSE: We report the 2-year outcomes of intravitreal aflibercept (IVA) for exudative age-related macular degeneration (AMD) with good visual acuity (VA) and examine the baseline factors associated with good visual outcome. MATERIALS AND METHODS: This multicenter, prospective study evaluated 39 eyes (39 AMD patients) enrolled from August 2013 to August 2014 at 12 and 24 months. Only patients with initial best-corrected VA (BCVA) >0.3 logarithm of the minimum angle of resolution (20/40 Snellen) were eligible. Three consecutive monthly IVA injections were followed by 2 monthly injections for 12 months. Thereafter, patients received injections on a treat- and-extend regimen for up to 24 months. Outcome measures included BCVA and central macular thickness (CMT) at 12 and 24 months. Post hoc analysis, BCVA, and CMT were evaluated by AMD types (typical AMD [tAMD], type 1, and type 2 polypoidal choroidal vasculopathy [PCV]). Baseline characteristics and BCVA associations were evaluated with linear regression analysis and Student's t-test. RESULTS: Mean age was 69 years and 26 of 39 eyes were male. tAMD, type 1 and type 2 PCV occurred in 18, 12, and 9 eyes, respectively. Baseline mean BCVA was 0.097 logarithm of the minimum angle of resolution (20/25 Snellen) and showed significant improvement to 0.058 (20/22 Snellen, P=0.03) at 12 months and 0.066 (20/23) at 24 months. CMT improved significantly from 320 (99) µm (mean [SD]) to 250 (93) µm (P=0.002) at 12 months and 240 (93) µm (P=0.0005) at 24 months. BCVA and CMT were not significantly different among the three groups. Only subretinal hemorrhage (SRH) was significantly associated with improved BCVA. BCVA change from baseline was -0.12 with SRH and -0.011 without SRH (P=0.017) at 12 months. CONCLUSION: IVA showed good efficacy for exudative AMD with good VA at 24 months. tAMD and type 1 and 2 PCV showed similar prognosis. Baseline SRH predicted favorable long-term vision in AMD with good VA.

Clinical characteristics and ocular complications of patients with scleritis in Japanese.

PURPOSE: To investigate the clinical characteristics of Japanese patients with scleritis STUDY DESIGN: Retrospective study METHODS: The clinical records of 123 patients with scleritis, who presented to the University of Tokyo Hospital between January, 2004 and December, 2015, were retrospectively reviewed. RESULTS: The cohort comprised 55 men and 68 women (mean age, 57.8±16.4 years), of which 76 showed anterior diffuse scleritis, 17 showed anterior nodular scleritis, 10 showed anterior necrotizing scleritis, and 20 showed posterior scleritis. The underlying etiology was identified in 39 patients. Autoimmune diseases were present in 32 patients, including eight with rheumatoid arthritis, seven with antineutrophil cytoplasmic antibody-associated vascular disease, and six with relapsing polychondritis. Ocular hypertension was the most common ocular complication (41%), followed by anterior chamber cells (38%). Fifty-three percent of patients required systemic immunosuppressive medication. Systemic corticosteroids were the most commonly used medication (45%), followed by methotrexate (11%). A, decrease in vision was observed in one-third of patients with anterior necrotizing scleritis or posterior scleritis, of which secondary glaucoma and optic neuritis were the major causes. CONCLUSION: Autoimmune diseases were present in 26% of patients. One-third of patients with anterior necrotizing scleritis or posterior scleritis experienced decreased vision, mostly due to secondary glaucoma and optic neuritis. Therefore, controlling intraocular pressure by methods such as administration of steroid-sparing immunosuppressive medication and appropriate treatment for posterior scleritis are essential for scleritis treatment.

NOVEL PRERETINAL HAIR PIN-LIKE VESSEL IN RETINAL ASTROCYTIC HAMARTOMA WITH VITREOUS HEMORRHAGE.

BACKGROUD/PURPOSE: To report a case of retinal astrocytic hamartoma with vitreous hemorrhage and a hair pin-like vessel adhering to a posterior vitreous membrane. A 33-year-old man with a retinal astrocytic hamartoma presented with vitreous hemorrhage 5 times. METHODS: Multimodal imaging, including fundus photography, fluorescein angiography, optical coherence tomography, and B-mode ultrasonography. RESULTS: Multimodal imaging demonstrated a novel hair pin-like vessel that adhered to the posterior vitreous membrane. CONCLUSION: Some cases of retinal astrocytic hamartoma with vitreous hemorrhage may be related to structure abnormalities of tumor vessels.

Visual acuity loss associated with excessive "dry macula" in exudative age-related macular degeneration.

PURPOSE: To investigate the correlation between visual acuity and central macular thickness (CMT) and choroidal thickness (CCT) in patients with wet age-related macular degeneration (AMD). METHODS: In this retrospective analysis, 14 eyes that received >10 ranibizumab injections (based on pro re nata [PRN] regimen) and maintained initial visual acuity gain were analyzed. The following 5 parameters were measured at the foveal center: CMT (distance from the inner limiting membrane [ILM] to Bruch's membrane); central retinal thickness (CRT; distance from the ILM to the inner limit of the retinal pigment epithelium or subretinal fluid [SRF]); SRF thickness (SRFT); pigment epithelium detachment thickness (PEDT); and CCT. The correlation between the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and the 5 parameters was examined with generalized estimating equations. RESULTS: CMT, CRT, and CCT were negatively correlated with logMAR BCVA (P=0.031, 0.023, and 0.036, respectively) when only CMT values less than the thickness that maximized visual acuity for each eye were used for the analysis. Each 100-µm reduction in CMT, CRT, or CCT improved logMAR BCVA by -0.1, -0.08, or -0.07, respectively. SRFT and PEDT were not correlated with BCVA. The median CMT that maximized the visual acuity was 230 µm. CONCLUSION: Dry macula with CMT <230 µm was associated with temporary decrease in visual acuity in AMD patients whose visual acuity was maintained with PRN regimen.

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.

Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy.

PURPOSE: To determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD). METHODS: This prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and third (2 months later) injections. Controls were 80 eyes with cataracts without retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon-γ-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1), CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin-10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex cytokine assays. RESULTS: Mean ages of the patients with AMD and controls were 73 and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men, respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean concentrations of cytokines in aqueous humour in patients with neovascular AMD before the first and third ranibizumab injections were as follows (in pg/mL): CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6; MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015 (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations of all cytokines decreased significantly after two consecutive ranibizumab injections, except for MMP-9, which increased significantly. CONCLUSIONS: After two monthly consecutive antivascular endothelial growth factor injections, inflammatory cytokine levels in the aqueous humour of the eyes with AMD were strongly suppressed, while MMP-9 levels increased.

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.

Effective Intravitreal Injections of Bevacizumab in a Case of Serous Macular Detachment from the Superior Border of the Posterior Staphyloma.

PURPOSE: We present an atypical case of submacular fluid leading to serous macular detachment. METHOD/PATIENT: A 69-year-old man was evaluated for metamorphopsia in the left eye. RESULTS: Best-corrected visual acuity was 20/25 in both eyes. He had undergone cataract surgeries in both eyes 12 years ago. The axial length was 25.93 mm (OD) and 24.12 mm (OS). Optical coherence tomography showed posterior staphylomas and subretinal fluid on the superior border of the staphylomas in both eyes; in the left eye, submacular fluid was noted extending up to the macula. Fundus fluorescein angiography revealed leakage from the superior border of the staphylomas in both eyes. The fluid persisted for 4 months. Four consecutive, monthly injections of bevacizumab (1.25 mg/0.05 mL) were administered in the left eye; subsequently, the subretinal fluid gradually dissipated from the macula and became localized at the superior border of the staphyloma. This localization persisted for 12 months. CONCLUSIONS: We have detailed a case of submacular fluid that spread from the superior border of the posterior staphyloma in a patient with macular detachment, in whom intravitreal injections of bevacizumab were highly effective in eliminating the fluid.

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.

Vascular Endothelial Growth Factor (VEGF) Concentration Is Underestimated by Enzyme-Linked Immunosorbent Assay in the Presence of Anti-VEGF Drugs.

PURPOSE: Commercially available enzyme-linked immunosorbent assay (ELISA) kits are often used to monitor vascular endothelial growth factor (VEGF) levels in exudative age-related macular degeneration. To test their accuracy, this study performed measurements using the ELISA kits in the presence of anti-VEGF drugs. METHODS: The concentrations of bevacizumab, pegaptanib, or ranibizumab at 28 days and aflibercept at 28 and 56 days after an injection were estimated based on previous pharmacokinetic studies. Vascular endothelial growth factor concentrations were measured with two widely used VEGF ELISA kits in the presence of anti-VEGF drugs or control mouse immunoglobulin G (IgG). The monocyte chemotactic protein-1 (MCP-1) ELISA kit was used as a non-VEGF ELISA control kit. RESULTS: The concentrations of aflibercept, bevacizumab, pegaptanib, and ranibizumab were estimated at 0.14 to 7.2, 4.9, 8.6, and 0.11 to 1.1 µg/mL, respectively. ELISA underestimated the VEGF concentration 2- to 100-fold lower in the presence of an anti-VEGF drug, except for pegaptanib, at all VEGF concentrations tested (7.8-1500 pg/mL). Vascular endothelial growth factor at 1000 pg/mL was measured as 92, 150, and 170 pg/mL in the presence of aflibercept (7.2 µg/mL), bevacizumab (4.9 µg/mL), and ranibizumab (1.1 µg/mL), respectively (all P < 0.0001), and the measured VEGF concentration decreased proportionately by 90% to 92% with aflibercept, 85% to 94% with bevacizumab, and 83% to 99% with ranibizumab. The control mouse IgG did not interfere with the measurement of VEGF. Ranibizumab did not affect the measurements with MCP-1 ELISA. CONCLUSIONS: Investigators should exercise caution when interpreting measurements of VEGF ELISA in patients being treated with an anti-VEGF drug.

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.

ASSOCIATION BETWEEN AQUEOUS HUMOR CXC MOTIF CHEMOKINE LIGAND 13 LEVELS AND SUBFOVEAL CHOROIDAL THICKNESS IN NORMAL OLDER SUBJECTS.

PURPOSE: To investigate the association of subfoveal choroidal thickness with intraocular inflammatory cytokines and chemokines. METHODS: The subjects consisted of 76 eyes of consecutive cataract patients at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between September 2010 and August 2012. In addition, two autopsy eyes from elderly males were used for immunohistochemical study. Subfoveal choroidal thickness was measured using spectral domain optical coherence tomography before cataract surgery. At the beginning of cataract surgery, a sample of undiluted aqueous humor was manually aspirated and the concentrations of the following cytokines were determined using a multiplex cytokine assay: IP-10, MCP-1, MMP-9, IL-6, IL-10, CXCL1, CXCL12, CXCL13, and CCL11. The association of subfoveal choroidal thickness with intraocular cytokine concentration was analyzed. Expression of CXCL13 was examined in autopsy eyes. RESULTS: Among these factors, higher concentration of CXCL13 was associated with thicker choroid. In particular, multiple regression analysis showed that the concentration of CXCL13 was associated with subfoveal choroidal thickness (P = 0.001), independently of axial length (P = 0.049). By immunostaining, CXCL13 was clearly detected in choroidal endothelial cells. CONCLUSION: Aqueous humor concentration of CXCL13 is correlated with subfoveal choroidal thickness in normal subjects.