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.

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.

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.

Effect of posterior vitreous detachment on aqueous humor level of vascular endothelial growth factor in exudative age-related macular degeneration patients.

BACKGROUND: To investigate the association of posterior vitreous detachment (PVD) with aqueous levels of vascular endothelial growth factor (VEGF) in eyes with exudative age-related macular degeneration (AMD). METHODS: This is a prospective comparative study. Subjects are 33 eyes with exudative AMD. PVD was examined by B-mode ultrasonography and the subjects were divided into a complete PVD group (PVD group) or a group with partial or no PVD (without PVD group). At the beginning of intravitreal injection of ranibizumab, aqueous humor was collected and the concentration of VEGF was measured using ELISA. The concentration was compared between the two groups. RESULTS: Complete PVD was observed in 13 (39 %) eyes. The mean concentration of VEGF was 58 pg/ml in the PVD group and 91 pg/ml in the without PVD group. Multiple regression analysis revealed that the concentration of VEGF was significantly lower in the eyes with PVD than in those without PVD independent of age and sex (P = 0.02). CONCLUSIONS: Complete PVD is related to the lower concentration of aqueous VEDF in AMD eyes.

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.

Clinical features of psoriatic uveitis in Japanese patients.

PURPOSE: To investigate the clinical features of psoriatic uveitis in Japanese patients. METHODS: Clinical features of 13 consecutive patients with psoriatic uveitis treated at our facility were retrospectively examined using medical records. In this study, we collected data about psoriasis type, uveitis laterality, onset type, HLA types, visual acuity, ocular inflammation localization, anterior segment findings, funduscopy findings, complications, recurrence, and medical treatments for uveitis and skin diseases. RESULTS: The cohort comprised ten males and three females (43.6 ± 7.1 years old), and types of psoriasis included psoriasis vulgaris (seven cases), psoriatic arthritis (four cases), pustular psoriasis (three cases) and psoriatic erythroderma (one case). Two cases represented complicated cases of pustular psoriasis and psoriatic arthritis. Seven cases were unilateral, and six cases were bilateral. All cases had acute non-granulomatous anterior uveitis, whereas panuveitis occurred in one case. Furthermore, macular edema and vascular leakage on fluorescein angiography occurred in four cases, and hyperemic disc occurred in two cases. Recurrence occurred in nine cases. In addition to topical corticosteroid treatment, eight cases underwent oral immunosuppressive treatment or biologics. All six cases undergoing HLA typing were HLA-A2 positive. CONCLUSIONS: Cases of psoriatic uveitis in Japan appear to present with acute non-granulomatous uveitis; other symptoms may include macular edema, retinal vasculitis, or hyperemic disc.

RELATIONSHIP BETWEEN VISUAL PROGNOSIS AND DELAY OF INTRAVITREAL INJECTION OF RANIBIZUMAB WHEN TREATING AGE-RELATED MACULAR DEGENERATION.

BACKGROUND: In age-related macular degeneration, various factors in clinical practice cause delays to arise between the time exudative change is observed and the time anti-vascular endothelial growth factor drugs are actually injected. We investigated the influence of injection delay on prognosis. METHODS: Subjects were 50 eyes (50 patients from 2 hospitals) that were administered ranibizumab monotherapy for age-related macular degeneration for 1 year since exudative change was first observed. We investigated the mean number of delay days for each injection. RESULTS: Mean injection delay was between 0 and 104 days. Significant prognostic factors for visual acuity were initial best-corrected visual acuity (P < 0.01) and mean injection delay (P = 0.03). We estimated that for an initial best-corrected visual acuity of 0.40 logMAR unit (20/50 Snellen equivalent), the respective best-corrected visual acuity values after 1 year for mean injection delays of 0, 7, 14, 28, and 56 days would be 0.22 (20/33), 0.24 (20/35), 0.26 (20/37), 0.31 (20/40), and 0.39 (20/49). For an initial best-corrected visual acuity of 0.097 (20/25), the respective values would be 0.054 (20/23), 0.075 (20/24), 0.10 (20/25), 0.14 (20/28), and 0.22 (20/33). CONCLUSION: Long-term visual acuity prognosis worsened when scheduling problems delayed intravitreal injection of anti-vascular endothelial growth factor drugs.

Occult macular dystrophy with bilateral chronic subfoveal serous retinal detachment associated with a novel RP1L1 mutation (p.S1199P).

PURPOSE: The purpose of this study was to present an atypical case of occult macular dystrophy (OMD) with bilateral chronic subfoveal serous retinal detachment (SRD). METHODS: A 53-year-old man was ophthalmologically evaluated because of decreased visual acuity in both eyes. Genomic DNA was extracted from venous blood samples. Mutational analysis of the retinitis pigmentosa 1-like 1 (RP1L1) gene was performed by Sanger sequencing. RESULTS: Best-corrected visual acuity (BCVA) was 0.1 logMAR in both eyes until the age of 53, after which it gradually declined. Full-field electroretinography (ERG) was unremarkable, while multifocal ERG revealed a reduced central response in both eyes. Optical coherence tomography showed subfoveal SRD in both eyes, and fundus fluorescein angiography yielded unremarkable results. His brother and cousin had similar subjective symptoms. At age 58, his logMAR BCVA was 0.532 (OD) and 0.347 (OS). He was given 23 administrations of intravitreal bevacizumab (IVB; 1.25 mg) in both eyes alternately over a 2-year period and also underwent reduced-fluence photodynamic therapy in both eyes. Two years after the first administration of IVB, a reduction in SRD was obtained, and IVB was therefore discontinued. Three years after the first administration, logMAR BCVA was 0.155 (OD) and 0.523 (OS). Mutational analysis revealed a novel heterozygous missense mutation (p.S1199P). CONCLUSIONS: We describe in detail a case of bilateral chronic subfoveal SRD in an atypical OMD patient carrying a novel heterozygous RP1L1 mutation (p.S1199P). Our results further extend the phenotypic spectrum of RP1L1-associated OMD.

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.

Effects of Japanese herbal medicine Sairei-to on murine experimental autoimmune uveitis.

PURPOSE: It has been suggested thatSairei-to (TJ114), a traditional Japanese herbal medicine, has immunomodulatory activities. To evaluate the effects of TJ114 on uveitis, we examined the effectiveness of oral administration in a murine model of experimental autoimmune uveitis (EAU). METHODS: Murine EAU was induced by subcutaneous injection of human inter-photoreceptor retinoid-binding protein (IRBP) peptide mixed with complete Freund's adjuvant. In the TJ114-treated group, 2 g/kg was administrated orally from 0 to 20 days after immunization. Clinical scoring, histopathological scoring of EAU, cell proliferation, cytokine assessment, and adoptive transfer experiment of splenic T cells into naïve mice were performed. RESULTS: EAU development occurred in 32 of 38 mice (86 %) in the untreated group and 12 of 33 (36 %) in the TJ114-treated group. The clinical scores for EAU in the vehicle-treated and TJ114-treated groups were 1.56 ± 1.65 and 0.59 ± 0.63 respectively, at 14 days after immunization (p < 0.01, Mann-Whitney U-test), and 2.26 ± 1.56 and 0.75 ± 1.31 respectively at 21 days (p < 0.001, Mann-Whitney U-test), while the histopathological scores at 21 days were 1.47 ± 1.42 and 0.54 ± 0.84 respectively (p < 0.01, Mann-Whitney U-test). Interferon (IFN)-γ and tumor necrosis factor (TNF)-α production by cervical lymph node cells obtained from the TJ114-treated group were significantly reduced as compared with those from the vehicle-treated group (p < 0.01, Student's unpaired t-test). Moreover, the levels of C-C motif chemokine 2 (CCL2) and IFN-γ were significantly reduced in splenocytes of TJ114-treated mice as compared with the vehicle-treated group (p < 0.01, Student's unpaired t-test). Mice that received adoptive transfer of splenic T cells from TJ114-treated EAU mice caused significantly lower severity of EAU compared to those that received from vehicle-treated EAU mice. CONCLUSION: Oral administration of TJ114 has an inhibitory effect on a murine model of EAU, possibly via reduction in cytokine production by helper type-1 T cells.

Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia.

Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/µl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/µl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.

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.

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.

Endogenous Candida albicans infection causing subretinal abscess.

PURPOSE: We report a case of Candida albicans endophthalmitis with subretinal abscess formation in a patient who underwent liver transplantation. METHODS: Case report. RESULTS: A 51-year-old Japanese woman complained of deep pain and ciliary injection in her right eye. Three months prior, the patient had undergone liver transplantation for cirrhosis caused by hepatitis C. A slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and fundoscopy showed a yellowish-white subretinal mass lesion in the inferior peripheral fundus. Systemic and topical antibiotics did not prevent further progression of the infection. The patient underwent pars plana vitrectomy treatment three times and a histopathological study of a vitreous specimen revealed C. albicans to be the causative organism. CONCLUSION: A subretinal abscess, previously reported in Nocardia, Pseudomonas, Staphylococcus, and Aspergillus infection cases, can also occur in patients infected with Candida. Therefore, Candida infection should be considered as a potential cause of subretinal abscess in organ transplant recipients.

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.

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.

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.

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.

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.

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.