A Systematic Review and Meta-Analysis of Clinical Outcomes of Small Gauge Vitrectomy with or without Intravitreal Anti-Vascular Endothelial Growth Factor Agents Pretreatment for Proliferative Diabetic Retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a common visual threatening ocular disease, patients with nonclearing vitreous hemorrhage (VH), tractional retinal detachment (RD), or extensive fibrovascular proliferation are always in need for surgical treatment. Although several studies reported better surgical outcome in patients underwent surgery after anti-VEGF injection, the effect of anti-VEGF pretreatment for small gauge vitrectomy in PDR patients remains to be elucidated. OBJECTIVES: The objective of the study was to evaluate the benefits of preoperative anti-VEGF treatment in small gauge vitrectomy for PDR patients. METHODS: A comprehensive literature search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify relevant studies. Meta-analyses were performed for intraoperative (including intraoperative bleeding, endodiathermy, iatrogenic retinal breaks, surgical time, etc.) and postoperative outcome parameters (including best-corrected visual acuity (BCVA), postoperative VH, postoperative RD, etc.). RESULTS: Ten randomized controlled trials were identified and used for comparing small gauge vitrectomy alone (344 eyes, control group) and small gauge vitrectomy with preoperative anti-VEGF injection (355 eyes). The intraoperative findings showed that the surgical time, the incidence of clinically significant intraoperative bleeding, iatrogenic retinal breaks, silicone oil tamponade, and the frequency of endodiathermy were significantly less in the anti-VEGF pre-treated group than in the vitrectomy alone group (p < 0.01). The postoperative findings showed that the incidences of early postoperative VH, postoperative RD were significantly less in the anti-VEGF pre-treated group than in the control group (p < 0.05). The pooled result of postoperative rubeosis iridis/neovascular glaucoma was borderline (p = 0.072) between cases and controls, while no statistically significant differences in BCVA at last follow-up and incidences of late postoperative VH were found between these two groups (p > 0.05). CONCLUSIONS: Anti-VEGF injection prior to small gauge vitrectomy in PDR patients might facilitate easier surgical procedure and reduce intra- and postoperative complications. Further studies are needed to verify our findings and evaluate the optimal interval and dosage for preoperative anti-VEGF injection.

TRPM4 and TRPV2 are two novel prognostic biomarkers and promising targeted therapy in UVM.

Uveal melanoma (UVM) is the most common primary intraocular malignancy tumor in adults. Almost 50% of UVM patients develop metastatic disease, and is usually fatal within 1 year. However, the mechanism of etiology remains unclear. The lack of prognostic, diagnostic and therapeutic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play important roles in the occurrence and development of tumors, which may have the potential as a therapeutic target for UVM. This current study aimed to identify the potential effect and function of the TRPs that could provide survival prediction and new insight into therapy for UVM. Based on the transcriptome data and potential key genes of UVM were screened using the Cancer Genome Atlas (TCGA) databases, Gene expression analysis showed the expression of TRPM4, TRPV2 and other TRPs was high levels in UVM. Using survival analysis, we screened out that the high expression of TRPM4 and TRPV2 was negatively correlated with the prognosis of UVM patients. Cox regression analysis and functional enrichment analysis further indicated that TRPM4 and TRPV2 were the most convincing therapeutic targets of UVM, and the majority of genes involved in ferroptosis pathways in UVM showed positively correlated with the expression levels of TRPM4 and TRPV2. In conclusion, TRPM4 and TRPV2 were considered as two novel prognostic biomarkers and a promising targeted therapy in UVM.

Anterior Segment Inflammation in Pediatric Uveitis Is Associated with Reduced Retinal Vascular Density as Quantified by Optical Coherence Tomography Angiography.

PURPOSE: To analyze the retinal capillary vascular density (VD) as quantified by optical coherence tomography angiography (OCTA) in patients with pediatric uveitis. METHODS: OCTA images of 32 pediatric uveitis patients and 30 normal controls (NC) were obtained retrospectively. The foveal avascular zone (FAZ) area, VDs in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) were analyzed and compared between active and quiescent uveitic eyes, contralateral eyes and NC eyes. RESULTS: Compared with NCs, the VDs in the SCP and DCP were significantly reduced in eyes with both active and quiescent pediatric uveitis (P < .05).The SFCT was increased significantly in the active group relative to the quiescent group and NC groups (P < .05). In contrast, no significant differences were observed in the FAZ and CMT (all P > .05). CONCLUSIONS: Our quantitative OCTA findings suggest that the posterior segment is affected during anterior segment recurrence in patients with pediatric uveitis.

A single nucleotide polymorphism in the IL1RL1 gene is associated with Behcet's disease in a Chinese Han population.

AIM: To explore the association of single nucleotide polymorphisms (SNPs) in the IL33/IL1RL1 gene region with the susceptibility to Behcet's disease (BD) in a Chinese Han population. METHODS: A total of eight SNPs in the candidate gene region (rs11792633, rs7025417, rs10975519 and rs1048274 in IL33; rs2310220, rs12712142, rs13424006 and rs3821204 in IL1RL1) were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array iPLEX platform. RESULTS: A statistically significant association was observed between IL1RL1 rs12712142 and BD patients. The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls (OR=0.8, 95%CI: 0.69-0.94, Pc=0.039); the genotype distribution (Pc=0.043) and additive and dominant genetic model analyses (OR=0.8, 95%CI: 0.69-0.94, Pc=0.040 and OR=0.72, 95%CI: 0.58-0.88, Pc=0.011) also indicated a strong association between rs12712142 and BD patients. CONCLUSION: This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population, indicating a protective role of IL1RL1 in the pathogenesis of BD.

Comparison of the Safety and Efficacy of Interferon Alpha-2a and Cyclosporine-A When Combined With Glucocorticoid in the Treatment of Refractory Behçet's Uveitis: A Randomized Controlled Prospective Study.

Purpose: To evaluate and compare the efficacy and safety of interferon alpha-2a (IFN-α2a) and cyclosporine-A (CsA) in patients with refractory Behçet's uveitis (BU). Methods: In this 12-month randomized, controlled, prospective trial, 26 participants (44 eyes) completed the study. Patients were randomly allocated to the IFN-α2a or CsA groups. All patients in both groups received a standardized prednisone burst and tapering schedule as per protocol. The primary outcome measures were response rate, complete remission rate, and tolerance rate. The secondary outcome measures included time to achieve complete remission, the logarithm of the minimum angle of resolution (logMAR) of best-corrected visual acuity (BCVA), and Behçet's disease ocular attack score 24 (BOS24). T-tests and non-parametric tests were used to compare quantitative variables, and chi-square tests were performed to compare qualitative variables. Results: The response and complete remission rates were 85.7% (12/14 patients) and 50.0% (7/14 patients) in the IFN-α2a group, compared with 66.7% (8/12 patients) and 25.0% (3/12 patients) in the CsA group, respectively (p > 0.05). Complete remission was achieved at 3.3 and 7.0 months after initiation of IFN-α2a and CsA (p = 0.023). LogMAR BCVA significantly improved 1 month after IFN-α2a initiation (23 eyes) (p = 0.002), and this beneficial effect remained statistically significant during the entire follow-up period (p < 0.05); however, this improvement was not observed in the CsA group (21 eyes). At the endpoint, LogMAR BCVA in the IFN-α2a group was significantly better (0.22 vs. 0.31, p = 0.031) with a higher improvement rate (60.9 vs. 47.6%, p > 0.05). Moreover, compared to the CsA group, more eyes in the IFN-α2a group had a lower BOS24 score (87.0 vs. 57.1%, p = 0.042). None of the patients had any side effects that influenced the medication adherence. Conclusion: Compared to CsA plus corticosteroid, IFN-α2a plus corticosteroid appears to induce a better treatment response, a significantly greater improvement in visual acuity, and more stable remission of intraocular inflammation in a 12-month study period.

Decrease of choriocapillary vascular density measured by optical coherence tomography angiography in Vogt-Koyanagi-Harada disease.

PURPOSE: Changes of choroidal circulation throughout the disease course of Vogt-Koyanagi-Harada (VKH) disease and the clinical significance remain unclear. Choriocapillary vascular density (CC VD) measured by optical coherence tomography angiography (OCTA) were compared in different disease stages of VKH and its correlation with other parameters was analyzed, aiming to explore their clinical relevance. METHODS: This is a retrospective case series. One hundred and fourteen VKH patients and 47 normal controls (NCs) were included. Patients were grouped into the acute uveitic, convalescent, and chronic recurrent stages (only anterior recurrent cases included), and OCTA images were obtained from VKH patients in these stages. Best corrected visual acuity (BCVA), CC VD, and subfoveal choroidal thickness (SFCT) were recorded and compared. RESULTS: CC VD in acute (58.26% ± 0.84%), convalescent (64.85% ± 0.33%), and chronic recurrent (62.78% ± 0.70%) stage of VKH patients were all significantly lower than that in NCs (66.37% ± 0.41%) (p < 0.001, p = 0.017, and p < 0.001, respectively). CC VD increased by 6.59% ± 0.91% with resolution of acute inflammation (p < 0.001) and decreased by 2.07% ± 0.74% during anterior uveitis relapse (p = 0.009). Patients with a positive history of anterior recurrence had lower CC VD (- 2.43% ± 0.75%, p = 0.003) in the convalescent stage than those without. CC VD was negatively correlated with logMAR BCVA in VKH (r = - 0.261, p < 0.001). CONCLUSION: CC VD was decreased in every stage of VKH. CC VD has the potential to reflect the status of uveitis and might be promising in monitoring the disease activity. OCTA is a convenient and straightforward tool to evaluate choroidal vascularity, and CC VD provides supplemental quantitative information of the choriocapillaris. Further studies are needed to explore the values of OCTA quantitative parameters in monitoring VKH progression, predicting visual prognosis, and guiding clinical decisions.

Genetic Association of Interleukin 33/ST2 Polymorphisms With Behcet's Uveitis.

Interleukin (IL)33, a member of the IL1 superfamily, functions as a nuclear factor and mediates biological effects by interacting with the ST2 receptor. Recent studies have described IL33 as an emerging pro-inflammatory cytokine in the immune system, and IL33/ST2 gene polymorphisms have been implicated in the pathogenesis of various immune diseases. However, the underlying mechanisms of IL33/ST2 in Behcet's disease (BD) remain to be defined. Here, we investigated the association between IL33/ST2 gene polymorphisms and BD in 585 BD uveitis (BDU) patients and 834 healthy controls using Agena MassARRAY iPLEX platform. We found that rs3821204 was associated with the development of BDU. Moreover, the frequency of rs2210463 G allele was lower in patients with genital involvement. Association analysis revealed a much greater genetic difference between complete-type and incomplete-type BD groups, including three SNPs (rs7044343, rs1048274, and rs2210463). Our findings suggest that IL33/ST2 gene polymorphisms are involved in the pathogenesis of BDU. Different genetic backgrounds may exist in complete-type and incomplete-type BD patients.

Retinal Microcirculation Defects on OCTA Correlate with Active Inflammation and Vision in Vogt-Koyanagi-Harada Disease.

Purpose: To analyze quantitative OCT-angiography (OCTA) measurements of Vogt-Koyanagi-Harada (VKH) disease at different disease stages.Methods: OCTA scans of 110 VKH patients in acute uveitic, convalescent and chronic recurrent stage were reviewed; posterior uveitis recurrent cases were excluded. Superficial and deep capillary plexus (SCP and DCP) vascular densities (VD) and subfoveal choroidal thickness (SFCT) were compared.Results: DCP VD was significantly lower and SFCT higher in VKH than normal controls (NC) in all 3 stages (all p < .001). Anterior uveitis recurrent patients had lower SCP and DCP VDs and thicker SFCT than convalescent patients (p = .001, p < .001, and p = .003, respectively). DCP VD was significantly correlated with visual acuity (p < .05). Patients with history of anterior recurrence had lower retinal VDs in the convalescent stage than those without (p < .001).Conclusion: Retinal microcirculation is impaired in VKH. DCP VD might be a sensitive indicator of inflammatory status and appeared to be well associated with visual outcome.

Analysis of Parafoveal Microvascular Abnormalities in Behcet's Uveitis Using Projection-Resolved Optical Coherence Tomographic Angiography.

Purpose: To assess the characteristics of parafoveal microvascular abnormalities in Behcet's uveitis (BDU) using projection-resolved optical coherence tomographic angiography (PR-OCTA).Methods: A retrospective study of BDU patients who underwent PR-OCTA examination between April 1, 2017 and October 31, 2018.Results: Sixty consecutive BDU patients (102 eyes) were included. Sixty-two (124 eyes) healthy subjects served as normal controls (NCs). As compared with NCs, the vessel densities (VDs) of superficial and deep retinal capillary plexuses were decreased, and the fovea avascular zone area, perimeter and acircularity index were increased in BDU eyes (all p < .001). Macular edema (p < .001) and long uveitis course (p = .033) were identified as risk factors for capillary disruptions. Consistent VD reductions were observed in the quiescent fellow eyes of BDU patients during unilateral uveitis relapse.Conclusions: BDU patients had significant OCTA changes. Macular circulatory disturbances may exist in the quiescent fellow eyes during unilateral BDU attack.

Bilateral mantle cell lymphoma of the ciliary body that responded to a combined local radiotherapy and chemotherapy regimen: a case report.

BACKGROUND: Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) that often affects men over the age of 60. Systemic metastasis of MCL to eyes is rare and intraocular involvement is even rarer, which usually affects the choroid and iris. To the best of our knowledge, ciliary body metastasis of systemic MCL has not been reported. CASE PRESENTATION: A 59-year-old Han Chinese male with past-history of systemic MCL complained of redness, pain and blurred vision in the left eye. Ocular examination revealed a normal appearance in the right eye, and conjunctival injection, pseudohypopyon and anterior protrusion of peripheral iris in the left eye, all of which were unresponsive to corticosteroid treatments. Ultrasound biomicroscopy (UBM) and B-scan were then performed which detected ciliary body masses in both eyes with no vitreous and retino-choroidal anomalies. Combined liquid-based cytology tests and gene rearrangement assays of the aqueous humor specimen confirmed this to be a B-cell malignancy. Then both eyes were treated with external beam irradiation (40 Gy, delivered evenly in twenty fractions) over a course of one month. Additionally, the left eye received intravitreal methotrexate (MTX) (weekly for the first month, every two weeks for the second month, and monthly thereafter) over a course of twelve months. This therapy eventually led to complete remission of all symptoms in one month and disappearance of the ciliary body masses in twelve months. CONCLUSION: Here we first reported a case of bilateral ciliary body MCL infiltration which was diagnosed by combined liguid-based cytology and gene rearrangement of aqueous humor cells. UBM may serve as a valuable tool in the diagnosis and serial assessments of anterior segment tumors.

Chemokine and Adhesion Molecule Profiles in Aqueous Humor of Clinically Quiescent Uveitic Cataracts.

PURPOSE: To investigate the chemokine and adhesion molecule profiles in aqueous humor (AH) of eyes with inactive uveitis and their correlations with inflammation relapse after cataract surgery. METHODS: Patients with inactive uveitis who underwent cataract surgery between July 2014 and January 2016 at our center were included. Undiluted AH samples (100-120 µl) were obtained through lateral corneal incisions during surgery, and concentrations of monocyte chemoattractant protein 1 (MCP-1/CCL2), macrophage inflammatory protein 1 (MIP-1), interleukin 8 (IL-8), regulated on activation, normal T cell expressed and secreted (RANTES/CCL5), soluble vascular cell adhesion molecule (sVCAM) and soluble intercellular adhesion molecule (sICAM) were measured by cytometric bead array (BD Bioscience, San Jose, CA). AH levels of these inflammatory factors were compared between different uveitis entities and non-inflammatory control. Risk factors for postoperative inflammation relapse were also analysed in uveitic eyes. RESULTS: As compared with the control group, the panuveitis group had significantly higher aqueous concentrations of MCP-1, IL-8, sVCAM, sICAM; the anterior uveitis group had significantly higher concentrations of MCP-1, MIP-1, sVCAM. Uveitic cataracts with postoperative inflammation relapse had significantly higher levels of MCP-1 and IL-8 in AH than those without. And multivariate cox regression analysis revealed that high AH levels of MCP-1 was an independent predictor for postoperative inflammation relapse. CONCLUSIONS: Clinically quiescent uveitic eyes have elevated levels of chemokines and soluble adhesion molecules in AH, of which MCP-1 is associate with inflammation relapses after cataract surgery.

Longitudinal observation of subretinal fibrosis in Vogt-Koyanagi-Harada disease.

BACKGROUND: Subretinal fibrosis (SRF) is a vision-threatening complication of Vogt-Koyanagi-Harada disease (VKH). It has long been recognized as a sequela of chronic inflammation. The developmental process of SRF, however, has not been described. The purpose of this study is to provide longitudinal observations of SRF in VKH. METHODS: Retrospective chart review of 10 VKH patients referred to our group between January 2008 and September 2015 at acute uveitic stage with SRF at presentation or who developed SRF during follow up. RESULTS: Ten patients (6 males and 4 females) with a median age of 39.0 (range, 23 to 58) years old were included. The median disease duration at presentation and median duration of follow up were 25.5 (range 5 to 60) days and 32.5 (range 13 to 61) months respectively. At presentation, all patients except one had been inappropriately treated with glucocorticosteroid (insufficiently dosed or tapered too fast) for longer than 2 weeks. Despite large dose oral glucocorticosteroid (1 mg/kg/d prednisone or equivalent) with slow tapering in combination with at least one immunomodulatory agent (cyclosporin A, cyclophosphamide or azathioprine) after presentation, all patients developed bilateral SRF within the first 4 months of disease course and 7 patients within the first 2 months. In 8 patients, shape-change/migration and progressive proliferation/pigmentation of SRF was observed over a period of several months after its formation, and then became quiescent but may further underwent depigmentation or pigmentation. SRF involved macula in 12 eyes (7 patients) and caused treatment resistant macular detachment and severe visual impairment in 6 eyes (4 patients). At the last visit, eyes with macular involvement were more common to had worse final best corrected visual acuity (≤20/50) than those without (9/12 vs. 0/8, p = 0.001). CONCLUSIONS: SRF usually develop early in the disease course in VKH patients who are not adequately controlled; it usually undergoes a highly dynamic process within the subretinal space and may involve the macula and resulted in poor final visual outcome.

Visual Prognosis and Associated Factors of Phacoemulsification and Intraocular Lens Implantation in Different Uveitis Entities in Han Chinese.

PURPOSE: To address the visual prognosis and associated predictors of phacoemulsification and intraocular lens implantation in different uveitis entities in Han Chinese. METHODS: A retrospective review of the uveitis patients who underwent phacoemulsification and intraocular lens implantation in our center between 2004 and 2014. RESULTS: The 158 patients (226 eyes) included anterior uveitis (45 eyes), posterior/pan-uveitis (61 eyes), Vogt-Koyanagi-Harada disease (79 eyes) and Behçet disease (41 eyes). At 6 months after surgery, best-corrected visual acuity (BCVA) significantly improved (p < 0.001) in all uveitis groups with 134 (59.3%) eyes achieving 20/40 or better. The anterior uveitis and Behçet disease groups had significantly better and worse visual outcomes than other groups, respectively. Poor preoperative BCVA, macular lesions, and secondary glaucoma were independent variables that predicted a poor visual outcome. CONCLUSIONS: Our current study revealed a generally favorable outcome and associated predictors of phacoemulsification and intraocular lens implantation in uveitic cataracts in Han Chinese.

Clinical Patterns of Uveitis in a Tertiary Center in North China.

PURPOSE: To analyze the spectrum of uveitis at a tertiary hospital in northern China. METHODS: This study is a retrospective study from June 2014 to February 2015. A total of 606 consecutive patients with uveitis were screened for etiologies and classified according to the anatomic sites of inflammation. RESULTS: The mean age at presentation was 33.8 ± 15.5 years old. Males and females were almost equally affected. Panuveitis was the most common anatomic diagnosis, followed by anterior, posterior, and intermediate uveitis. VKH syndrome, Behçet disease and idiopathic anterior uveitis were the most common uveitis entities. Ocular complications were detected in 441 patients. CONCLUSIONS: More than half of the patients with uveitis from northern China had an identifiable cause or was diagnosed as a specific disease entity with VKH and BD among the major etiologies. Cataract, steroid-induced ocular hypertension and macular edema were the leading complications.