Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model.

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.

Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development.

Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4+ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72+CD11c+ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4+ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.

A Period of Macular Hyperemia and Subclinical Edema Caused by Phacoemulsification Surgery in Noninfectious Uveitis.

PURPOSE: To identify the changes in macular microvasculature in uveitic patients following phacoemulsification. METHODS: A prospective cohort study was conducted by enrolling uveitic patients who underwent phacoemulsification at the Eye Hospital. Macular vessel densities (VD) of superficial and deep capillary plexus (SCP and DCP) and retinal thickness (RT) were quantified by optical coherence tomographic angiography (OCTA). RESULTS: Twenty-one eyes obtained satisfactory OCTA scans at all the follow-up visits. After surgery, an increasing trend in SCP VD was found (p = .037) and reached its maximum (+2.79 ± 4.86%) at post-3 months (M). RT increased synchronously. The increases in SCP VD at post-3 M were significantly correlated with the changes in anterior chamber cells (ACCs) at post-1 M and 2 M (r = 0.450, p = .041; r = 0.477, p = .029, respectively). CONCLUSIONS: Inflammation generates a long-term effect on retina demonstrated as an increase in SCP VD and RT which are associated with synchronous ACCs changes after phacoemulsification.

Comparison of the Three Sets of Diagnostic Criteria for Vogt-Koyanagi-Harada Disease in Southeast China - A Retrospective Case-Control Study.

PURPOSE: To compare the utility of the Chinese diagnostic criteria for Vogt-Koyanagi-Harada (VKH) disease (CDCV), the revised diagnostic criteria (RDC) and the classification criteria by SUN (SUN-C). METHODS: Two groups of patients (VKH group and non-VKH group) were assessed in this retrospective case-control study. Sensitivity, specificity and area under receiver operating characteristic curve (AUC) were evaluated among these criteria. RESULTS: 258 patients were included after propensity score matching. The sensitivities were 92.2% in CDCV, 66.7% in RDC, and 54.3% in SUN-C. In different disease stages (early and late), similar sensitivity results were observed. The specificities were 96.1% in CDCV, 97.7% in RDC, and 99.2% in SUN-C. The AUCs were 0.942 in CDCV, 0.822 in RDC and 0.767 in SUN-C. CONCLUSION: A higher sensitivity value and larger AUC in CDCV were found. CDCV are highly useful in the diagnosis and classification of VKH disease in Chinese patients.

In Situ Forming Hydrogel as a Tracer and Degradable Lacrimal Plug for Dry Eye Treatment.

Lacrimal plug is an effective and widely therapeutic strategy to treat dry eye. However, almost all commercialized plugs are fixed in a certain design and associated with many complications, such as spontaneous plug extrusion, epiphora, and granuloma and cannot be traced in the long-term. Herein, a simple in situ forming hydrogel is developed as a tracer and degradable lacrimal plug to achieve the best match with the irregular lacrimal passages. In this strategy, methacrylate-modified silk fibroin (SFMA) is served as a network, and a self-assembled indocyanine green fluorescence tracer nanoparticle (FTN) is embedded as an indicator to develop the hydrogel plug using visible photo-crosslinking. This SFMA/FTN hydrogel plug has excellent biocompatibility and biodegradability, which can be noninvasively monitored by near-infrared light. In vivo tests based on dry eye rabbits show that the SFMA/FTN hydrogel plug can completely block the lacrimal passages and greatly improve the various clinical indicators of dry eye. These results demonstrate that the SFMA/FTN hydrogel is suitable as an injectable and degradable lacrimal plug with a long-term tracking function. The work offers a new approach to the development of absorbable plugs for the treatment of dry eye.

Contrast Sensitivity Deficits and Its Structural Correlates in Fuchs Uveitis Syndrome.

Purpose: To investigate the deficits in contrast sensitivity in patients with Fuchs uveitis syndrome (FUS) and to explore the potential relationship between contrast sensitivity and ocular structure. Methods: In this prospective study, 25 patients with FUS and 30 healthy volunteers were recruited. Eyes were divided into three groups: FUS-affected eyes (AE), fellow eyes (FE), and healthy eyes. The contrast sensitivity function (CSF) of all participants was evaluated using the quick CSF (qCSF) method. Fundus photographs were collected for the analysis of refractive media, and vascular density (VD) was assessed using optical coherence tomography angiography (OCTA). Data were analyzed and compared using the generalized estimating equation (GEE). Results: The CSF of AE was significantly lower than that of FE and controls, while no significant difference was observed between FE and controls. Contrast sensitivity was negatively correlated with the grade of haze. No significant correlation was found between visual function and VDs in FUS eyes. Conclusions: We found that the CSF of FUS-affected eyes was significantly reduced, and the visual impairment was predominantly caused by the refractive media turbidity.

Clinical outcomes of single-step transepithelial photorefractive keratectomy and off-flap epipolis-laser in situ keratomileusis in moderate to high myopia: 12-month follow-up.

BACKGROUND: To compare the quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TPRK) and off-flap epipolis-laser in situ keratomileusis (Epi-LASIK) in moderate to high myopia. METHODS: In this prospective self-control study, we included patients with moderate to high myopia who were randomized to undergo TPRK in one eye and Epi-LASIK in the other eye. Twelve-month follow-up results for visual acuity, refraction, ocular high-order aberrations, contrast sensitivity, postoperative pain, epithelial healing, and haze grade were assessed. RESULTS: A total of 64 eyes (32 patients) were enrolled in the study. More eyes completed re-epithelialization in the TPRK group than in the Off-flap Epi-LASIK group 3-4 days postoperatively, while all eyes completed re-epithelialization by 7 days. More eyes achieved a visual acuity (both UDVA and CDVA) of better than 20/20 in the TPRK group than in the Off-flap Epi-LASIK group. The ±0.50 D predictability for correction of the spherical equivalent (SE) was higher in the eyes of the TPRK group (91%) than in those of the off-flap Epi-LASIK group (80%) 12 months after surgery. No significant differences in ocular aberrations, including coma, spherical, and trefoil, were found between the two groups at 12 months. There were also no significant differences in visual acuity, contrast sensitivity, pain, and haze grading between the two groups. CONCLUSIONS: Both TPRK and off-flap Epi-LASIK are safe, effective, and predictable treatments for moderate to high myopia with comparable surgical outcomes. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrial.gov ( NCT05060094 , 17/09/2021).

Immunoregulation in Diabetic Wound Repair with a Photoenhanced Glycyrrhizic Acid Hydrogel Scaffold.

M1 macrophage accumulation and excessive inflammation are commonly encountered issues in diabetic wounds and can fail in the healing process. Hence, hydrogel dressings with immunoregulatory capacity have great promise in the clinical practice of diabetic wound healing. However, current immunoregulatory hydrogels are always needed for complex interventions and high-cost treatments, such as cytokines and cell therapies. In this study, a novel glycyrrhizic acid (GA)-based hybrid hydrogel dressing with intrinsic immunoregulatory properties is developed to promote rapid diabetic wound healing. This hybrid hydrogel consists of interpenetrating polymer networks composed of inorganic Zn2+ -induced self-assembled GA and photo-crosslinked methyl acrylated silk fibroin (SF), realizing both excellent injectability and mechanical strength. Notably, the SF/GA/Zn hybrid hydrogel can regulate macrophage responses in the inflammatory microenvironment, circumventing the use of any additives. The immunomodulatory properties of the hydrogel can be harnessed for safe and efficient therapeutics that accelerate the three phases of wound repair and serve as a promising dressing for the management of diabetic wounds.

Synergistic Effect of Combined Sub-Tenon Triamcinolone and Intravitreal Anti-VEGF Therapy for Uveitic Macular Edema.

Purpose: To investigate effects of intravitreal anti-VEGF in combination therapy with sub-Tenon triamcinolone acetonide (STA) injection for uveitic macular edema (UME). Design: A single-center, retrospective cohort study. Methods: The medical records were obtained for 65 eyes of 65 patients with UME. Of which, 32 eyes received combined anti-VEGF with STA injection, and 33 eyes received 40 mg of STA injection alone. The primary outcome was the reduction of central macular thickness (CMT) measured with optical coherence tomography (OCT). Resolution rate of clinical UME and changes of best corrected visual acuity (BCVA) over 24 weeks were secondary outcomes. Results: There was a significantly greater reduction of CMT with the combination treatment than with STA alone at 1-week (ß = -157.9, P < 0.001) and 1-month (ß = -53.1, P = 0.019) after injection. The cumulative incidence of macular edema resolution of all eyes was 87.7%, with 90.6% (29/32) in the combined group and 84.8% (28/33) in the STA group, respectively. More incidence of UME resolution was observed in the combined group than the STA group after 1 week (71.9% vs 15.2%, P < 0.001) and 4 weeks (84.4% vs 54.5%, P = 0.009), respectively. BCVA was better for the combination treatment than STA alone at 1-week (ß = -0.085, P = 0.070) and 1-month (ß = -0.108, P = 0.019) after injection, respectively. Increased intraocular pressure (>25 mmHg) was observed in 4 eyes (12.5%) in the combined group and 5 eyes (15.2%) in the STA group, respectively. Conclusion: Combined intravitreal anti-VEGF and STA is superior to STA alone for reduction of UME and visual restoration. Addition of anti-VEGF did not increase risk for steroid-induced elevation of intraocular pressure over 6 months.

Ganciclovir attenuates the onset and progression of experimental autoimmune uveitis by inhibiting infiltration of Th17 and inflammatory cells into the retina.

Noninfectious (autoimmune and immune-mediated) uveitis is one of the primary diseases leading to blindness in the world. Due to the limitation of current first-line drugs for clinical uveitis, novel drugs and targets against uveitis are urgently needed. Ganciclovir (GCV), an FDA-approved antiviral drug, is often used to treat cytomegalovirus-induced retinitis in clinical patients. Recently, GCV was found to suppress neuroinflammation via targeting STING signaling because the STING pathway plays a pivotal role in autoimmune diseases. However, until now, the effect of GCV on non-infectious uveitis has never been explored. In this work, using the rat experimental autoimmune uveitis (EAU) model, we first found STING to be highly expressed in infiltrating cells (CD68+, CD45+, and CD4+) and retinal glial cells (Iba1+ and GFAP+) of the immunized retina. More importantly, GCV treatment can significantly suppress the initiation and progression of EAU by inhibiting infiltration of Th17 and inflammatory cells into the retina. Mechanistically, we found that GCV could reverse the levels of pro-inflammatory factors (such as IL-1ß) and chemokine-related factors (such as Cxcr3), possibly via targeting the STING pathway. The present results suggest that GCV may be considered as a novel therapeutic strategy against human uveitis.

A Novel Clinical Five-Risk Factor Panel for Individualized Recurrence Risk Assessment of Patients With Acute Anterior Uveitis.

Purpose: Detecting and managing relapses of acute anterior uveitis (AAU) is necessary for improving follow-up planning to minimize recurrences and further complications. However, reliable clinical and laboratory risk factors are lacking, as is a predictive model for use in clinical practice that is capable of identifying patients at high risk for recurrence after remission. Methods: We analyzed 38 laboratory parameters and clinical data from a large longitudinal retrospective cohort of 233 patients with AAU. Association of laboratory parameters with recurrence-free survival (RFS) was evaluated using univariate Cox proportional hazards regression. A clinically applicable predictive model was developed using a logistic regression model. Results: Of the 38 laboratory parameters studied, we identified 5 parameters (HDL, ankylosing spondylitis, HLA-B27, MO, and LDL) to be associated with RFS. We developed a clinical five-risk factor panel (5RF-panel), which was capable of effectively distinguishing recurrent patients from nonrelapsed patients (area under the curve [AUC] = 0.837), as well as between patients with high and low risks of AAU recurrence (hazard ratio [HR] = 45.874, 95% confidence interval [CI] = 5.232-402.2, P < 0.001). The robust performance of the 5RF-panel was further validated in the testing cohort (AUC = 0.725, and HR = 51.982, 95% CI = 4.438-608.9, P = 0.024). Furthermore, the 5RF-panel demonstrated superior performance in stratifying recurrence risk based on known risk factors. Conclusions: We identified and validated a novel clinical 5RF-panel to predict individualized risk of AAU recurrence and improved patient classification for clinical management. Translational Relevance: The present study identified and validated a 5RF-panel that is a promising individualized predictive tool to monitor recurrence risk and guide personalized management of patients with AAU.

Evaluation of microvasculature alterations in convalescent Vogt-Koyanagi-Harada disease using optical coherence tomography angiography.

PURPOSE: To evaluate the microvasculature alterations in convalescent Vogt-Koyanagi-Harada (VKH) disease using optical coherence tomography angiography (OCTA), and to explore the association between microvasculature and the presence of sunset glow fundus (SGF). METHODS: A cross-sectional study was conducted with 28 VKH patients at convalescent stage and 25 healthy individuals. Both eyes of each participant were enrolled. The VKH patients were classified into two subgroups based on the existence of SGF. OCTA images (3 × 3 mm) were assessed for the data of superficial capillaris plexus (SCP), deep capillaris plexus (DCP), choriocapillaris, and foveal avascular zone (FAZ). RESULTS: Compared with healthy control eyes and eyes without SGF, the vessel densities of the SCP and DCP decreased significantly in most regions of eyes with SGF (p < 0.0167). No significant difference of vascular perfusion was found between eyes without SGF and control eyes (p > 0.05). VKH patients with SGF had slightly increased FAZ area (p = 0.067) and decreased choroid flow area (p = 0.427) than those in the control group. CONCLUSION: Convalescent VKH patients with SGF showed decreased macular capillary perfusion. OCTA could serve as a sensitive tool to assess the microvasculature alterations of VKH disease.

Economic Hardship, Ocular Complications, and Poor Self-reported Visual Function are Predictors of Mental Problems in Patients with Uveitis.

Purpose: To characterize the quality of life and mental health status of patients with uveitis and investigate predictors of psychological problems.Methods: A total of 245 patients and 105 controls were enrolled in this cross-sectional study. Quality of life, psychological status, socio-demographic and clinical data were obtained from questionnaires and medical records. Multivariate regression analyses and Receiver Operating Characteristic (ROC) were applied to obtain the model predicting psychological problems of patients.Results: Of 245 patients, 16.7% and 26.5% (P< .0001) screened positive for anxiety and depression, respectively. The model predicting anxiety was comprised of low annual household income and poor self-reported visual function (P= .029,P< .0001, respectively), with an AUC of ROC of 0.744. The model predicting depression was comprised of poor self-reported visual function and ocular complications (P< .0001, P= .012, respectively), with an AUC of 0.78.Conclusions: Economic hardship, ocular complications, and poor self-reported visual function are predictors of mental problems in patients with uveitis.

Glycol chitosan/oxidized hyaluronic acid hydrogel film for topical ocular delivery of dexamethasone and levofloxacin.

In the present study, we fabricated a glycol chitosan/oxidized hyaluronic acid hydrogel film with promising potential for the dual ophthalmic delivery of dexamethasone (Dex) and levofloxacin (Lev). Utilizing different oxidation degrees of oxidized hyaluronic acid (OHA), several blank hydrogel films and Lev-loaded hydrogel films were successfully fabricated. With an increase in the oxidation degree of OHA, the swelling ratio of the hydrogel films decreased accordingly. The hydrogel films displayed a stepwise release of Lev and Dex, with Lev rapidly released from the hydrogel film, followed by a sustained release of Dex. Lev-loaded hydrogel films revealed a potent capacity to inhibit bacterial growth in different bacterial strains. In lipopolysaccharide-activated RAW264.7 macrophages, the formulated hydrogel films displayed potent in vitro anti-inflammatory activity by significantly downregulating various inflammatory cytokines. Overall, the fabricated hydrogel film acting as a dual drug delivery system might be a promising vehicle for the treatment of postoperative endophthalmitis.

Preparation and characterization of a pterostilbene-peptide prodrug nanomedicine for the management of dry eye.

In the present study, a pterostilbene-peptide amphiphile (PS-GA-RGD) that can spontaneously self-assemble into prodrug nanomedicine, was rationally designed and developed as a novel ophthalmic formulation for the potential management of dry eye. The formed PS-GA-RGD nanomedicine was characterized by dynamic latter scattering (DLS) and transmission electron microscopy (TEM). After esterase treatment, active pterostilbene (PS) sustainably released from the PS-GA-RGD nanomedicine within 48 h, as indicated by an in vitro release study. In comparison with native PS, the formed PS-GA-RGD nanomedicine caused minimal cytotoxicity towards RAW 264.7 and HCEC cells in the 0-20 µM range and did not delay wound healing of HCEC monolayer within 6 h. Furthermore, PS-GA-RGD nanomedicine effectively reduced the intracellular reactive oxygen species (ROS) level in H2O2 challenged RAW264.7 macrophages and remarkably suppressed the secretion of inflammatory cytokines (e.g., NO, TNF-α, and IL-6) in lipopolysaccharide (LPS) activated RAW264.7 macrophages. Ocular tolerance to the proposed PS-GA-RGD nanomedicine was good after a single instillation in in vivo ocular irritation tests. Overall, the proposed PS-GA-RGD nanomedicine had potent anti-oxidant capacity and anti-inflammatory efficacy, which may be a promising ophthalmic formulation for the management of dry eye.

A combination of inhibiting microglia activity and remodeling gut microenvironment suppresses the development and progression of experimental autoimmune uveitis.

Noninfectious (autoimmune and immune-mediated) uveitis is an ocular inflammatory disease which can lead to blindness in severe cases. Due to the potential side effects of first-line drugs for clinical uveitis, novel drugs and targets against uveitis are still urgently needed. In the present study, using rat experimental autoimmune uveitis (EAU) model, we first found that minocycline treatment can substantially inhibit the development of EAU and improve the retinal function by suppressing the retinal microglial activation, and block the infiltration of inflammatory cells, including Th17, into the retina by decreasing the major histocompatibility complex class II (MHC II) expression in resident and infiltrating cells. Moreover, we demonstrated that minocycline treatment can remodel the gut microenvironment of EAU rats by restoring the relative abundance of Ruminococcus bromii, Streptococcus hyointestinalis, and Desulfovibrio sp. ABHU2SB and promoting a functional shift in the gut via reversing the levels of L-proline, allicin, aceturic acid, xanthine, and leukotriene B4, and especially increasing the production of propionic acid, histamine, and pantothenic acid. At last, we revealed that minocycline treatment can significantly attenuate the progression of EAU after inflammation onset, which may be explained by the role of minocycline in the remodeling of the gut microenvironment since selective elimination of retinal microglia on the later stages of EAU was shown to have little effect. These data clearly demonstrated that inhibition of microglial activation and remodeling of the gut microenvironment can suppress the development and progression of experimental autoimmune uveitis. Considering the excellent safety profile of minocycline in multiple clinical experiments, we suggest that minocycline may have therapeutic implications for clinical uveitis.

Effects of Terminal Motif on the Self-Assembly of Dexamethasone Derivatives.

Tailoring the terminal motif of molecules including drugs might significantly affect their self-assembly tendency in aqueous solution, thus providing a rational strategy to modulate its macroscopic characteristics of supramolecular assembly. A model drug of dexamethasone (Dex) was esterified by different fatty acids [succinic acid (SA), glutaric acid (GA), and adipic acid (AA)] and aromatic acid [phthalic acid (PA)] to generate a series of Dex derivatives. Aqueous solution of Dex-SA, Dex-GA, and Dex-AA turned into hydrogel spontaneously after a period time of incubation (24, 48, and 72 h, respectively) via the auto-hydrolytic strategy, while aqueous solution of Dex-PA did not result in hydrogelation during 3 days of incubation. Aqueous solutions of Dex-SA, Dex-GA, and Dex-AA underwent apparent hydrolysis (10.73 ± 0.64%, 15.17 ± 2.24%, and 17.29 ± 1.39%, respectively), while Dex-PA exhibited a minimal hydrolysis (<1%) in a period of 28 days study, as indicated by in vitro hydrolytic test. Morphological observation showed that the hydrogel formed by Dex-SA was composed of uniform nanofibers, while hydrogels formed by Dex-GA, and Dex-AA were derived from irregular particles. The mechanical strength of hydrogel formed by Dex-SA was much bigger than that of hydrogels formed by Dex-GA and Dex-AA, as indicated by rheological test. Moreover, the acylation of Dex did not compromise its potent anti-inflammatory activity in a lipopolysaccharide (LPS)-activated RAW 264.7 macrophage.

Mucoadhesive dexamethasone-glycol chitosan nanoparticles for ophthalmic drug delivery.

Self-assembly of drug-polysacrrides conjugates forming nanostructures provides a simple and promising strategy for the extension of precorneal retention and enhancement of corneal permeability. In the present study, a series of dexamethasone-glycol chitosan (Dex-GCS) conjugates were synthesized and thoroughly characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and ultraviolet-visible (UV-Vis) spectroscopy. The resulting Dex-GCS conjugates were able to self-assemble into nanoparticles spontaneously with particle sizes in the range of 277-289 nm and a positive charge of approximately +15 mV. Roughly spherical nanoparticles were observed by transmission electron microscopy (TEM). The in vitro mucoadhesive properties of Dex-GCS nanoparticles were evaluated by recording the variations in the zeta potential after incubation with different concentrations of mucin. In vitro release studies performed in phosphate-buffered saline (PBS, pH = 7.4) indicated progressive Dex release up to 8 h, followed by a plateau up to 48 h. Dex-GCS nanoparticles caused slight cytotoxicity against L929, HCEC and RAW 264.7 cells after 24 h of incubation and displayed a nearly identical anti-inflammatory efficacy to dexamethasone sodium phosphate (Dexp) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. More importantly, the proposed Dex-GCS nanoparticles showed good ocular tolerance and provided a relatively longer precorneal duration compared with that of the aqueous solution formulation, which suggested that the self-assembled Dex-GCS nanoparticle might be a promising candidate for ophthalmic drug delivery.

Correlation of serum amyloid A levels, clinical manifestations, treatment, and disease activity in patients with acute anterior uveitis.

PURPOSE: To investigate the association between serum amyloid A (SAA) protein and the clinical features of acute anterior uveitis (AAU), and to evaluate the disease activity and treatment effect in relation to SAA levels. METHODS: AAU patients and healthy individuals were recruited from October 2016 to August 2017 at the Department of Uveitis, in the Eye Hospital of Wenzhou Medical University. Related demographic, clinical characteristics, and therapeutic data were analyzed. RESULTS: One hundred and eight AAU patients and 18 healthy controls were included in this study. Serum SAA levels in AAU patients were significantly higher than those of healthy controls (p all < 0.0001). Significantly higher SAA levels were found in AS+AAU patients than those in AS-AAU patients (p < 0.05). SAA levels were also significantly higher in patients with HLA-B27+AAU compared with those with HLA-B27-AAU (p < 0.05). Furthermore, in each of the AAU subgroups, higher SAA levels were observed in the active state than those in the inactive state (p all < 0.05). In addition, SAA levels were positively correlated to anterior chamber cell counts (r = 0.492, p < 0.0001). ROC curve analysis revealed that SAA had an AUC value of 0.727 for detecting active inflammation (Youden's index = 0.38). SAA decreased with effective treatments (p = 0.0002). CONCLUSION: Serum levels of SAA were elevated in AAU patients. The increased levels of SAA were correlated with AS and HLA-B27 status. SAA levels were also positively correlated to disease activity and decreased with effective treatments. These findings suggest that SAA is associated with AAU, with a potential role in monitoring inflammatory processes and assessing the efficacy of therapy.

Inner Retinal Microvasculature Damage Correlates With Outer Retinal Disruption During Remission in Behçet's Posterior Uveitis by Optical Coherence Tomography Angiography.

Purpose: To quantify the inner retinal vascular changes that occur in the superficial and deep layers in patients with Behçet's disease (BD) in remission using optical coherence tomography angiography (OCTA) and to evaluate the associations with outer retinal structure. Methods: Nineteen eyes from 19 patients with BD in remission were enrolled, including 10 eyes with less than five ocular attacks (n < 5) and nine eyes with five or more attacks (n ≥ 5). The foveal avascular zone (FAZ) and global and regional vessel density (VD) in both layers were compared between BD eyes and normal eyes. Their outer retinal structure, including integrity of the ellipsoid zone (EZ), interdigitation zone (IZ), and outer retinal layer thickness were evaluated. Associations between the inner retinal vasculature and outer retinal disruption were sought. Results: Compared to normal eyes, except for the nasal region, all deep capillary VD values were lower in the BD groups, especially in the inferior region. In the superficial layer, the VD differences between groups were larger in capillaries than in small vessels. The FAZ in the n ≥ 5 group was larger than that in normal and the n < 5 groups in the deep layer. Greater disruption of EZ and IZ was correlated with decreasing global and regional deep capillary VD. Conclusions: BD Patients in remission had significant changes in the inner retinal vasculature that corresponded to the outer retinal disruption. Quantitative measurement by OCTA and algorithm might be useful for evaluation of the vasculature and pathologic changes in BD.