The Combination of Bacillus natto JLCC513 and Ginseng Soluble Dietary Fiber Attenuates Ulcerative Colitis by Modulating the LPS/TLR4/NF-κB Pathway and Gut Microbiota.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is currently difficult to treat effectively. Both Bacillus natto (BN) and ginseng-soluble dietary fiber (GSDF) are anti-inflammatory and helps sustain the intestinal barrier. In this study, the protective effects and mechanism of the combination of B. natto JLCC513 and ginseng-soluble dietary fiber (BG) in DSS-induced UC mice were investigated. Intervention with BG worked better than taking BN or GSDF separately, as evidenced by improved disease activity index, colon length, and colon injury and significantly reduced the levels of oxidative and inflammatory factors (LPS, ILs, and TNF-α) in UC mice. Further mechanistic study revealed that BG protected the intestinal barrier integrity by maintaining the tight junction proteins (Occludin and Claudin1) and inhibited the LPS/TLR4/NF-κB pathway in UC mice. In addition, BG increased the abundance of beneficial bacteria such as Bacteroides and Turicibacter and reduced the abundance of harmful bacteria such as Allobaculum in the gut microbiota of UC mice. BG also significantly upregulated genes related to linoleic acid metabolism in the gut microbiota. These BG-induced changes in the gut microbiota of mice with UC were significantly correlated with changes in pathological indices. In conclusion, this study demonstrated that BG exerts protective effect against UC by regulating the LPS/TLR4/NF-κB pathway and the structure and metabolic function of gut microbiota. Thus, BG can be potentially used in intestinal health foods to treat UC.

Ultra-Thin and Broadband P-Band Metamaterial Absorber Based on Carbonyl Iron Powder Composites.

The field of P-band (0.3-1 GHz) absorption has witnessed rapid development in metamaterial absorbers due to their exceptional designability and the absence of restrictions imposed by the one-fourth wavelength rule. In this study, we combined carbonyl iron powder (CIP) composites with a periodic structure composed of metal capacitive patterns and employed a genetic algorithm (GA) to optimize the electromagnetic parameters of the CIP substrate. By selecting the appropriate shape and material for the units of pattern based on transmission line theory, as well as regulating relevant structural parameters, we successfully designed an ultra-thin broadband metamaterial absorber for the P-band. Experimental results demonstrate that within the range of 0.3-0.85 GHz, the reflection loss of our absorber remains below -5 dB, with a maximum value of -9.54 dB occurring at 0.45 GHz. Remarkably, this absorber possesses a thickness equivalent to only 1/293 of its working wavelength. Then, we conducted analyses on electric field distribution, magnetic field distribution, and energy loss density. Our findings suggest that high-performance absorption in metamaterials can be attributed to λ/4 resonant or coupling effects between structural units or diffraction phenomena. This absorber offers several advantages, including broad low-frequency absorption capability, ultra-thin profile, and convenient fabrication process, thus providing valuable theoretical insights for designing metamaterial structures.

E3 ubiquitin ligase Herc3 deficiency leads to accumulation of subretinal microglia and retinal neurodegeneration.

Activated microglia have been implicated in the pathogenesis of age-related macular degeneration (AMD), diabetic retinopathy, and other neurodegenerative and neuroinflammatory disorders, but our understanding of the mechanisms behind their activation is in infant stages. With the goal of identifying novel genes associated with microglial activation in the retina, we applied a semiquantitative fundus spot scoring scale to an unbiased, state-of-the-science mouse forward genetics pipeline. A mutation in the gene encoding the E3 ubiquitin ligase Herc3 led to prominent accumulation of fundus spots. CRISPR mutagenesis was used to generate Herc3-/- mice, which developed prominent accumulation of fundus spots and corresponding activated Iba1 + /CD16 + subretinal microglia, retinal thinning on OCT and histology, and functional deficits by Optomotory and electrophysiology. Bulk RNA sequencing identified activation of inflammatory pathways and differentially expressed genes involved in the modulation of microglial activation. Thus, despite the known expression of multiple E3 ubiquitin ligases in the retina, we identified a non-redundant role for Herc3 in retinal homeostasis. Our findings are significant given that a dysregulated ubiquitin-proteasome system (UPS) is important in prevalent retinal diseases, in which activated microglia appear to play a role. This association between Herc3 deficiency, retinal microglial activation and retinal degeneration merits further study.

Impact of COVID-19-related lifestyle changes on diabetic macular edema.

AIM: To assess diabetic macular edema (DME) progression during the early phases of the COVID-19 pandemic, when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions, particularly those requiring frequent office visits. METHODS: This is a multicenter retrospective chart review of 370 patients (724 eyes) with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021. Period 1 was January 2019 to February 2020 (considered pre-COVID-19), period 2 was March 2020 to December 2020 (considered the height of the pandemic; highest level of pandemic-related clinical and societal regulations) and period 3 was January 2021 to July 2021 (re-adjustment to the new "pandemic norms"). Main outcome measures included visual acuity, body mass index (BMI), blood pressure (BP), hemoglobin A1c (HbA1c), macular thickness, patient adherence to scheduled ophthalmology visits, and DME treatment(s) received at each visit. To facilitate measurement of macular thickness, each macula was divided into 9 Early Treatment Diabetic Retinopathy Study (ETDRS)-defined macular sectors as measured by OCT imaging. RESULTS: There was no change of BMI, systolic BP, and diastolic BP between any of the time periods. HbA1c showed a very small increase from period 1 (7.6%) to period 2 (7.8%, P=0.015) and decreased back to 7.6% at period 3 (P=0.12). Macular thickness decreased for 100% of macular regions. The central macular thickness decreased across all 3 periods from 329.5 to 316.6 µm (P=0.0045). After analysis of multiple variables including HbA1c, BMI, adherence to scheduled appointments, different clinic centers, and treatment interventions, there was no easily identifiable subgroup of patients that experienced the increase in DME. CONCLUSION: DME doesn't worsen during the COVID-19 pandemic, instead sustaining a very small but statistically significant improvement. While identifying a mechanism behind our findings is beyond the scope of this study, potential explanations may include a delay in retinal changes beyond our study period, an unexpected increase in treatment frequency despite pandemic restrictions, and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.

Pediatric Rhegmatogenous Retinal Detachments: Etiologies, Clinical Course, and Surgical Outcomes.

Purpose: To describe the predisposing factors, clinical course, and surgical methods of pediatric rhegmatogenous retinal detachment (RRD) and determine which factors affect anatomic success. Methods: Data of patients 18 years or younger who had surgical repair for RRD from January 1, 2004, to June 31, 2020, with a minimum of 6 months of follow-up were retrospectively analyzed. Results: The study evaluated 101 eyes of 94 patients. Of the eyes, 90% had at least 1 predisposing factor to pediatric RRD, including trauma (46%), myopia (41%), prior intraocular surgery (26%), and congenital anomaly (23%); 81% had macula-off detachments and 34% had proliferative vitreoretinopathy (PVR) grade C or worse at presentation. The presence of PVR grade C or worse (P = .0002), total RRD (P = .014), and vitrectomy alone at first surgery (P = .0093) were associated with worse outcomes. Patients who had scleral buckle (SB) alone at the first surgery had statistically higher rates of anatomic success than those who had vitrectomy alone or combined with SB (P = .0002). After the final surgery, 74% of patients achieved anatomic success. Discussion: The majority of cases in this study were associated with 1 of the 4 risk factors predisposing to pediatric RRD. These patients often present late with macula-off detachments and PVR grade C or worse. The majority of patients achieved anatomic success after surgical repair using SB, vitrectomy, or a combination.

Comparison of Surgical Outcomes for Uncomplicated Primary Retinal Detachment Repair.

Purpose: To compare the outcomes of primary uncomplicated rhegmatogenous retinal detachment (RRD) repair using pars plana vitrectomy (PPV), scleral buckling (SB), or combined scleral buckling with vitrectomy (SB/PPV). Patients and Methods: Single-institution, retrospective, observational study of 179 patients with primary RRD managed at a large academic hospital system. We excluded patients with less than 6 months of follow-up, previous vitrectomy or buckle, giant retinal tears, aphakia, recurrent forms of RRD, or extensive proliferative vitreoretinopathy (Grade C or worse) documented on exam or requiring membrane peel. Outcome measures included primary anatomical success at 6 months, functional success defined as BCVA ≥ 20/200, and best corrected visual acuity (BCVA) using logMAR scoring. Subgroup analysis was performed in the following patient groups: phakic, pseudophakic, inferior detachments, and prior pneumatic retinopexy. Results: Primary anatomical success was achieved in 145 of 179 eyes (81.0%), with SB/PPV showing a significantly greater success rate (p = 0.046) when compared to SB and PPV. Functional success was achieved in 137 of the 145 anatomically successful eyes (94.5%), with values ranging between 92% and 97% amongst the interventions (p = 0.552). No difference was found in final BCVA (p = 0.367). Patients with inferior detachment had an odds ratio of 2.15 for primary anatomic failure. Prior pneumatic retinopexy did not significantly affect any of the primary outcomes. Conclusion: SB/PPV yielded a significantly better primary anatomical success rate when compared to SB and PPV. Functional success and final BCVA was similar amongst the interventions. Inferior detachments were associated with worse primary anatomic outcomes. Prior pneumatic retinopexy did not significantly affect surgical outcomes.

Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

OBJECTIVE: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed. RESULTS: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40). CONCLUSIONS: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.

Retinal Hemorrhages During Examination for Retinopathy of Prematurity: A Form of Ocular Decompression Retinopathy.

Purpose: Posterior segment hemorrhage occurring during or shortly after examination (PSHE) for retinopathy of prematurity (ROP) is a very rare complication. We present a case of and review the literature on PSHE during ROP examination to better characterize this complication. Methods: A case report is presented, followed by a review of similar cases in the literature. Results: An infant undergoing laser photocoagulation for ROP rapidly developed diffuse intraretinal hemorrhages in his right eye during the laser and after a Valsalva event while he was intubated under general anesthesia. The hemorrhages resolved within 1 week. This presentation was similar to those in previously reported cases. Conclusions: PSHE in ROP usually consists of multiple, diffuse, intraretinal hemorrhages that occur within minutes of ROP examination and resolve within a few weeks without any other ocular findings or sequelae. PSHE seems to represent a form of ocular decompression retinopathy.

TOXIC POSTERIOR SEGMENT SYNDROME AFTER DROPLESS CATARACT SURGERY WITH COMPOUNDED TRIAMCINOLONE-MOXIFLOXACIN.

PURPOSE: To report toxic posterior segment syndrome after dropless cataract surgery using locally compounded triamcinolone-moxifloxacin. METHODS: A retrospective case review of 7 patients presenting with a decrease in visual acuity after dropless cataract surgery. RESULTS: All patients experienced significant reductions in best-corrected visual acuity of the postoperative eye ranging from 20/40 to count finger at 4 feet (average best-corrected visual acuity 20/220) immediately after surgery. The presenting symptoms included flashes, floaters, photophobia, glare, halos, visual distortions, and problems assessing colors. In three cases, foveal retinal pigment epithelium changes were noted on dilated fundus exam (DFE). Ellipsoid zone loss was noted on ocular coherence tomography in five of the seven affected eyes. Electrophysiology testing in five of the seven affected eyes demonstrated large decreases in full-field electroretinogram amplitude, oscillatory potentials, multifocal electroretinogram, and visual evoked potential, along with a negative electroretinogram. One patient was treated with a dexamethasone implant, but no improvement in visual acuity was noted. CONCLUSION: This is the first case series of toxic posterior segment syndrome occurring secondary to intracameral compounded triamcinolone-moxifloxacin in dropless cataract surgery. The FDA has attributed the toxicity to abnormally high levels of the binding agent poloxamer 407 in the compounded medication. Clinicians should be aware of this phenomenon and exhibit caution when using compounded medications.

Mice With a Combined Deficiency of Superoxide Dismutase 1 (Sod1), DJ-1 (Park7), and Parkin (Prkn) Develop Spontaneous Retinal Degeneration With Aging.

Purpose: Chronic oxidative stress is an important mechanism of disease in aging disorders. We do not have a good model to recapitulate AMD and other retinal disorders in which chronic oxidative stress plays an important role. We hypothesized that mice with a combined deficiency in superoxide dismutase 1 (Sod1), DJ-1 (Park-7), and Parkin (Prkn) (triple knock out, TKO) would have an increased level of chronic oxidative stress in the retina, with anatomic and functional consequences just with aging. Methods: Eyes of TKO and B6J control mice were (1) monitored with optical coherence tomography (OCT) and electroretinography (ERG) over time, and (2) collected for oxidative marker protein analysis by ELISA or immunohistochemistry and for transmission electron microscopy studies. Results: TKO mice developed qualitative disruptions in outer retinal layers in OCT by 3 months, increased accumulation of fundus spots and subretinal microglia by 6 months of age, significant retinal thinning by 9 months, and decreased ERG signal by 12 months. Furthermore, we found increased accumulation of the oxidative marker malondialdehyde (MDA) in the retina and increased basal laminal deposits (BLD) and mitochondria number and size in the retinal pigment epithelium of aging TKO mice. Conclusions: TKO mice can serve as a platform to study retinal diseases that involve chronic oxidative stress, including macular degeneration, retinal detachment, and ischemic retinopathies. In order to model each of these diseases, additional disease-specific catalysts or triggers could be superimposed onto the TKO mice. Such studies could provide better insight into disease mechanisms and perhaps lead to new therapeutic approaches.

Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial.

Importance: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. Objective: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks' gestational age. Design, Setting, and Participants: Randomized clinical trial included 638 infants younger than 28 weeks' gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. Interventions: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. Main Outcomes and Measures: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. Results: Among 638 infants (mean, 26 weeks' gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks' postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). Conclusions and Relevance: Among premature infants younger than 28 weeks' gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

ACCIDENTAL DUPLICATION: Colorado-Retinopathy of Prematurity (CO-ROP) Screening Algorithm: a validation study at a tertiary care center.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jaapos.2017.03.009. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Regulation of intraocular pressure by microRNA cluster miR-143/145.

Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye. Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.

Colorado Retinopathy of Prematurity Screening Algorithm (CO-ROP): a validation study at a tertiary care center.

PURPOSE: The Colorado Retinopathy of Prematurity Screening Algorithm (CO-ROP) recommends screening for infants meeting the following criteria for retinopathy of prematurity (ROP): gestational age ≤30 weeks, birth weight of ≤1500 g, and net weight gain of ≤650 g between birth and 4 weeks of age. This study was performed to evaluate the validity of CO-ROP in a tertiary referral county hospital. METHODS: CO-ROP was used to retrospectively analyze the data from consecutive newborns screened for ROP using national screening guidelines at Parkland Hospital, Dallas, Texas, between April 1, 2009, to August 30, 2013. Sensitivities and specificities for identifying ROP were calculated. RESULTS: A total of 374 infants were included, of whom 29 (7.8%) developed type 1 ROP and 12 (3.2%) developed type 2 ROP. The CO-ROP model would have decreased number of infants screened by 34% compared to current national screening criteria. CO-ROP had sensitivity of 93.1% (95% CI, 77.2-99.1) and 92.7% (95% CI, 61.5-99.8) for identifying type 1 and type 2 ROP, respectively. Of 29 patients who developed type 1 ROP, 2 were not identified using CO-ROP. CONCLUSIONS: The CO-ROP model significantly reduced total number screened but failed to detect 2 infants with type 1 ROP, suggesting the need for further modification of the algorithm.

A 10-year review of pediatric uveitis at a Hispanic-dominated tertiary pediatric ophthalmic clinic.

PURPOSE: The aim of this study was to evaluate the characteristics and outcomes of pediatric uveitis cases at a large tertiary referral center in Dallas, TX, USA. MATERIALS AND METHODS: The authors performed a retrospective chart review between 2001 and 2011 to identify children with uveitis. RESULTS: A total of 46 children (68 eyes) with uveitis were identified. Sixty-seven percent were Hispanic, and the mean age was 9.2 years. The majority of cases were idiopathic (74%). Anterior uveitis accounted for 42% of cases followed by intermediate uveitis/pars planitis (33%), posterior uveitis/retinitis (7%), and panuveitis (20%). Most patients were treated with corticosteroids (98% topical), 52% with systemic immunosuppression therapy, and 30% with surgery. Complications occurred in 74% of patients, with the most common complication being cataract development (26%), followed by posterior synechiae (24%). Twenty-four percent of patients had recurrences. Hispanic patients had worse visual acuities at presentation (P-value =0.073) and follow-up (P-value =0.057), compared to non-Hispanic patients. CONCLUSION: Pediatric uveitis cases seen in a large center in Dallas were largely idiopathic, had commonly developed complications, and were associated with worse visual outcomes in Hispanic patients.

Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo.

PURPOSE: Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. METHODS: Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. RESULTS: We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. CONCLUSIONS: We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.

A chimeric Cfh transgene leads to increased retinal oxidative stress, inflammation, and accumulation of activated subretinal microglia in mice.

PURPOSE: Variants of complement factor H (Cfh) affecting short consensus repeats (SCRs) 6 to 8 increase the risk of age-related macular degeneration. Our aim was to explore the effect of expressing a Cfh variant on the in vivo susceptibility of the retina and RPE to oxidative stress and inflammation, using chimeric Cfh transgenic mice (chCfhTg). METHODS: The chCfhTg and age-matched C57BL/6J (B6) mice were subjected to oxidative stress by either normal aging, or by exposure to a combination of oral hydroquinone (0.8% HQ) and increased light. Eyes were collected for immunohistochemistry of RPE-choroid flat mounts and of retinal sections, ELISA, electron microscopy, and RPE/microglia gene expression analysis. RESULTS: Aging mice to 2 years led to an increased accumulation of basal laminar deposits, subretinal microglia/macrophages (MG/MΦ) staining for CD16 and for malondialdehyde (MDA), and MDA-modified proteins in the retina in chCfhTg compared to B6 mice. The chCfhTg mice maintained on HQ diet and increased light showed greater deposition of basal laminar deposits, more accumulation of fundus spots suggestive of MG/MΦ, and increased deposition of C3d in the sub-RPE space, compared to controls. In addition, chCfhTg mice demonstrated upregulation of NLRP3, IP-10, CD68, and TREM-2 in the RNA isolates from RPE/MG/MΦ. CONCLUSIONS: Expression of a Cfh transgene introducing a variant in SCRs 6 to 8 was sufficient to lead to increased retinal/RPE susceptibility to oxidative stress, a proinflammatory MG/MΦ phenotype, and a proinflammatory RPE/MG/MΦ gene expression profile in a transgenic mouse model. Our data suggest that altered interactions of Cfh with MDA-modified proteins may be relevant in explaining the effects of the Cfh variant.

Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis.

PURPOSE: To report our experience using Ozurdex (Allergan, Irvine, CA), a biodegradable intravitreal implant containing of 0.7 mg of dexamethasone approved for use in adults with noninfectious uveitis in adults, in the treatment of pediatric uveitis. METHODS: The medical records of consecutive patients with noninfectious posterior uveitis who were unresponsive to standard treatment and subsequently received the Ozurdex implant from March 2011 to March 2013 were retrospectively reviewed. RESULTS: A total of 14 eyes of 11 patients (mean age, 10.1 years; range 4-12) received 22 Ozurdex implants during the study period. Of the 11 patients, 7 had idiopathic intermediate or posterior uveitis, 1 had sympathetic ophthalmia, 2 had juvenile idiopathic arthritis, and 1 had sarcoidosis. All patients were uncontrolled with standard treatment, including topical or sub-Tenon's or systemic corticosteriods and/or immune-modulation. Visual acuity improved after Ozurdex implant in 5 of 8 patients (63%). Intraocular inflammation was controlled or improved after 17 of 22 of implants (12 eyes [77%]). The frequency of topical corticosteroids was decreased and/or discontinued after 18 of 22 implants (12 eyes [82%]). Complications included implant migration into the anterior chamber (4 aphakic eyes), increased intraocular pressure (5 eyes), and progression of a preexisting cataract (1 eye). The uveitis reoccurred in 57% of eyes at 4.3 months (2-7 months) after injection. CONCLUSIONS: The Ozurdex implant in combination with systemic immunomodulatory therapy resulted in improved visual acuity, control of intraocular inflammation, and a decrease in corticosteroid use. In the majority of eyes the uveitis reoccurred around 4 months after injection. The adverse events in our study are similar to those identified in adult studies.