Publications by authors named "Quan Dong Nguyen"

255 Publications

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Ophthalmology 2021 Apr 14. Epub 2021 Apr 14.

Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2021.03.027DOI Listing
April 2021

Amine oxidase copper-containing 3 (AOC3) inhibition: a potential novel target for the management of diabetic retinopathy.

Int J Retina Vitreous 2021 Apr 12;7(1):30. Epub 2021 Apr 12.

Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Background: Diabetic retinopathy (DR), a microvascular complication of diabetes, is the leading cause of visual impairment in people aged 20-65 years and can go undetected until vision is irreversibly lost. There is a need for treatments for non-proliferative diabetic retinopathy (NPDR) which, in comparison with current intravitreal (IVT) injections, offer an improved risk-benefit ratio and are suitable for the treatment of early stages of disease, during which there is no major visual impairment. Efficacious systemic therapy for NPDR, including oral treatment, would be an important and convenient therapeutic approach for patients and physicians and would reduce treatment burden. In this article, we review the rationale for the investigation of amine oxidase copper-containing 3 (AOC3), also known as semicarbazide-sensitive amine oxidase and vascular adhesion protein 1 (VAP1), as a novel target for the early treatment of moderate to severe NPDR. AOC3 is a membrane-bound adhesion protein that facilitates the binding of leukocytes to the retinal endothelium. Adherent leukocytes reduce blood flow and in turn rupture blood vessels, leading to ischemia and edema. AOC3 inhibition reduces leukocyte recruitment and is predicted to decrease the production of reactive oxygen species, thereby correcting the underlying hypoxia, ischemia, and edema seen in DR, as well as improving vascular function.

Conclusion: There is substantial unmet need for convenient, non-invasive treatments targeting moderately severe and severe NPDR to reduce progression and preserve vision. The existing pharmacotherapies (IVT corticosteroids and IVT anti-vascular endothelial growth factor-A) target inflammation and angiogenesis, respectively. Unlike these treatments, AOC3 inhibition is predicted to address the underlying hypoxia and ischemia seen in DR. AOC3 inhibitors represent a promising therapeutic strategy for treating patients with DR and could offer greater choice and reduce treatment burden, with the potential to improve patient compliance.
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http://dx.doi.org/10.1186/s40942-021-00288-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042903PMC
April 2021

Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations.

J Ophthalmic Inflamm Infect 2021 Apr 9;11(1):11. Epub 2021 Apr 9.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University, 2370 Watson Court, Suite 200, Palo Alto, CA, 94303, USA.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.
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http://dx.doi.org/10.1186/s12348-021-00240-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032459PMC
April 2021

Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study.

Acta Ophthalmol 2021 Mar 9. Epub 2021 Mar 9.

Massachusetts Eye Research & Surgery Institution (MERSI), Waltham, MA, USA.

Purpose: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases.

Methods: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree).

Results: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent.

Conclusions: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.
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http://dx.doi.org/10.1111/aos.14702DOI Listing
March 2021

Bilateral preretinal hemorrhage associated with Kikuchi-Fujimoto disease.

Am J Ophthalmol Case Rep 2021 Jun 2;22:101041. Epub 2021 Mar 2.

Retina Institute of The Carolina and Macular Degeneration Center, Charlotte, NC, USA.

Purpose: To present a case of a patient with human immunodeficiency virus (HIV) disease and Kikuchi-Fujimoto disease (KFD) who presented with a unique pattern of retinopathy.

Observations: A 7-year-old Taiwanese girl with HIV disease who was recently diagnosed with KFD had a sudden onset of blurry vision in both eyes one month after her KFD systemic symptoms had relatively resolved. Ophthalmic examination showed decreased visual acuity in both eyes (OU). On fundus examination, she had bilateral preretinal, subhyaloid, and vitreous hemorrhage that was more severe than anemic retinopathy.

Conclusion: Ocular manifestations in Kikuchi-Fujimoto disease are rare; however, if they occur, presentations may vary. The exact etiology of the disease has remained elusive and controversial. This case is the first report of a patient with HIV disease and KFD presenting with ocular involvement. Furthermore, bilateral preretinal, subhyaloid, and vitreous hemorrhage, which was beyond anemic retinopathy, is an unprecedented manifestation of KFD that has not been previously reported. This case highlights the necessity for clinicians to consider all possible differential diagnoses when evaluating patients with similar findings to identify the best therapeutic approach and avoid unnecessary treatment.
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http://dx.doi.org/10.1016/j.ajoc.2021.101041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940994PMC
June 2021

Reperfusion of retinal ischemia in retinal occlusive vasculitis with nicotinic acid and infliximab in Adamantiades-Behçet's disease.

Am J Ophthalmol Case Rep 2021 Mar 5;21:101027. Epub 2021 Feb 5.

Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

To describe a case of ischemic retinal vasculitis in Adamantiades-Behçet disease (ABD) that demonstrated significant resolution of retinal ischemia following treatment with nicotinic acid and infliximab.: A 12-year-old male with a history of recurrent oral ulcers, fevers, and failure to thrive was admitted to the hospital with fever, oral and perirectal mucositis, and poor oral intake one month before presentation to uveitis clinic. He was suspected to have ABD and was treated with three doses of intravenous (IV) methylprednisolone (30 mg/kg/day) which led to improvement in his systemic symptoms. One week after admission, he complained of decreased vision in both eyes (OU), during which he was found to have anterior uveitis in OU and was referred to the Uveitis Clinic. Upon examination, his visual acuity was 20/80 in OU. Intraocular pressures were within normal limits. Anterior chamber evaluation revealed 0.5+ cells and 1.5+ flare in OU. Posterior examination revealed pale optic nerve, sclerosis and vascular sheathing of retinal arteries, and collateral vessels in OU. Fluorescein angiography (FA) showed optic disc leakage and widespread retinal ischemia in OU. The patient was diagnosed with retinal occlusive vasculitis associated with ABD. He was initially treated with infliximab (5 mg/kg), systemic methylprednisolone, and mycophenolate mofetil. Three months later, his BCVA improved to 20/70 OU with slight improvement of retinal ischemia on FA. Nicotinic acid was added to his treatment regimen. Due to logistic challenges, he did not receive infliximab treatment during the subsequent three months. However, three months after beginning nicotinic acid therapy, FA revealed significant improvement of his retinal ischemia OU. To our knowledge, the index report is the first to show that nicotinic acid may improve retinal ischemia in vaso-occlusive retinal vasculitis and be an integral part of the treatment regimen of this sight-threatening condition.
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http://dx.doi.org/10.1016/j.ajoc.2021.101027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878990PMC
March 2021

Brolucizumab-foreseeable workflow in the current scenario.

Eye (Lond) 2021 Feb 2. Epub 2021 Feb 2.

Byers Eye Institute, Stanford University, Palo Alto, Stanford, CA, USA.

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http://dx.doi.org/10.1038/s41433-020-01324-wDOI Listing
February 2021

Risk of Blindness Among Patients With Diabetes and Newly Diagnosed Diabetic Retinopathy.

Diabetes Care 2021 Mar 20;44(3):748-756. Epub 2021 Jan 20.

Genentech, Inc., South San Francisco, CA.

Objective: To evaluate the association between initial diabetic retinopathy (DR) severity/risk of blindness in patients with newly diagnosed DR/good vision in the U.S.

Research Design And Methods: This retrospective cohort study evaluated adult patients with good vision (20/40 or better) and newly diagnosed DR between 1 January 2013 and 31 December 2017 (index date) in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS) Registry. The primary exposure of interest was DR severity at index: mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). The main outcome measure was development of sustained blindness (SB), defined as study eyes with Snellen visual acuity readings of 20/200 or worse at two separate visits ≥3 months apart that did not improve beyond 20/100.

Results: Among 53,535 eligible eyes (mean follow-up 662.5 days), 678 (1.3%) eyes developed SB. Eyes with PDR at index represented 10.5% (5,629 of 53,535) of the analysis population but made up 26.5% (180 of 678) of eyes that developed SB. Kaplan-Meier analysis revealed that eyes with moderate NPDR, severe NPDR, and PDR at index were 2.6, 3.6, and 4.0 times more likely, respectively, to develop SB after 2 years of DR diagnosis versus eyes with mild DR at index. In a Cox proportional hazards model adjusted for index characteristics/development of ocular conditions during follow-up, eyes with PDR had an increased risk of developing SB versus eyes with mild NPDR at index (hazard ratio 2.26 [95% CI 2.09-2.45]).

Conclusions: In this longitudinal ophthalmologic registry population involving eyes with good vision, more advanced DR at first diagnosis was a significant risk factor for developing SB.
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http://dx.doi.org/10.2337/dc20-0413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896265PMC
March 2021

Tocilizumab for the Treatment of Ocular Inflammatory Disease.

Ocul Immunol Inflamm 2021 Jan 12;29(1):2-5. Epub 2021 Jan 12.

Centre for Ophthalmology, University Tuebingen, Tuebingen, Germany.

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http://dx.doi.org/10.1080/09273948.2020.1859257DOI Listing
January 2021

Preventing relapse in non-infectious uveitis affecting the posterior segment of the eye - evaluating the 0.2 μg/day fluocinolone acetonide intravitreal implant (ILUVIEN).

J Ophthalmic Inflamm Infect 2020 Nov 30;10(1):32. Epub 2020 Nov 30.

Moorfields Eye Hospital, London, UK.

Background: The current article is a short review of an Alimera Sciences-sponsored symposium held during The 15th International Ocular Inflammation Society Congress in Taiwan on the 14th November 2019 entitled, 'Preventing relapse of non-infectious uveitis effecting the posterior segment of the eye - evaluating the 0.2 μg/day fluocinolone acetonide intravitreal implant.'

Main Text: The fluocinolone acetonide intravitreal implant was approved in Europe for the prevention of relapse in recurrent non-infectious uveitis affecting the posterior segment of the eye and offers a systemic therapy-sparing treatment option by providing low daily dose of corticosteroid into the vitreous for up to 3 years. In the symposium, the presenters reported clinical outcomes from patients with non-infectious uveitis effecting the posterior segment of the eye to support the effectiveness and safety of the implant for up to 3 years in both randomised controlled trials and real-world practices.

Conclusions: Data showed that over a 36 month period, treatment with the fluocinolone acetonide intravitreal implant was associated with significantly fewer episodes of uveitic recurrence, a significantly longer time to uveitic recurrence, greater improvement in visual acuity, a lower need for adjunctive therapy, and an acceptable safety profile.
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http://dx.doi.org/10.1186/s12348-020-00225-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701203PMC
November 2020

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 447 Patients with Tubercular Intermediate Uveitis and Panuveitis.

Ocul Immunol Inflamm 2020 Nov 17:1-11. Epub 2020 Nov 17.

Northwestern University, Feinberg School of Medicine, Department of Ophthalmology , Chicago, Illinois, USA.

Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP. Multicentre retrospective analysis. A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n = 382/447; 85.4%) and 382 received corticosteroids (n = 382/447; 85.4%). Treatment failure was observed in 78 individuals (n = 78/447; 17.4%), occurring less frequently in patients receiving ATT (n = 66/382; 17.2%) compared to those who did not (n = 12/65; 18.5%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP. Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP.
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http://dx.doi.org/10.1080/09273948.2020.1808226DOI Listing
November 2020

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

Ophthalmology 2020 Nov 3. Epub 2020 Nov 3.

Departments of Ophthalmology and Medicine, Oregon Health & Science University and Legacy Devers Eye Institute, Portland, Oregon.

Purpose: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.

Design: Open-label, multicenter, phase 3 extension study (VISUAL III).

Participants: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis).

Methods: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose.

Main Outcome Measures: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids.

Results: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively.

Conclusions: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.
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http://dx.doi.org/10.1016/j.ophtha.2020.10.036DOI Listing
November 2020

How Do We Manage HLA-B27-associated Ocular Inflammation Refractory or Intolerant to Conventional Immunomodulatory Therapy?

J Ophthalmic Vis Res 2020 Oct-Dec;15(4):442-445. Epub 2020 Oct 25.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, California, USA.

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http://dx.doi.org/10.18502/jovr.v15i4.7777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591831PMC
October 2020

Cyclodialysis cleft repair with scleral band-buckle encirclage without cryopexy in the management of traumatic hypotony maculopathy.

Am J Ophthalmol Case Rep 2020 Dec 29;20:100946. Epub 2020 Sep 29.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To describe the technique of traumatic cyclodialysis cleft repair in the management of hypotony maculopathy using anterior placement of encircling scleral band-buckle.

Observations: A 51-year-old male who had sustained blunt trauma in the left eye two months prior to presentation in the clinics, presented with visual acuity of 20/200, a persistent cyclodialysis cleft with hypotony maculopathy and intraocular pressure (IOP) of 6 mm Hg. A silicone band-buckle was passed 360°; with its anterior edge hugging the insertion of rectus muscles along the 'spiral of Tillaux'. Post-operative course showed closure of the cleft with an IOP of 20 mm Hg at day 4. Patient underwent cataract extraction with intraocular lens implantation at two months and improved to 20/40 at the last follow up visit with a normal IOP.

Conclusion And Importance: We successfully managed a case of hypotony maculopathy due to persistent cyclodialysis cleft using a circumferential band buckle. We avoided the use of cryopexy to avoid the potential risk of inflammation - further worsening choroidal effusion and rare occurrence of suprachoroidal hemorrhage.
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http://dx.doi.org/10.1016/j.ajoc.2020.100946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557968PMC
December 2020

The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye.

Int J Retina Vitreous 2020 13;6:48. Epub 2020 Oct 13.

AsclepiX Therapeutics, Baltimore, MD USA.

Background: Retinal vascular diseases such as neovascular age-related macular degeneration, diabetic retinopathy and/or diabetic macular edema, and retinal vein occlusion with macular edema-share several key pathophysiologic aspects including neovascularization, vascular permeability, and inflammation. The role of vascular endothelial growth factor (VEGF) in these processes, and the therapeutic benefits of VEGF inhibition, have been well characterized. Anti-VEGF therapy is highly effective for many patients but is not uniformly effective in all patients and imposes a significant treatment burden. More recently, the role of the Tie2 signaling pathway in the pathophysiology of retinal vascular diseases has been investigated, and the Tie2 pathway represents a novel therapeutic target for these conditions.

Areas Covered: The index review describes the Tie2 pathway and its complementary role to the VEGF pathway in the angiogenesis cascade and will summarize studies of molecules in development to therapeutically modulate the Tie2 pathway in retinal vascular diseases.

Conclusions: Activation of the Tie2 pathway leads to downstream signaling that promotes vascular health and stability and decreases vascular permeability and inflammation. AXT107 is a collagen IV-derived synthetic peptide with a dual mechanism of action that involves suppression of VEGF signaling and activation of the Tie2 pathway; these actions are accomplished by AXT107 binding to and disrupting different integrin, leading to blockade of the VEGF receptor and rearrangement of cellular Tie2 rendering it susceptible to Ang2 agonism. Other Tie2 agonist compounds are also in development, including faricimab and razuprotafib. Tie2 activation only modestly impacts angiogenesis on its own but significantly potentiates VEGF suppression. Co-regulation of the VEGF and Tie2 signaling pathways has the potential to improve functional and structural outcomes in eyes with retinal vascular diseases.
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http://dx.doi.org/10.1186/s40942-020-00250-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557096PMC
October 2020

Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study.

Int J Retina Vitreous 2020 6;6:47. Epub 2020 Oct 6.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University, 2370 Watson Court, Suite 200, Palo Alto, CA 94303 USA.

Background: Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system.

Methods: STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6.

Results: 37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351).

Conclusions: IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.ClinicalTrials.gov Identifier: NCT01717170.
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http://dx.doi.org/10.1186/s40942-020-00245-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539516PMC
October 2020

Correlation between Subfoveal Choroidal Thickness and Anterior Segment Inflammation in Patients with Chronic Stage of Vogt-Koyanagi-Harada Disease.

Ocul Immunol Inflamm 2020 Oct 6:1-6. Epub 2020 Oct 6.

Department of Ophthalmology, Hospital Universitario Austral , Buenos Aires, Argentina.

Purpose: To correlate changes in subfoveal choroidal thickness (SCT) with the degree of anterior inflammatory activity in chronic Vogt-Koyanagi-Harada (VKH) disease.

Methods: Anterior segment inflammation was assessed using SUN anterior chamber cell grading criteria, and SCT was measured using EDI-OCT in patients with VKH at multiple visits. ANOVA was used to compare the mean SCT for each anterior chamber cell grade. Regression analysis was used to correlate the anterior segment cell grade and the SCT.

Results: 14 patients were included in the study. A total of 432 data points consisting of SCT and anterior segment cell values were analyzed. ANOVA demonstrated significant difference between the mean SCT for different anterior chamber cell grades ( < .0001). Regression analysis demonstrated significant correlation between SCT and grade of anterior chamber cells (R = 0.37, < .001).

Conclusions: Chronic VKH is characterized by a dynamic change in SCT that correlates with anterior segment inflammatory activity.
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http://dx.doi.org/10.1080/09273948.2020.1826533DOI Listing
October 2020

Impending central retinal vein occlusion in patient with idiopathic cutaneous leukocytoclastic vasculitis.

Am J Ophthalmol Case Rep 2020 Dec 18;20:100934. Epub 2020 Sep 18.

Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To report a case of impending central retinal vein occlusion (CRVO) associated with idiopathic cutaneous leukocytoclastic vasculitis (LCV) that demonstrated significant resolution following treatment with intravenous (IV) methylprednisolone.

Observations: A 27-year-old man presented to a tertiary Uveitis Clinic with a five-day history of blurry vision in the right eye (OD). He had a history of a purpuric rash and arthralgias five years ago and a biopsy-confirmed diagnosis of LCV controlled with colchicine two years ago in India. Recently, he presented with a recurrent rash and severe abdominal pain. After being evaluated by rheumatology and gastroenterology, he was placed on treatment and high dose oral prednisone, which improved his skin and gastrointestinal symptoms. At the first ophthalmic exam, his systemic findings included lower extremity purpura. His best-corrected visual acuity (BCVA) was 20/20 in both eyes (OU). Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed mild enlarged, tortuous veins, optic nerve hemorrhage, and intraretinal hemorrhages temporal to the macula in OD. Spectral-domain optical coherence tomography (SD-OCT) demonstrated multiple hyper-reflective, plaque-like lesions involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). The patient was diagnosed with impending central retinal vein occlusion (CRVO) in OD. Laboratory evaluations were unremarkable. Aspirin was initially started for the patient but was later held due to the worsening of retinal hemorrhage and retinal vein tortuosity at the one-week follow-up. The patient then received three doses of intravenous methylprednisolone, followed by systemic oral prednisone and mycophenolate mofetil. One month later, retinal hemorrhages, venous stasis, and skin manifestations resolved.

Conclusion And Importance: Ocular involvement in LCV is rare and may present with different manifestations. The index case is the first report of impending CRVO in a patient with idiopathic LCV and without any other known risk factors for CRVO. Our report not only describes the unique course of LCV-related ocular involvement, but also introduces and underscores a potentially effective therapeutic plan.
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http://dx.doi.org/10.1016/j.ajoc.2020.100934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522751PMC
December 2020

Imaging in Tubercular Choroiditis: Current Concepts.

Ocul Immunol Inflamm 2020 Nov 25;28(8):1223-1238. Epub 2020 Sep 25.

Advanced Eye Center, Post Graduate Institute of Medical Education and Research , Chandigarh, India.

Purpose: Ocular tuberculosis has protean clinical manifestations. Because of its varied clinical presentation, multimodal imaging is very important to characterize the disease activity, presence of inflammation, determining therapeutic response, and detection of complications.

Methods: Narrative review.

Results: In this review, various imaging modalities employed in the management of ocular tuberculosis including fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) have been reviewed. Not only do these imaging tools complement each other in providing a comprehensive assessment of the pathology, they also help in gaining valuable insights regarding the evolution of the disease.

Conclusions: Fundus imaging plays a vital role in the diagnosis and management of patients with posterior uveitis due to tuberculosis. Fundus imaging may have a useful role in defining clinical endpoints for ocular tuberculosis in the future.
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http://dx.doi.org/10.1080/09273948.2020.1817500DOI Listing
November 2020

Effect of Fundus Fluorescein Angiography on Semiautomated Aqueous Flare Measurements.

Ocul Immunol Inflamm 2020 Sep 23:1-4. Epub 2020 Sep 23.

Spencer Center for Vision Research, Byers Eye Institute, Stanford University , Palo Alto, California, USA.

Purpose: To evaluate the effects of fluorescein fundus angiography (FFA) on semiautomated aqueous flare measurements.

Methods: Laser flare photometer (LFP) measurements was performed at baseline, 30 min, and 4 h after the intravenous administration of sodium fluorescein dye. FFA was performed immediately after the baseline LFP measurement. LFP values at 30 min and 4 h after FFA were compared to baseline values. Mean change in LFP measurements at 30 min and 4 hafter baseline was compared between FFA arm and controls.

Results: The mean flare measurement in the FFA and control arm dropped 6% ( value = 0.002) and 9% ( value = 0.04), respectively. Mean change in LFP measurement at 30 min and 4 h after baseline was not significant between FFA arm and controls.

Conclusions: Administration of fluorescein dye does not increase LFP values. The decrease in the LFP measurement following FFA may be attributed to dilation drops.
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http://dx.doi.org/10.1080/09273948.2020.1799036DOI Listing
September 2020

Anti-interleukin-6 receptor therapy with tocilizumab for refractory pseudophakic cystoid macular edema.

Am J Ophthalmol Case Rep 2020 Dec 20;20:100881. Epub 2020 Aug 20.

Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To describe the clinical course of a patient with refractory pseudophakic cystoid macular edema treated with interleukin-6 receptor antagonist tocilizumab.

Observations: An 80-year-old Caucasian man with past ocular history significant for glaucoma (right eye) and iritis presented with cystoid macular edema (CME) in the right eye (OD). His ocular surgery history was significant for cataract extraction with posterior chamber intraocular lenses in 1999 and YAG laser capsulotomy in 2014 in both eyes (OU). His medications at time of presentation included latanoprost and dorzolamide-timolol in OD for glaucoma, as well as prednisolone in OD for iritis. Upon examination, his visual acuity was 20/250 in OD and 20/20 in the left eye (OS). Intraocular pressure was 20 mmHg in OD and 10 mmHg in OS. Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed CME and a cup-to-disk ratio of 0.9 in OD and normal findings in OS. Initial spectral domain optical coherence tomography (SD-OCT) demonstrated intraretinal fluid in both outer and inner layers as well as mild subretinal fluid with an intact ellipsoid zone in OD. Fluorescein angiography revealed perifoveal leakage in OD. Laboratory evaluations, including infectious work-up, were unremarkable. While the patient's CME initially improved after initiation of therapy with topical prednisolone and oral acetazolamide, the CME later recurred after systemic acetazolamide was stopped due to intolerable side effects. Despite multiple therapeutic approaches, including topical and systemic corticosteroids (both oral and intravenous) and topical interferon α2b over the course of more than one year, the patient's visual acuity continued to worsen with increasing intra- and subretinal fluid in the macula. Due to the refractory CME, the patient was started on monthly infusions of anti-interleukin (IL)-6 receptor tocilizumab (8 mg/kg) with three days of methylprednisolone infusions (500 mg/day). After nine cycles of treatment, SD-OCT demonstrated restoration of normal foveal contour with complete resolution of CME.

Conclusions And Importance: IL-6 inhibition with tocilizumab may be a safe and effective treatment for refractory CME. Further studies are needed to elucidate the nature and extent of therapeutic IL-6 inhibition in CME.
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http://dx.doi.org/10.1016/j.ajoc.2020.100881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452126PMC
December 2020

Systemic immunosuppressive therapies for uveitis in developing countries.

Indian J Ophthalmol 2020 Sep;68(9):1852-1862

L V Prasad Eye Institute, Hyderabad, Telangana, India.

There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment is corticosteroid therapy. Corticosteroids remain the most potent and efficacious drugs for treating intraocular inflammation. However, their long-term use is limited by their medium- and long-term side effects, which are a major concern. The approach taken to limit corticosteroid side effects is to introduce steroid-sparing agents that suppress the inflammatory pathways and immune response differently than corticosteroids. There are several classes of such drugs that are affordable, effective, and generally well-tolerated. Relatively recently, an increasing range of biologic agents has become available to treat intraocular inflammation. However, the relatively expensive cost of these therapies limits their use in the developing world. This systemic review aimst to discuss the use of corticosteroids and different immunosuppressive regimens in the management of various uveitides.
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http://dx.doi.org/10.4103/ijo.IJO_1548_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690522PMC
September 2020

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Descriptive Review of Tubercular Uveitis in Paediatric Population.

Ocul Immunol Inflamm 2020 Aug 17:1-7. Epub 2020 Aug 17.

Centre for Ophthalmic Specialised Care, University of Lausanne , Lausanne, Switzerland.

Purpose: To examine disease profile of tubercular uveitis (TBU) in Paediatric population.

Methods: Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1, 29 Paediatric patients diagnosed with TBU were analyzed.

Results: Mean age of disease presentation was 12.8 (range 4-18 years), with predominance of males (n = 14/20; 70.0%) and Asian ethnicity (n = 25/29; 86.2%). Posterior uveitis (n = 14/28; 50%) was the most frequent uveitis phenotype, with choroidal involvement occurring in 64.7% (n = 11/17). Incidence of optic disc edema and macular edema was higher in children (n = 8/18; 44.4% and n = 5/18; 27.8%, respectively) than in adults (n = 160/942; 16.9% and n = 135/942; 14.3%, respectively). Comparison of optic disc edema between subgroups showed a significant difference (). All patients received oral corticosteroids, most of them with antitubercular therapy. Treatment failure developed in 4.8% (n = 1/21).

Conclusions: Children have a more severe inflammatory response to the disease, and an intensive anti-inflammatory therapeutic regimen is required to achieve a positive treatment outcome.
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http://dx.doi.org/10.1080/09273948.2020.1781197DOI Listing
August 2020

[Evolving Consensus of International Uveitis Study Group, Intraocular Inflammation Society, and Foster Ocular Inflammation Society with Uveitis in the Time of COVID-19 Infection].

Klin Monbl Augenheilkd 2020 Sep 14;237(9):1124-1128. Epub 2020 Aug 14.

Ophthalmology, Singapore Eye Research Institute, Singapur.

This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS) and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic.
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http://dx.doi.org/10.1055/a-1201-3277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516354PMC
September 2020

Reply.

Ophthalmology 2020 11 29;127(11):e102-e103. Epub 2020 Jul 29.

Advanced Eye Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2020.06.005DOI Listing
November 2020

Evolving Consensus Experience of the IUSG-IOIS-FOIS with Uveitis in the Time of COVID-19 Infection.

Ocul Immunol Inflamm 2020 Jul;28(5):709-713

Department of Medical Retina and Uveitis, Moorfields Eye Hospital , London, UK.

This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS), and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic.
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http://dx.doi.org/10.1080/09273948.2020.1780273DOI Listing
July 2020

Yet another case of ocular sarcoidosis.

Am J Ophthalmol Case Rep 2020 Sep 11;19:100825. Epub 2020 Jul 11.

Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To report a case of bilateral pan-uveitis resembling fungal and viral endophthalmitis in a patient who was ultimately diagnosed with sarcoidosis.

Observation: A 64-year-old female presented with a four-day history of painless vision loss in the right eye. She presented with multiple concurrent systemic complaints, including a history of oral and genital sores, patches of hypopigmented skin on her forearms, and occasional shortness of breath. Upon further examination, she was noted to have bilateral pan-uveitis, which was more severe in the right than left eye. Posterior pole examination of the right eye revealed dense vitritis with multiple large whitish round balls that seemed suggestive of fungal or viral endophthalmitis. Initial therapies included intravitreal (IVT) foscarnet and intravenous (IV) acyclovir, followed by IV amphotericin B and oral voriconazole, which did not improve ocular signs and symptoms. Further evaluations ruled out infectious etiologies and lymphoma. Chest computerized tomography (CT) scan revealed findings suggestive of sarcoidosis, which was confirmed with lung biopsy. Anti-viral and -fungal treatments were discontinued, and the patient was started on IV methylprednisolone followed by oral prednisone and mycophenolate mofetil. Ocular symptoms improved, and the patient remained stable after treatment.

Conclusion And Importance: The index report illustrates a case of ocular sarcoidosis that imitated the presentation of infectious endophthalmitis. Though ocular sarcoidosis is known to masquerade as a range of disorders and constitutes part of the differential diagnosis for infectious endophthalmitis, sarcoidosis has not been reported in recent literature to imitate the presentation of fungal endophthalmitis. The index case suggests that ocular sarcoidosis should be considered in the differential diagnoses of fungal endophthalmitis.
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http://dx.doi.org/10.1016/j.ajoc.2020.100825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372148PMC
September 2020

Pharmacological agents in development for diabetic macular edema.

Int J Retina Vitreous 2020 8;6:29. Epub 2020 Jul 8.

Byers Eye Institute, Stanford University, Palo Alto, CA 94303 USA.

Background: Diabetic macular edema (DME) is the leading cause of visual loss in patients with diabetic retinopathy. There has been a paradigm shift in the treatment of DME since the advent of anti-vascular endothelial growth factor (anti-VEGF) therapy. The safety and efficacy of anti-VEGF therapy has been well established. Although efficacious, currently approved anti-VEGF agents are associated with certain limitations, which include, among others: frequent need for injections, high treatment cost and variable response to treatment. These challenges have led to an active search for more novel agents that may be able to overcome these limitations.

Areas Covered: The index review focuses on novel treatment agents that target various pathways in patients with DME. These agents are used either as monotherapy or in combination with other agents in the management of DME. Drugs discussed include novel anti-VEGF inhibitors, TIE-2 receptor modulators, integrin peptide inhibitors, rho kinase inhibitors, and future therapies such as neuroprotection and gene therapy.

Conclusions: The future of investigational pharmacological therapy appears promising for patients with DME. Results from early clinical trials indicate that newer agents highlighted in the study may be safe and efficacious treatment options for patients with DME. However, data from large multicenter clinical trials need to be analyzed before these agents can be incorporated into clinical practice.
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http://dx.doi.org/10.1186/s40942-020-00234-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341631PMC
July 2020

Obtaining undiluted vitreous sample using small gauge pars plana vitrectomy and air infusion.

Am J Ophthalmol Case Rep 2020 Sep 5;19:100768. Epub 2020 Jun 5.

Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Vitreous biopsy is essential for establishing a definitive diagnosis and guiding potential therapy in patients with refractory vitritis and posterior uveitis, among other indications. Especially in cases where one must rule out intraocular lymphoma, obtaining a significant amount of undiluted vitreous increases diagnostic yield. We demonstrate our technique for obtaining a significant amount of undiluted vitreous using pars plana vitrectomy with air infusion.
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http://dx.doi.org/10.1016/j.ajoc.2020.100768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327279PMC
September 2020