Search

Ploysai Rujkorakarn,1– 3 Michael J Margolis,1,2 Diana Morvey,1,2 Yujia Zhou,1,2 C Stephen Foster1,2,4 1Massachusetts Eye Research and Surgery Institution, Waltham, MA, USA; 2The Ocular Immunology and Uveitis Foundation, Waltham, MA, USA; 3Suddhavej Hospital Department of Ophthalmology, Mahasarakham University, Maha Sarakham, Thailand; 4Department of Ophthalmology, Harvard Medical School, Cambridge, MA, USACorrespondence: C Stephen Foster, Massachusetts Eye Research and Surgery Institution, 1440 Main St. #201, Waltham, MA, 02451, USA, Tel +1 781 891-6377, Fax +1 781 647-1430, Email sfoster@mersi.comPurpose: To assess the possible correlation of anti-retinal antibody titers and number of anti-retinal antibodies with outcome measurements including visual acuity, subjective vision loss, visual field, and electroretinography in patients with autoimmune retinopathy.Design: Single-center, retrospective cross-sectional study.Patients and Methods: Patients with autoimmune retinopathy who underwent anti-retinal antibody testing at least twice during their follow-up were enrolled. Anti-retinal antibody titers and numbers were grouped as improved, stable, or worsened. Outcomes included Snellen visual acuity, patient-reported vision loss, Humphrey visual field mean deviations, and electroretinography parameters.Results: Thirty-one eyes among 16 patients with autoimmune retinopathy were included. Between-group analyses of visual acuity, subjective vision loss, visual field, and electroretinography outcomes did not reveal any significant differences by anti-retinal antibody titer or number group at a 95% confidence interval.Conclusion: Changes in anti-retinal antibody titers or numbers were not associated with any vision outcome. Repeated anti-retinal antibody testing may be unnecessary after diagnosis of autoimmune retinopathy and detection of an anti-retinal antibody.Keywords: autoimmune retinopathy, anti-retinal antibody, visual field, electroretinography, outcome measurements

Objective: To evaluate the incidence of visually significant posterior capsule opacification (PCO with visual acuity ≤20/50) and the incidence of Nd:YAG laser capsulotomy in the year following cataract surgery for uveitic eyes., Method: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study using a standardized chart review process., Results: Among 1,855 uveitic eyes of 1,370 patients who had undergone cataract surgery, visually significant PCO occurred in 297 eyes (16%), and YAG laser capsulotomy was done in 407 eyes (22%) within the first year following surgery. Higher odds of developing 20/50 visual acuity attributed to PCO were noted in children and young adults compared with adults older than 65 years of age (overall p = 0.03). Poorer preoperative visual acuity (overall p = 0.0069) and postoperative inflammation (odds ratio [OR] = 1.83; 95% CI, 1.37-2.45; p < 0.0001) were associated with PCO incidence. In multivariable analysis, risk factors for YAG laser capsulotomy were younger age groups compared with those older than 65 years of age at the time of surgery (adjusted OR [aOR] = 1.90-2.24; 95% CI, 1.90-2.24; overall p = 0.0007), female sex (aOR = 1.37; 95% CI, 1.03-1.82; p = 0.03), postoperative active inflammation (aOR = 165; 95% CI, 1.27-2.16; overall p < 0.0001), extracapsular cataract extraction compared with phacoemulsification (aOR = 1.70; 95% CI, 1.17-2.47; overall p < 0.0001), and insertion of an intraocular lens (aOR = 4.60; 95% CI, -2.29-9.25; p < 0.0001). Black race was associated with lower YAG laser capsulotomy incidence than Whites (aOR = 0.36; 95% CI, 0.24-0.52; overall p < 0.0001)., Conclusions: Vision-reducing (≤20/50) PCO is common, occurring in about one sixth of uveitic eyes within 1 year of cataract surgery; a higher number (22%) of eyes underwent YAG laser capsulotomy within the first year. Age and postoperative inflammation following cataract surgery are the variables most associated with the incidence of visually significant PCO and YAG laser capsulotomy., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN)., Methods: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months., Results: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p  = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p  < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p  < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p  = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group ( p  = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi ., Conclusions: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

Purpose: To document a case involving a patient previously diagnosed with Behçet's disease which proved unresponsive to multiple immunomodulatory therapies, and was subsequently diagnosed with secondary cytomegalovirus retinitis and appropriately treated., Methods: This is a case report focused on the images., Results: A 39-year-old female, previously diagnosed with Behçet's disease unresponsive to multiple immunomodulatory therapies, sought a second opinion at our clinic due to more floaters and a scotoma in her left eye for a few months. Her right eye had become blind as a result of multiple glaucoma and vitreoretinal surgeries. Her best corrected visual acuity was 20/60 in the left eye. A Slit lam examination of the left eye showed 1+ cells and flare in the anterior chamber along with 1+ cells in the anterior vitreous with no vitreous haze. Dilated fundoscopy of the left eye reveled an atrophic lesion in the inferior macula. Fluorescein angiography demonstrated a mixed hypo- and hyperfluorescent lesion in the left eye. Optical coherence tomography macula demonstrated an atrophic lesion in the inferior macula of the left eye. All laboratory findings were predominantly negative or within the normal range, except for the presence of antibodies to VZV and CMV in the blood. Polymerase chain reaction analysis of the vitreous sample uncovered the presence of CMV, leading to appropriate curative and prophylactic treatment for the patient., Conclusions and Importance: In patients with resistant noninfectious uveitis, particularly those experiencing underlying disease reactivation, the possibility of infections, especially opportunistic ones, should be taken into consideration., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C. Stephen Foster declares the following: Consultancies with Aldeyra Therapeutics (Lexington, MA), Allakos (Redwood City, CA), Bausch & Lomb Surgical, Inc. (Rancho Cucamonga, CA), Eyegate Pharma (Waltham, MA), Genentech (South San Francisco, CA), Novartis (Cambridge, MA), and pSivida (Watertown, MA). Grants or grants pending with Aciont (Salt Lake City, UT), Alcon (Aliso Viejo, CA), Aldeyra Therapeutics (Lexington, MA), Bausch & Lomb (Rochester, NY), Clearside Biomedical (Alpharetta, GA), Dompé pharmaceutical (Milan, Italy), Eyegate Pharma (Waltham, MA), Mallinckrodt pharmaceuticals (Staines-upon-Thames, UK), Novartis Pharmaceuticals (Cambridge, MA), pSivida (Watertown, MA), and Santen (Osaka, Japan). Payment for lectures including service on speaking bureaus: Alcon (Aliso Viejo, CA), Allergan (Dublin, Ireland), Mallinckrodt pharmaceuticals (Staines-upon-Thames, UK). Stock or Stock Options: Eyegate Pharma (Waltham, MA). Arash Maleki has nothing to declare.

Introduction: Bilateral hemorrhagic hypopyon, also known as candy cane hypopyon, is an extremely rare presentation which we report as a unique case in association with intraocular mantle cell lymphoma (MCL)., Case Presentation: A 63-year-old white male presented with a 3-week history of conjunctival injection OS that was unresponsive to erythromycin ointment and topical steroids, in the setting of recently discovered diffuse lymphadenopathy and malaise. On presentation, he was found to have bilateral hemorrhagic hypopyon. Lymph node biopsy was diagnostic of MCL, and subsequent anterior chamber paracentesis confirmed intraocular MCL. The patient was put into remission with intravitreal rituximab injections, systemic chemotherapy, and external beam radiation., Conclusion: Cases of MCL with ocular involvement typically involve ocular adnexal structures, and seldom involve the uvea. Furthermore, this patient represents an extremely unusual case in his presentation with a hemorrhagic hypopyon., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To develop a novel grading scale for assessing conjunctival inflammation in cicatrizing conjunctivitis associated with Pemphigoid., Methods: We performed a retrospective analysis of digital slit-lamp images for patients with cicatricial pemphigoid in which best-quality conjunctival images for each eyelid at each photographic session was selected and anonymized. These images were subsequently prospectively assessed for inflammation severity on a scale of 0-4+ by a fellowship-trained ophthalmologist specializing in pemphigoid. The most representative image grade of inflammation was then compiled to create a visual composite, accompanied by corresponding verbal descriptions for each level of inflammation. The primary outcome measure was the development of a novel 4-point grading scale demonstrating progressive degrees of conjunctival inflammation in patients with cicatrizing conjunctivitis associated with pemphigoid., Results: A total of 6,969 conjunctival images from 113 patients with cicatrizing conjunctivitis secondary to pemphigoid were reviewed and narrowed to 452 images, each representing the best single clarity image from each eyelid per photo session. The images were then sorted into five groups by degree of inflammation (0-4+). The most representative photographs of the upper and lower eyelids in each group were then selected to create a visual composite with an associated verbal descriptor for each level of inflammation., Conclusion: A novel 4-point grading scale was developed incorporating both verbal descriptors and visual components to quantify conjunctival inflammation in patients with cicatrizing conjunctivitis associated with Pemphigoid.

Purpose: To report a case of Cogan-Like Syndrome following treatment with nivolumab for metastatic cutaneous melanoma., Methods: A case report., Results: A 54-year-old female sought a second opinion from us regarding the recently diagnosed uveitis in both eyes. She had a diagnosis of metastatic cutaneous melanoma in the right arm and was undergoing treatment with nivolumab. Four weeks following the initiation of nivolumab therapy, she experienced tinnitus and bilateral sensorineural hearing loss, which was treated with oral and intratympanic steroids. While tapering the oral steroids, she developed iridocyclitis with papillitis in both eyes. This combination of vestibuloauditory symptoms and ocular inflammation was strikingly reminiscent of Cogan's syndrome. Because of the timing in relation to the nivolumab therapy and the steroid responsiveness of her presentation, this was speculated to be due to immune overactivation from the nivolumab. Given her complex condition, which involved toxicity and multiple metastases, the patient was advised to consider either topical and/or local corticosteroids or intravenous immunoglobulin. The patient chose to persist with corticosteroid therapy., Conclusion: Nivolumab could potentially be linked to an immune-related condition resembling Cogan syndrome. In cases involving patients with a complex condition necessitating nivolumab treatment, the use of topical and/or local corticosteroids or intravenous immunoglobulin, might constitute the sole viable treatment options.

Background: Behcet disease is a systemic vasculitis, which may involve the eyes and central nervous system. The true prevalence of neurological involvement is not precisely known but may be associated with ocular involvement. This study investigates the association between Behcet uveitis and neuro-Behcet disease., Methods: A retrospective single-center analysis was conducted for consecutive patients with Behcet uveitis at the Massachusetts Eye Research and Surgery Institution. Uveitis characteristics, neurological symptoms, fluorescein fundus angiography, and MRI results were recorded., Results: Our population included 108 patients with Behcet uveitis, and 26 (24.1%) were found to have neurological involvement associated with Behcet disease. Optic nerve leakage on fundus angiography and neurological symptoms were associated with an increased risk of neurological involvement. Three cases (11.5%) were nonparenchymal, while 23 (88.5%) were parenchymal with lesions in the cortex, subcortical white matter, thalamus, basal ganglia, and brainstem., Conclusions: There is a high comorbidity between ocular and neurological involvement in Behcet disease. Careful assessment of neurological symptoms and baseline fluorescein fundus angiography are recommended for patients with Behcet disease. MRI has a high diagnostic yield and should be pursued if there is concern for progressive or pre-existing neurological involvement., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Purpose: The aim of this study was to investigate the prevalence of IgM along the basement membrane zone (BMZ) of patients with ocular cicatricial pemphigoid (OCP) and the outcomes of these patients with immunomodulatory therapy., Methods: This study is a retrospective chart review of patients with conjunctival biopsy-proven OCP. Clinical data, including the presence of linear IgM deposition along the BMZ on either direct immunofluorescence or avidin-biotin complex immunohistochemistry, were recorded. Response to IMT was also recorded., Results: A total of 817 patients with documented conjunctival biopsies were identified, with 93 (11.4%) positive for OCP with linear IgM deposition along the BMZ. Forty-six patients with sufficient follow-up were evaluated for clinical outcomes, with 35 (76.1%) able to achieve durable remission an average of 24.3 months after initiation of IMT. Most of these patients, 82.9%, were able to achieve durable remission with first-line antimetabolite therapy. Three patients were identified with solely IgM-positive conjunctival biopsies., Conclusions: Our study suggests that IgM positivity is seen in a minority of patients with OCP and that outcomes are comparable for these patients to the general OCP patient population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Chronic anterior uveitis (CAU) often requires suppressive therapy, which has potential side effects including cataract, ocular hypertension, and increased risk of infection. No remittive therapy is currently available; however, several studies have demonstrated an association between low 25-hydroxy Vitamin D (25OHD) levels and either uveitis incidence or uveitis disease activity. This study investigates the potential of Vitamin D supplementation as a remittive treatment for CAU., Methods: We conducted a retrospective analysis using data from the Systemic Immunosuppressive Therapy for Eye Disease (SITE) cohort study, which included patients with ocular inflammatory disease seen at U.S. tertiary centers between 1979 and 2010. Vitamin D supplementation data was analyzed for patients with CAU. Eyes were considered in remission if they remained quiet for at least 90 days off all anti-inflammatory treatment for eye disease., Results: Among 2688 patients who never used Vitamin D, the cumulative adjusted CAU remission incidence was 13.5% at the 16-month follow-up. In contrast, among 75 patients who used Vitamin D for a duration of ≤1 year, the cumulative adjusted CAU remission incidence was 28% at 16 months. The use of Vitamin D was associated with a crude hazard ratio for remission of 2.14 [95% confidence interval (CI) 1.23-3.71, p  = 0.0071], and an adjusted hazard ratio for remission of 2.43 [95% CI: 1.36-4.33, p  = 0.0027]., Conclusion: In the SITE Cohort, Vitamin D supplementation is associated with a significantly increased incidence of remission. Vitamin D supplementation should be explored in a prospective trial as the next step of evaluation.

Purpose: To evaluate the incidence, remission, and relapse of post-surgical cystoid macular edema (PCME) following cataract surgery in inflammatory eye disease., Methods: A total of 1859 eyes that had no visually significant macular edema prior to cataract surgery while under tertiary uveitis management were included. Standardized retrospective chart review was used to gather clinical data. Univariable and multivariable logistic regression models with adjustment for inter-eye correlations were performed., Results: PCME causing VA 20/50 or worse was reported in 286 eyes (15%) within 6 months of surgery. Adults age 18-64 years as compared to children (adjusted odds ratio [aOR] = 2.42, for ages 18 to 44 years and aOR = 1.93 for ages 45 to 64 years, overall P = .02); concurrent use of systemic immunosuppression (conventional aOR 1.53 and biologics aOR = 2.68, overall P = .0095); preoperative VA 20/50 or worse (overall P < .0001); cataract surgery performed before 2000 (overall P = .03) and PMCE in fellow eye (aOR = 3.04, P = .0004) were associated with development of PCME within 6 months of cataract surgery. PCME resolution was seen in 81% of eyes at 12 months and 91% of eyes at 24 months. CME relapse was seen in 12% eyes at 12 months and 19% eyes at 24 months., Conclusions: PCME occurs frequently in uveitic eyes undergoing cataract surgery; however, most resolve within a year. CME recurrences likely are due to the underlying disease process and not relapses of PCME., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study outlines a scenario involving unilateral periocular inflammation exhibited resistance to conventional immunomodulatory therapy (IMT) and biologic response modifying agents, which was successfully managed with oral cyclophosphamide monotherapy. A 39-year-old male visited our clinic, expressing discomfort and swelling in his left upper eyelid for six months. All multidisciplinary consultations and imaging yielded normal results. He remained consistently on a dosage of 50 mg oral prednisone. Blood tests yielded results within the normal range or were negative, with the exception of the antinuclear antibody. He did not respond to conventional IMT and biological response modifier agents. Ultimately, the patient began oral cyclophosphamide. One month after commencing cyclophosphamide treatment, the oral prednisone dosage was gradually reduced without any flare-up. oral cyclophosphamide can serve as a valuable treatment for periocular inflammation that does not respond to standard conventional IMT and biologic response modifier agents., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Oman Ophthalmic Society.)

Buraa Kubaisi,1,2 Arash Maleki,1,2 Aseef Ahmed,1,2 Neel Lamba,1,2 Haitham Sahawneh,1,2 Andrew Stephenson,1,2 Alyssa Montieth,1,2 Shobha Topgi,3 C Stephen Foster1,2,4 1Massachusetts Eye Research and Surgery Institution, Waltham, MA, USA; 2Ocular Immunology & Uveitis Foundation, Waltham, MA, USA; 3The State University of New York Downstate, Brooklyn, NY, USA; 4Harvard Medical School, Boston, MA, USA Purpose: To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) in eyes with noninfectious uveitis that had fluocinolone acetonide intravitreal implant (Retisert™)-induced glaucoma. Methods: This retrospective study reviewed the safety and efficacy of AGV implantation in patients with persistently elevated intraocular pressure (IOP) after implantation of a fluocinolone acetonide intravitreal implant at the Massachusetts Eye Research and Surgery Institution between August 2006 and November 2015. Results: Nine patients with 10 uveitic eyes were included in this study, none of which had preexisting glaucoma in the study eye. Mean patient age was 42 years; 6 patients were female and 3 were male. Baseline mean IOP was 30.6 mmHg prior to AGV placement while mean IOP-lowering medications were 2.9. In the treatment groups, there was a statistically significant reduction in post-AGV IOP. IOP was lowest at 1-week after AGV implantation (9.0 mmHg). Nine out of 10 eyes achieved an IOP below target value of 22 mmHg and/or a 20% reduction in IOP from baseline 1 month and 1 year following AGV placement. All other postoperative time points showed all 10 eyes reaching this goal. A statistically significant decrease in IOP-lowering medication was seen at the 1-week, 1-month, and 3-year time points compared to baseline, while a statistically significant increase was seen at the 3-month, 6-month, and 2-year post-AGV time points. No significant change in retinal nerve thickness or visual field analysis was found. Conclusion: AGV is an effective and safe method of treatment in fluocinolone acetonide intravitreal implant-induced glaucoma. High survival rate is expected for at least 3 years. Keywords: uveitis, glaucoma, Ahmed glaucoma valve, fluocinolone acetonide intravitreal implant, ocular inflammation

Purpose: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP)., Methods: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded., Results: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up., Conclusions: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To determine the sensitivity and specificity of syphilis antibody tests in vitreous samples and to propose an algorithm using vitreous syphilis antibody as a supplementary test to confirm syphilitic uveitis (SU)., Methods: A prospective case-control study was conducted at the Retina and Uveitis Clinic from May 2017 to January 2020. Initially, patients were classified based on syphilis serology into group 1 (positive testing) and group 2 (negative testing). Group 1 was further divided into 2 subgroups (group 1A and 1B) depending on their relevant clinical manifestations and clinical improvement. Group 2 served as a control group., Results: Thirty-eight patients were enrolled in the study: 14 in group 1A, 5 in group 1B, and 19 in group 2B. No patient was assigned to group 2A. All patients in group 1A, representing definite SU, completed syphilis test (rapid plasma reagin [RPR], enzyme immunoassay [EIA], and fluorescent treponemal antibody-absorption [FTA-ABS]) for vitreous, and all vitreous samples yielded positive results. Of the 5 subjects in group 1B, 3 cases were considered to be not SU with different conditions, and 2 were indeterminate for SU. They presented with different features not typical of SU, and they had variable and fewer positive syphilis antibody responses. The most sensitive test for detecting syphilis antibodies in vitreous was EIA (90.9%), followed by RPR (80.0%) and FTA-ABS IgG (78.9%). EIA and FTA-ABS had the highest specificity, detecting 100% of the syphilis antibody., Conclusions: Vitreous analysis of syphilis antibody can serve as a supplementary test to confirm SU in selected cases as the proposed algorithm., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Arash Maleki,1,2 Neerav Lamba,1,2 Lina Ma,1,2 Stacey Lee,1,2 Alexander Schmidt,1,2 C Stephen Foster1–3 1Massachusetts Eye Research and Surgery Institution, 2Ocular Immunology and Uveitis Foundation, Waltham, 3Harvard Medical School, Boston, MA, USA Purpose: To examine the efficacy of rituximab as a monotherapy or in combination therapy for the treatment of patients with non-paraneoplastic autoimmune retinopathy. Methods: Twelve eyes of six patients with non-paraneoplastic autoimmune retinopathy who were treated with rituximab and had at least 6 months of follow-up were included. Demographic data, clinical data, visual field parameters, electroretinography parameters, and anti-retinal and anti-optic nerve autoantibody bands were collected from the Massachusetts Eye Research and Surgery Institution database between September 2010 and January 2015. Changes in visual acuity, visual field parameters, electroretinography parameters, and anti-retinal and anti-optic nerve autoantibody bands from the initial visit to the most recent visit were examined. Results: From the initial visit to the last visit, visual acuity was stable in eight (66.7%) eyes. Visual field was stable in six (50%) eyes and improved in two (16.7%) eyes. Electroretinography was stable or improved in eight (66.7%) eyes. The average number of anti-retinal and anti-optic nerve antibody bands was reduced. Conclusion: Stabilization and/or improvement of visual acuity, visual field parameters, and electroretinography parameters were observed in a high number of patients (75%) on rituximab, as a monotherapy (one patient) or in combination therapy. Keywords: birdshot retinochoroidopathy, bortezomib, CD20, cyclophosphamide, HLA-A29, HLA-B27, immunomodulatory therapy, systemic lupus erythematosus

Caiyun You,1–3 Haitham F Sahawneh,1,2 Lina Ma,1,2 Buraa Kubaisi,1,2 Alexander Schmidt,1,2 C Stephen Foster1,2,4 1Massachusetts Eye Research and Surgery Institution (MERSI), Waltham, 2Ocular Immunology and Uveitis Foundation, Weston, MA, USA; 3Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 4Harvard Medical School, Boston, MA, USA Introduction: Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation.Area covered: The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA).Our perspective: IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease. Keywords: immunomodulatory, orphan drug, steroid sparing, uveitis

Purpose: To evaluate outcomes of intravenous (IV) tocilizumab (TCZ) in patients with pars planitis refractory to conventional immunomodulatory therapy and anti-tumor necrosis factor (TNF) alpha agents., Methods: Medical records of eight patients diagnosed with pars planitis and treated with monthly 4 or 8 mg/kg IV TCZ were reviewed. The primary objective was to initiate and sustain remission continuously for three consecutive months. Secondary outcome measures were changes in best corrected visual acuity (BCVA), degree of anterior chamber (AC) inflammation, vitreous cell, vitreous haze, presence of vitreous or pars plana exudates, peripheral vasculitis, fluorescein angiography (FA) score and central subfieldthickness (CST) on macular optical coherence tomography (OCT)., Results: Fourteen eyes of eight patients were treated with IV TCZ. Seven patients were women. The average age was 31.35 ± 16.42 years. In 6 (75%) out of 8 patients, IV TCZ, either as monotherapy or in combination with another conventional immunomodulatory agent, induced and sustained remission. The average FA score reduced from 11.15 ± 3.52 at the baseline visit to 6.50 ± 2.12 at the one-year follow-up visit (p-value < 0.05). None of the patients experienced any side effects of IV TCZ., Conclusion: IV Tocilizumab (TCZ) may represent an effective and safe treatment option for patients diagnosed with pars planitis resistant to conventional immunomodulatory therapy and anti-TNF alpha agents.

Purpose: To describe the course of care and outcomes for 3 uveitis patients formerly on Remicade that were non-medically switched to Inflectra., Design: Retrospective observational case series., Methods: • Setting: Tertiary care clinical practice.• Patient population: 3 Uveitis patients, observing both eyes for inflammation as applicable. Patients included if they had been on Inflectra for ≥2 infusions and history of Remicade use. Patients described herein had at least 1 adverse reaction to Inflectra and were switched to Remicade for medical necessity. Patients excluded if they were lost to follow-up or not examined for over 6 months during therapy.• Observation procedures/Interventions: Patients observed for adverse changes in clinical course while on Inflectra. Patients developing these changes on Inflectra were started or restarted on Remicade., Results: The 3 patients described herein developed adverse complications while on Inflectra that required switching to Remicade. They were originally on Remicade, and their clinical course worsened beyond what had been controlled with Remicade alone. Our findings are limited by our small sample size, and further investigation is necessary to explore the scope of effects of non-medical biosimilar switching., Conclusion: Non-medical biosimilar switching from Remicade to Inflectra may induce detrimental side-effects and significant worsening of inflammation in patients with uveitis. Non-medical biosimilar switching from Remicade to Inflectra should be discouraged, and physician input should be sought in establishing an effective and medically-necessary treatment plan for patients with uveitis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To accelerate medical breakthroughs, the All of Us Research Program aims to collect data from over one million participants. This report outlines processes used to construct the All of Us Social Determinants of Health (SDOH) survey and presents the psychometric characteristics of SDOH survey measures in All of Us. A consensus process was used to select SDOH measures, prioritizing concepts validated in diverse populations and other national cohort surveys. Survey item non-response was calculated, and Cronbach's alpha was used to analyze psychometric properties of scales. Multivariable logistic regression models were used to examine associations between demographic categories and item non-response. Twenty-nine percent (N = 117,783) of eligible All of Us participants submitted SDOH survey data for these analyses. Most scales had less than 5% incalculable scores due to item non-response. Patterns of item non-response were seen by racial identity, educational attainment, income level, survey language, and age. Internal consistency reliability was greater than 0.80 for almost all scales and most demographic groups. The SDOH survey demonstrated good to excellent reliability across several measures and within multiple populations underrepresented in biomedical research. Bias due to survey non-response and item non-response will be monitored and addressed as the survey is fielded more completely., (© 2024. The Author(s).)

Objective: The efficiency of B-cell depletion therapy for severe ocular cicatricial pemphigoid (OCP) highlights the key role of B lymphocytes in the immunopathogenesis of OCP. B-cell activating factor (BAFF) is a potent B-cell growth factor and costimulator of immunoglobulin production. Elevated serum BAFF is associated with systemic autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and bullous pemphigoid. We hypothesize that serum BAFF levels are also increased in patients with OCP., Methods: Sera were collected from 30 patients with new-onset active OCP, 9 with disease in remission, 10 with OCP relapse, and 15 healthy control individuals. An enzyme-linked immunosorbent assay was performed to measure the concentration of serum BAFF., Results: BAFF was significantly higher in patients with new-onset active OCP (700.8 ± 181.8 pg/mL) than in healthy control individuals (564.1 ± 133.2 pg/mL; p = 0.014). No significant difference was found between patients with OCP in remission (585.4 ± 216.2 pg/mL) and healthy control individuals. Patients with disease relapse treated with rituximab had an extremely high concentration of BAFF (1721.9 ± 790.8 pg/mL). Longitudinal analysis of serum BAFF from 6 patients showed that BAFF decreased as the disease went from new onset (895.0 ± 240.8 pg/mL) to remission (625.4 ± 199.8 pg/mL; p = 0.003)., Conclusions: BAFF is involved in the active inflammation of OCP. Targeting BAFF with an antagonist may be therapeutically beneficial for patients with refractory OCP, especially those resistant to rituximab., (Copyright © 2022 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression., Competing Interests: Declaration of interests An international patent related to this work has been published under international publication no. WO 2023/047140 A1. R.A.E. has the following conflicts of interest to declare: she has received honoraria from GU-ASCO, Janssen, The University of Chicago, and Dana-Farber Cancer Institute USA as a speaker and educational honorarium from Bayer and Ipsen and is a member of the external expert committee to Astra Zeneca UK. She undertakes private practice as a sole trader at The Royal Marsden NHS Foundation Trust and 90 Sloane Street SW1X 9PQ and 280 Kings Road SW3 4NX, London, UK., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: An ideal Fontan pathway should be capable of adapting to changes in circulatory demands. The external pericardial lateral tunnel Fontan (EPLTF) is constructed of viable, autologous tissue and may be capable of changing in size. We investigated the ability of the EPLTF to enlarge with increasing physiologic demands of somatic growth. Methods: Retrospective review of echocardiographic images for patients with a minimum of five years follow-up after EPLTF. Serial echocardiographic measurements of the EPLTF pathway were obtained at three distinct locations: the inferior vena cava junction with the EPLTF, midsection of the EPLTF, and cross-sectional area of the EPLTF visualized in a four-chamber view. Body surface area (BSA) was calculated at the time of each echocardiographic measurement. Changes in echocardiographic measurements over time were analyzed and compared with changes in BSA. Results: A total of 332 echocardiographic studies from 38 patients were reviewed. Significant enlargement of the EPLTF pathway is observed at the inferior vena caval junction ( P  < .001), midsection ( P  < .01), and cross-sectional area ( P  < .001). Repeated measures correlation between pathway measurements and BSA is highly significant ( P  < .001). Conclusions: The EPLTF pathway enlarges over time in correlation with increasing BSA. Further research is needed to define ideal pathway size, differentiate normal physiologic growth from pathologic enlargement, and correlate changes with clinical outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression., Design: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression., Participants: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer., Methods: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study., Main Outcome Measures: Overall mortality and CM., Results: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration., Conclusions: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

Purpose: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI)., Methods: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications., Results: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient., Conclusions: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated., Competing Interests: D. S. Chu serves as a speaker for Abbvie and Novartis and as a consultant for Aldeyra Therapeutics Dompé, Mallinckrodt and Santen Pharmaceuticals. S. D. Anesi serves as a consultant for Mallinckrodt and Santen Pharmaceuticals, Allakos, Eyepoint, and Takeda and as a speaker for AbbVie, Mallinckrodt, and Eyepoint. A. J. W. Huang serves as a speaker for Mallinckrodt. C. S. Foster serves as a consultant for Aldeyra Therapeutics, Allakos, Bausch & Lomb Surgical, Eyegate Pharma, Genentech, Novartis, and pSivida and as a speaker for Alcon and Allergan and Mallinckrodt pharmaceuticals. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To characterize various ocular inflammatory complications arising from metastatic cutaneous melanoma therapies and their management., Methods: Retrospective case series of patients who were referred to a tertiary uveitis practice for ophthalmic exam All patients received targeted metastatic cutaneous melanoma treatment, including BRAF/MEK inhibitors and various immunotherapies., Results: 109 patients were identified, with 43 (39.4%) having 65 definitive instances of OIAE. Sixteen different OIAE were identified. Ipilimumab monotherapy and ipilimumab/nivolumab combination therapy were most commonly associated. Anterior uveitis was the most common OIAE (18/65, 27.7%). Thirty patients (69.8%) were managed with observation or topical steroid therapy. Only 4 patients required further therapies for OIAE, with one patient not attaining resolution., Conclusions and Relevance: While a broad range of OIAE was identified, most were not vision-threatening and did not require discontinuation of the associated therapy.

Purpose: To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis., Design: Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010)., Methods: Data were harvested by trained expert reviewers, using protocol-driven review of experts' charts. We studied cataract incidence-newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery-in 3923 eyes of 2567 patients with anterior uveitis., Results: Cataract developed in 507 eyes (54/1000 eye-years, 95% CI 49-59). Time-updated risk factors associated with cataract included older age (≥65 vs <18 years: adjusted hazard ratio [aHR] 5.04, 95% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95% CI 1.10-3.14), band keratopathy (aHR 2.23, 95% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95% CI 2.83-4.87), and elevated intraocular pressure ≥30 vs 6-20 mm Hg (aHR 2.57, 95% CI 1.38-4.77). Primary acute (aHR 0.59, 95% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1%-equivalent use (≥2 drops/day) was associated with >2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher., Conclusions: Cataract complicates anterior uveitis in ∼5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To report a case of acute macular neuroretinopathy (AMN) after intravitreal triamcinolone acetonide (TRIESENCE ® ) injection for cystoid macular edema secondary to birdshot chorioretinopathy., Method: A case report., Patient: A 62-year-old female., Results: The patient presented with acutely decreased vision and a ring scotoma around her central vision three days after intravitreal triamcinolone acetonide (TRIESENCE ® ) injection for cystoid macular edema in her right eye (OD) secondary to birdshot chorioretinopathy. She had undergone pars plana vitrectomy, cataract extraction, and secondary intraocular lens implantation OD three months prior to the recent injection. Best-corrected visual acuity (BCVA) was 20/1000 OD and 20/50 OS. Intraocular pressure was 21 mmHg OD and 12 mmHg OS. Fluorescein angiography demonstrated a hypofluorescent area in the perifoveal zone OD. Optical coherence tomography OD depicted hyperreflective areas in the outer nuclear layer, outer plexiform layer, and retinal pigment epithelium. We diagnosed her with AMN OD and started her on brimonidine three times a day OD. She came back a week later with resolved scotoma and her vision improved to 20/60 OD. Five weeks later, BCVA was 20/40 and Intraocular pressures (IOP) was 12 mmHg OD., Conclusions and Importance: Intravitreal triamcinolone injection may be a cause of AMN with cystoid macular edema (CME) and borderline-high intraocular pressure. Brimonidine may be an effective treatment for these patients in the early course of the disease.

Purpose: To compare vision acuity outcomes of long-term steroid therapy compared with immunomodulatory therapy for treatment of sympathetic ophthalmia., Design: Single-center, retrospective, comparative clinical study., Methods: Patients with sympathetic ophthalmia treated from March 2005 to October 2022 with at least 1 year of follow-up were included. Visual acuity outcomes were compared by steroid and immunomodulatory treatment modality., Results: Thirty-five patients with sympathetic ophthalmia were included in the study, with follow-up ranging from 1 to 17 years. Higher rates of vision loss correlated with longer periods of active uveitis and steroid treatment. Lower rates of vision loss correlated with longer periods of uveitis remission on immunomodulatory therapy alone and drug-free remission. Treatment with alkylating agents or combination therapy with an antimetabolite, a biologic-response modifier, and cyclosporine are more likely to result in sympathetic ophthalmia remission., Conclusion: Immunomodulatory therapy leads to superior vision outcomes in cases of steroid-resistant or recurrent sympathetic ophthalmia. Steroid therapy may be useful for acute or recalcitrant sympathetic uveitis but is insufficient for long-term inflammatory control. PRéCIS: This manuscript describes a retrospective analysis of vision outcomes in patients with sympathetic ophthalmia. Results indicate that long-term immunomodulatory therapy is associated with better vision outcomes than long-term steroid therapy for sympathetic ophthalmia treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID)., Methods and Analysis: We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began., Results: The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence., Conclusions: We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence., Trial Registration Number: NCT00116090., Competing Interests: Competing interests: JHK: Betaliq (equity owner); Tarsier Pharma (equity owner). CSF: Aldeyra (consultant, grant support), Allakos (consultant), Bausch & Lomb (consultant, grant support), Eyegate (consultant, grant support, stock), Genentech (consultant), Novartis (consultant, grant support), pSivida (consultant, grant support), Aciont (grant support), Alcon (grant support, lecture fees), Clearside (grant support), Dompé (grant support), Mallinckrodt (grant support, lecture fees), Allergan (lecture fees). JTR: AbbVie (consultant); Gilead (consultant); Janssen (consultant); Eyevensys (consultant); UpToDate (consultant); Pfizer (financial support); Novartis (consultant); Roche (consultant); Alcon Research Institute (financial support); UCB (consultant); Horizon (consultant and finanicial support); Santen (consultant). GAL-C: AbbVie (consultant, lecture fees); Allergan (grant support); Mallinckrodt (consultant, grant support); Sanofi (grant support; lecture fees). EBS: Eyevensys (consultant); Santen (consultant); EyeGate (consultant, financial support); AbbVie (consultant, financial support); Clearside (consultant, financial support); EyePoint (consultant, financial support). JET: AbbVie (consultant); Canfield (consultant); Clearside (consultant); Gilead (consultant); Guidepoint (consultant); Roche (consultant); Tarsier Pharma (Scientific Advisory Board; equity owner); UptoDate (consultant). YIL: Research to Prevent Blindness (grant); Alcon (consultant); Microsurgical Guidance Solutions (equity owner); patents pending: WO2020163845 and USSN: 63/183424. HNS: Janssen (employee). ROK: Santen (employee)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report a case of nonparaneoplastic autoimmune retinopathy with phenotypical features of pericentral retinal degeneration (PRD) who responded to IV immunoglobulin therapy., Methods: A case report. A 27-year-old man presented with recent subacute progressive nyctalopia and photopsia., Results: Dilated fundoscopy demonstrated confluent yellow-white patches along the main temporal vascular arcades with sparing of the central island in the posterior pole. Color vision, fundus autofluorescence, fluorescein angiography, static visual field, and electroretinographic studies were inconclusive for retinal degeneration. Subsequent genetic testing for known mutations was negative. Workup for paraneoplastic autoimmune retinopathy was negative. Antiretinal antibodies were positive. The patient was diagnosed with nonparaneoplastic autoimmune retinopathy and was treated with IV immunoglobulin, which resulted in objective and subjective improvement on electroretinography, visual field, and optical coherence tomography of the retina., Conclusion: Nonparaneoplastic autoimmune retinopathy may present in a patient with the clinical phenotype of PRD. It is essential to rule out nonparaneoplastic autoimmune retinopathy in patients with subacute changes in the natural course of pericentral retinal degeneration because treatment with IV immunoglobulin may be helpful.

Introduction: Juvenile idiopathic arthritis is the most common chronic rheumatologic disease in children. Uveitis is the most common extra-articular manifestation of JIA, and it can be a sight-threatening condition., Areas Covered: In this review article, we discussed epidemiology, risk factors, clinical presentation, supportive laboratory tests, treatment options, and complications of Juvenile idiopathic arthritis and Juvenile idiopathic arthritis associated uveitis. We covered conventional immunomodulatory therapy and biologic response modifiers agents for different types of Juvenile idiopathic arthritis and their associated uveitis. Finally, we discussed the course of disease, functional outcome, and the quality of life of Juvenile idiopathic arthritis and Juvenile idiopathic arthritis-associated uveitis., Expert Opinion: Although clinical outcomes of Juvenile idiopathic arthritis and its associated uveitis have been improved over the past three decades by biologic response modifier agents, a significant proportion of patients require active treatment into adult life therefore screening and monitoring of these patients is required during the patient's entire life. The limited number of food and drug administration approved biologic response modifier agents for the treatment of Juvenile idiopathic arthritis associated uveitis justify more randomized clinical trials with new medications in this field.

Purpose: To search findings that can explain the heterogeneity between Resistant and Responsive patients with birdshot chorioretinopathy., Patients and Methods: This was a retrospective observational case series on "Responsive" versus "Resistant" birdshot chorioretinopathy., Results: One-hundred-eighty and Ninety-nine patients were included in the Responsive and Resistant groups respectively. Multivariate analysis of paraclinical variables at the first visit demonstrated that mean deviation (p = .04), pattern standard deviation (p < .001), optic nerve head leakage (p = .012), large vessel leakage and staining (p = .01), and macular small vessel leakage (p = .03) were statistically significantly different between the two groups; however, at the visit preceding successful therapy, only macular small vessel leakage (p = .01) was statistically significantly different between the two groups., Conclusion: .Small vessel leakage in the macular area and/or optic nerve head leakage at the earliest visit might be risk factors for resistant birdshot chorioretinopathy.

Objective: To compare the demographic, clinical, ancillary testing, and multimodal imaging characteristics of birdshot chorioretinopathy (BSCR) patients with late recurrence and birdshot patients with durable remission., Patients and Methods: This was a retrospective observational case series. The above-mentioned parameters were studied in BSCR patients with late recurrence (group 1) and BSCR patients with durable remission (group 2)., Results: Fifty-five patients were included in this study. The average age of patients was 62.1 ± 11.1 years (range, 35-88 years). Groups 1 and 2 included 20 (36.4%) and 35 (63.6%) patients, respectively. In group 1, the average age of patients was 60.5 ± 10.39 years (range, 35-79 years). The female-to-male ratio was 16:4. In group 2, the average age of patients was 63.1 ± 11.6 years (range, 37-88 years). The female-to-male ratio was 22:13. None of the demographic, clinical, ancillary testing, and multimodal imaging parameters were statistically significantly different between the two groups. Using a receiver operating characteristics (ROC) curve, we found that the ideal duration of successful therapy to induce durable remission was 30 months with 70% sensitivity and 40% specificity (ideal point on the curve). A Kaplan-Meier survival curve demonstrated that late recurrence was seen within 30 months after stopping successful treatment of patients with BSCR., Conclusion: There are no demographic, clinical, ancillary testing, or multimodal imaging characteristics that can predict late recurrence in BSCR patients. However, we found that 30 months of successful treatment may be ideal and recommended., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis., Patients and Methods: Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study., Results: Eighteen patients (33 eyes) were included in the study. Eleven (61.1%) patients [20 (60.6%) eyes] and 7 (38.9%) patients [13 (33.3%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found., Conclusion: RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.

Background: Voltage-gated Na + channels (VGSCs) are functionally upregulated in rat and human prostate cancer (PCa) where channel activity promotes cellular invasiveness in vitro and metastasis in vivo. Ranolazine is a clinically used VGSC inhibitor/anti-anginal drug, which has been shown previously to inhibit breast cancer metastasis in vivo., Methods: Using the Dunning model of rat PCa, the effect of ranolazine applied systemically (by gavage) was tested on the development of primary tumours and metastases following subcutaneous inoculation of Mat-LyLu cells into Copenhagen rats. In addition, human prostate tissue microarrays were used to determine VGSC protein expression in cancerous versus non-cancerous tissue. Several public databases were searched to compare Nav1.7/ SCN9A expression levels in 'normal' vs. PCa tissues., Results: Ranolazine (2.5 and 5 µM) decreased the number of lung metastases by up to 63%. In contrast, primary tumourigenesis was not affected. Ranolazine also reduced the percentage of cells in the metastases expressing Nav1.7, the main VGSC subtype expressed in PCa, but the expression level was higher. In prostate tissue microarrays, VGSC protein expression was significantly higher in cancerous versus non-cancerous tissue. There was no correlation between the VGSC expression and either prostate-specific antigen or Gleason score. In public databases, little information could be found on Nav1.7 protein expression in PCa. In addition, the database information on Nav1.7 mRNA (SCN9A) expression levels did not correlate with previously reported upregulation in PCa cells and tissues., Conclusions: The main conclusions were (i) ranolazine inhibited metastasis and (ii) it was a subpopulation of cells with particularly high levels of Nav1.7 protein that reached the metastatic sites. These data extend earlier studies and suggest that Nav1.7 expression could serve as a functional biomarker of metastatic PCa and that VGSC blockers may be useful as anti-metastatic agents.

In this study, we report a case of multifocal choroiditis that was successfully treated with adalimumab monotherapy. A 25-year-old male presented with a history of bilateral multifocal choroiditis which was resistant to a combination of azathioprine, valacyclovir, and prednisone. Dilated fundoscopy revealed small creamy-yellow lesions around the arcades in both eyes (OU). Indocyanine green angiography (ICGA) revealed active hypocyanescent lesions around the arcades and macula OU. Valacyclovir was stopped, adalimumab subcutaneous injections biweekly were added to the regimen, and prednisone was tapered after the second adalimumab loading dose. At 3-month follow-up, ocular examination and ICGA were unremarkable OU. After 30 months of remission, azathioprine was tapered and stopped. After 40 months of remission, adalimumab was tapered and stopped. Four months after stopping adalimumab injections, the patient returned with new floaters in his right eye (OD). ICGA and macular optical coherence tomography detected active lesions OU. The patient was restarted on adalimumab subcutaneous injections as monotherapy. At 3-month follow-up visit, his symptoms had resolved, and ICGA showed resolution of the lesions OD and improvement of the lesions in the left eye (OS). He has been in remission for 6 months at the time of writing since restarting adalimumab monotherapy. We conclude from this study that long-term adalimumab monotherapy can be employed effectively and safely in the re-treatment of patients with multifocal choroiditis resistant to other immunomodulatory therapy even after successful tapering and discontinuation of concurrent therapies., Competing Interests: No conflicting relationship exists for any author. Dr. C Stephen Foster declares the following: consultancies with Aldeyra Therapeutics (Lexington, MA, USA), Allakos (Redwood City, CA, USA), Bausch & Lomb Surgical, Inc. (Rancho Cucamonga, CA, USA), Eyegate Pharma (Waltham, MA, USA), Genentech (South San Francisco, CA, USA), Novartis (Cambridge, MA, USA), and pSivida (Watertown, MA, USA); grants or grants pending with Aciont (Salt Lake City, UT, USA), Alcon (Aliso Viejo, CA, USA), Aldeyra Therapeutics (Lexington, MA, USA), Bausch & Lomb (Rochester, NY, USA), Clearside Biomedical (Alpharetta, GA, USA), Dompé pharmaceutical (Milan, Italy), Eyegate Pharma (Waltham, MA, USA), Mallinckrodt pharmaceuticals (Staines-upon-Thames, UK), Novartis Pharmaceuticals (Cambridge, MA, USA), pSivida (Watertown, MA, USA), and Santen (Osaka, Japan); payment for lectures including service on speaking bureaus from Alcon (Aliso Viejo, CA, USA), Allergan (Dublin, Ireland), and Mallinckrodt pharmaceuticals (Staines-upon-Thames, UK); and stock or stock options from Eyegate Pharma (Waltham, MA, USA). The other authors have nothing to declare., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To identify prognostic factors for poor visual outcomes in patients with isolated retinal vasculitis and to elucidate the outcome of immunosuppressive treatment without the use of antituberculosis drugs for patients with retinal vasculitis associated with a positive QuantiFERON-TB Gold In-Tube (QFT) test., Methods: A retrospective chart review was performed of patients presenting with retinal vasculitis. After the diagnosis of active retinal vasculitis had been confirmed by fluorescein angiography and other possible causes of retinal vasculitis had been excluded, patients were categorized into two groups by their QFT result. Potential associated factors between the poor and good visual outcome groups were statistically analyzed by the chi-square test and logistic regression model with generalized estimating equations., Results: Seventy-three eyes (48 patients) were enrolled in this study. After univariate analysis, multivariate logistic regression analysis was performed and revealed that logMAR visual acuity at the initial visit ( P = 0.01) and outer retinal disruption ( P = 0.03) were the two factors significantly associated with poor visual outcomes. Systemic corticosteroids were administered without the use of antituberculosis drugs to all 16 cases of presumed tuberculous retinal vasculitis associated with positive QFT (26 eyes), 10 (63%) of whom were given nonsteroidal immunosuppressive drugs and achieved inflammatory control and treatment success., Conclusion: Risk factors leading to poor visual outcome in patients with isolated retinal vasculitis have been identified. Immunosuppressive treatment without antituberculosis drugs seems to be a promising regimen for selected patients with presumed tuberculous retinal vasculitis under vigilant care.

Purpose: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis., Patients and Methods: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL., Results: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage ( p = .005), the presence of vasculitis ( p = .01), the presence of active choroiditis ( p = .01), and the presence of CME on OCT ( p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation ( p < .001) and the last follow-up visit ( p = .014) in the AVLL group., Conclusion: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.