Uveitis and Posterior Ophthalmic Manifestations Following the SARS-CoV-2 (COVID-19) Vaccine.

PURPOSE: To present four cases of posterior ophthalmic manifestations associated with a temporal relationship to SARS-CoV-2 vaccination. METHODS: Retrospective case series with a review of clinical findings. RESULTS: Four patients presented with various posterior ophthalmic findings including uveitis, maculopathy, and optic neuropathy. Each of their clinical courses varied in terms of ophthalmic imaging and exam findings. CONCLUSION: The coronavirus disease 2019 (COVID-19) pandemic has ushered in a new wave of challenges to healthcare, epidemiological endeavors, and widespread vaccination efforts. Novel vaccines have been developed for the SARS-CoV-2 virus, including both mRNA and viral vector-based platforms. The ocular manifestations and side effects related to the SARS-CoV-2 vaccine is not well established or understood. There may be an association between vaccination and posterior ophthalmic manifestations.

Multiple Evanescent White Dot Syndrome Presenting in a Patient With Punctate Inner Choroidopathy.

Purpose: This work reports a case of long-standing punctate inner choroidopathy (PIC) presenting with acute-onset multiple evanescent white dot syndrome. Methods: A 44 year-old man presented with new onset of flashes and a peripheral spot of blurry vision in the right eye. His ocular history included PIC in both eyes. Results: Corrected visual acuities and intraocular pressures were normal. Posterior segment examination of the right eye demonstrated old PIC lesions and new, deep-yellow lesions in the posterior pole and midperiphery. Four months later, these lesions had resolved. Conclusions: Coexistence of PIC and multiple evanescent white dot syndrome has been rarely reported, and more research is warranted to investigate a possible shared etiology.

Filtering-Associated Endophthalmitis after Trabeculectomy or Tube-Shunt Implant.

PURPOSE: To determine the rate, clinical features, and outcomes of filtering-associated endophthalmitis in eyes that underwent trabeculectomy or tube-shunt implantation. DESIGN: Retrospective database study with selective chart review. PARTICIPANTS: Eyes that underwent incisional glaucoma surgery at our institution between January 1, 2012, and December 31, 2019. METHODS: An electronic medical record database was used to identify all eyes that underwent trabeculectomy or tube-shunt implantation during the study period. Date of surgery, date of last ophthalmology clinic visit, and filtering-associated endophthalmitis diagnoses were obtained and used to perform a Kaplan-Meier analysis. The log-rank test was used to compare rates of filtering-associated endophthalmitis after trabeculectomy and tube-shunt implantation. Microbiology, management, and clinical outcomes data from patients with filtering-associated endophthalmitis were also collected and analyzed. MAIN OUTCOME MEASURES: Cumulative risk of filtering-associated endophthalmitis as determined by Kaplan-Meier analysis. Visual acuity improvement to within 2 lines of baseline at 3 months of follow-up and globe salvage at last available follow-up in eyes with filtering-associated endophthalmitis. RESULTS: Kaplan-Meier analysis of 1582 eyes that underwent incisional glaucoma surgery yielded a 5-year cumulative incidence for filtering-associated endophthalmitis of 1.32%. No statistically significant differences were found between rate of endophthalmitis after trabeculectomy or tube-shunt implantation (P = 0.761, log-rank test). Seven of 16 cases (43.8%) of filtering-associated endophthalmitis showed positive culture results from either a vitreous sample or explanted tube shunt. Recovery of vision to within 2 lines of pre-endophthalmitis baseline was achieved in 53% of patients at 3 months of follow-up. Rate of globe salvage was 100% at last available follow-up. CONCLUSIONS: Risk of filtering-associated endophthalmitis is persistent and relatively constant for at least 5 years after incisional glaucoma surgery. The overall prognosis of filtering-associated endophthalmitis remains poor; however, good visual and anatomic outcomes can be achieved in some patients with prompt intervention.

Introduction to Machine Learning, Neural Networks, and Deep Learning.

Purpose: To present an overview of current machine learning methods and their use in medical research, focusing on select machine learning techniques, best practices, and deep learning. Methods: A systematic literature search in PubMed was performed for articles pertinent to the topic of artificial intelligence methods used in medicine with an emphasis on ophthalmology. Results: A review of machine learning and deep learning methodology for the audience without an extensive technical computer programming background. Conclusions: Artificial intelligence has a promising future in medicine; however, many challenges remain. Translational Relevance: The aim of this review article is to provide the nontechnical readers a layman's explanation of the machine learning methods being used in medicine today. The goal is to provide the reader a better understanding of the potential and challenges of artificial intelligence within the field of medicine.

Variability in Plus Disease Identified Using a Deep Learning-Based Retinopathy of Prematurity Severity Scale.

PURPOSE: Retinopathy of prematurity is a leading cause of childhood blindness worldwide, but clinical diagnosis is subjective, which leads to treatment differences. Our goal was to determine objective differences in the diagnosis of plus disease between clinicians using an automated retinopathy of prematurity (ROP) vascular severity score. DESIGN: This retrospective cohort study used data from the Imaging and Informatics in ROP Consortium, which comprises 8 tertiary care centers in North America. Fundus photographs of all infants undergoing ROP screening examinations between July 1, 2011, and December 31, 2016, were obtained. PARTICIPANTS: Infants meeting ROP screening criteria who were diagnosed with plus disease and treatment initiated by an examining physician based on ophthalmoscopic examination results. METHODS: An ROP severity score (1-9) was generated for each image using a deep learning (DL) algorithm. MAIN OUTCOME MEASURES: The mean, median, and range of ROP vascular severity scores overall and for each examiner when the diagnosis of plus disease was made. RESULTS: A total of 5255 clinical examinations in 871 babies were analyzed. Of these, 168 eyes were diagnosed with plus disease by 11 different examiners and were included in the study. The mean ± standard deviation vascular severity score for patients diagnosed with plus disease was 7.4 ± 1.9, median was 8.5 (interquartile range, 5.8-8.9), and range was 1.1 to 9.0. Within some examiners, variability in the level of vascular severity diagnosed as plus disease was present, and 1 examiner routinely diagnosed plus disease in patients with less severe disease than the other examiners (P < 0.01). CONCLUSIONS: We observed variability both between and within examiners in the diagnosis of plus disease using DL. Prospective evaluation of clinical trial data using an objective measurement of vascular severity may help to define better the minimum necessary level of vascular severity for the diagnosis of plus disease or how other clinical features such as zone, stage, and extent of peripheral disease ought to be incorporated in treatment decisions.

Gordonia bronchialis-Associated Endophthalmitis, Oregon, USA.

Gordonia bronchialis is an aerobic actinomycetes that rarely causes infections in humans. Few reports describe Gordonia spp. causing eye-related infections. We report a case of chronic infectious endophthalmitis in Oregon, USA, associated with infection by G. bronchialis.

MULTIMODALITY OCULAR IMAGING IN A CASE REPORT OF HYPERVISCOSITY SYNDROME ASSOCIATED WITH LYMPHOPLASMACYTIC LEUKEMIA: THE IMAGES TELL THE STORY.

PURPOSE: To report the clinical course of a patient with ocular manifestations of hyperviscosity syndrome associated with Waldenström macroglobulinemia, and for the first time, video imaging of mobile emboli in the conjunctival and retinal vasculature. METHODS AND PATIENT: A 60-year-old woman with newly diagnosed Waldenström macroglobulinemia, with no visual complaints was evaluated by the Ophthalmology service for a baseline ocular examination. RESULTS: At presentation, ocular examination revealed a visual acuity of 20/25 in each eye. Slit lamp examination showed mobile white emboli throughout the conjunctival vasculature of both eyes, which was captured on video. Dilated fundus examination revealed peripheral vascular occlusion along with extensive collateral formation in both eyes and as dilation of vessels at the posterior pole of the left eye. Mobile arterial and venous emboli were also observed in the retinal vasculature, which were captured with slit-lamp color and infrared reflectance video imaging. CONCLUSION: Hyperviscosity syndrome is a rare circulation sequelae that occurs when blood is thickened secondary to an increase in immunoglobulins or a hyperproliferation of blood components as in bone marrow dyscrasias. The increase in viscosity is plainly observable in the retinal circulation, and this syndrome is often diagnosed based on visual symptoms and fundus examination. We report a patient with Waldenström macroglobulinemia who presented with multiple ocular manifestations of hyperviscosity syndrome despite the absence of visual complaints. Ophthalmologists should be aware that regardless of the lack of any subjective visual changes, ocular findings of hyperviscosity syndrome should prompt quick referral to a Hematology Oncologist for evaluation of other end-organ damage. We also for the first time, provide video documentation of mobile emboli in the conjunctival and retinal vasculature.

INTERMEDIATE UVEITIS ASSOCIATED WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, AND CERVICAL ADENITIS SYNDROME.

BACKGROUND/PURPOSE: To report two novel cases of intermediate uveitis associated with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome. METHODS: Observational case reports and review of the literature. RESULTS: Both patients in this report had an established diagnosis of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome before the onset of ocular inflammation. Infectious and noninfectious systemic conditions known to be associated with intermediate uveitis were excluded. Intermediate uveitis was confirmed clinically in both patients by the presence of vitritis, snowballs, and peripheral snowbanks in the region of the pars plana. Both cases had a course characterized by recurrent inflammation; in which systemic steroid treatment, and in one case, immunomodulatory therapy was necessary. CONCLUSION: Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome is an auto-inflammatory fever disorder in childhood. Although other auto-inflammatory disorders such as, Blau syndrome, Muckle-Wells syndrome, and Behcets disease have been associated with various forms of uveitis, Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis has never been reported to be associated with any type of ocular inflammation. We describe for the first time, two cases of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome presenting with intermediate uveitis.

Reclassifying Idiopathic Uveitis: Lessons From a Tertiary Uveitis Center.

PURPOSE: Idiopathic uveitis is frequently the most common diagnosis in series from uveitis clinics. This study sought to determine the percentage of patients initially diagnosed as idiopathic, noninfectious uveitis referred to a tertiary uveitis center who were subsequently found to have an identifiable cause of uveitis. DESIGN: Retrospective case series. METHODS: We performed a computerized database analysis of 179 consecutive patients who were referred to our practice with the diagnosis of idiopathic, noninfectious uveitis between 2008 and 2016. Patients were evaluated by a thorough history and ophthalmic examination with selected laboratory testing targeted by clues from the history and examination. Standardization of Uveitis Nomenclature (SUN) criteria were used to better assess different types of uveitis. RESULTS: Fifty-two out of 179 (29.0%) patients initially diagnosed with idiopathic uveitis were subsequently diagnosed with an underlying condition. Among patients referred with a diagnosis of idiopathic disease, female patients were most commonly affected (121/179; 67.6%). Among subsequent diagnoses, sarcoidosis was the most common (19/52 or 36.5%), followed by HLA-B27-associated uveitis (11/52, 21.1%), infectious uveitis (6/52, 11.5%), tubulointerstitial nephritis with uveitis (6/52, 11.5%), and juvenile idiopathic uveitis (4/52, 7.7%). Other diagnosable conditions included Behçet disease, multifocal choroiditis, panuveitis, Crohn disease, multiple sclerosis, and relapsing polychondritis. An underlying condition was not found in 127 of 179 (70.9%) patients. CONCLUSIONS: We report that 29% of patients referred to our tertiary uveitis center diagnosed as "idiopathic" had an associated identifiable cause. Identifying an underlying condition associated with uveitis could be potentially lifesaving for some illnesses (eg, sarcoidosis with cardiac involvement) and is critical to management (eg, infection). Although we were able to use limited testing to classify many patients who had been previously incorrectly labeled with idiopathic uveitis, idiopathic uveitis remains the most common diagnosis in our uveitis clinic.

Molecular diagnosis and ocular imaging of varicella zoster virus associated neuroretinitis.

PURPOSE: To report a case of varicella zoster virus associated neuroretinitis confirmed via polymerase chain reaction analysis of ocular fluid. OBSERVATIONS: A 30-year-old man presented with a 1-week history of decreased vision in his left eye and ulcerative skin lesions above his left eyebrow. On exam, he had clinical findings consistent with neuroretinitis characterized by optic disc edema and formation of a macular star. Polymerase chain reaction analysis of aqueous fluid was positive for varicella zoster virus. He was treated with oral valacyclovir with excellent resolution of his symptoms and clinical findings. CONCLUSIONS AND IMPORTANCE: Varicella zoster virus is a rare cause of neuroretinitis. We report for the first time a case of varicella zoster virus associated neuroretinitis confirmed by polymerase chain reaction analysis of ocular fluid. Molecular testing of ocular tissue may lead to a definitive diagnosis.

Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?

PURPOSE OF REVIEW: The intestinal microbiome is thought to play a role in the pathogenesis of inflammatory bowel disease (IBD). There are many shared clinical manifestations between IBD and spondyloarthritis (SpA), of which the most common are peripheral arthritis and uveitis. Clinical overlap along with similar genetics between these diseases suggests a possible shared pathogenetic mechanism, which might center on the intestinal microbiota. In this review, we discuss the available evidence that SpA is a microbiome-driven disease and indicate how SpA-associated uveitis could be tied to gut dysbiosis. We conclude by discussing different treatment paradigms targeting the intestinal microbiome for SpA. RECENT FINDINGS: Recent studies support the growing evidence of the intestinal microbiome as a crucial player in SpA disease pathogenesis. There is emerging evidence that the gut microbiome may play a causative role in uveitis. SUMMARY: The field is beginning to discover a new level of understanding how the intestinal microbiome is involved in SpA. Treatment methods to alter intestinal microbiota to treat SpA-related diseases are still in its infancy.

Long-term follow-up of autosomal dominant Stargardt macular dystrophy (STGD3) subjects enrolled in a fish oil supplement interventional trial.

BACKGROUND: Earlier studies have raised the notion that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplementation could be a useful intervention in autosomal dominant Stargardt macular dystrophy (STGD3). We sought to assess whether fish oil supplementation has a beneficial effect on the clinical course of STGD3 secondary to a mutation in the ELOVL4 gene. MATERIALS AND METHODS: Eleven patients with STGD3 were enrolled in an 8-year open-label, clinical interventional study of over-the-counter fish oil supplements at a recommended daily dose of 650 mg EPA and 350 mg DHA (NCT00420602). Subjects had annual eye examinations with complete imaging, visual function testing, and blood lipid analyses. Compliance with therapy was measured by periodic patient self-report and with serum and red blood cell biomarkers of lipid consumption. Paired sample t-tests were used to measure differences in mean values of visual acuity, lipid biomarkers, and contrast sensitivity obtained at baseline and the last follow-up. RESULTS: All subjects showed progression of their maculopathy, and we could not discern a beneficial effect of the intervention. Compliance with the recommended fish oil supplement intervention was poor as assessed by patient self-report and biomarkers of lipid consumption. CONCLUSIONS: Our inability to detect a benefit of fish oil could be the result of small subject numbers, poor compliance, or intervention too late in the course of the disease. We still advise STGD3 patients to consume fish or fish oil regularly, and we recommend that pre-symptomatic children with ELOVL4 mutations should be especially targeted for these interventions.

Retinal Manifestations of Juvenile Dermatomyositis: Case Report of Bilateral Diffuse Chorioretinopathy with Paracentral Acute Middle Maculopathy and Review of the Literature.

PURPOSE: To review a case of bilateral diffuse chorioretinopathy as a presenting sign of juvenile dermatomyositis (JDM) and review the literature regarding retinal manifestations associated with this disease. METHODS: Review of case record and literature regarding retinal manifestations related to juvenile dermatomyositis. RESULTS: A 13-year-old girl presented with bilateral diffuse chorioretinopathy as the presenting sign of juvenile dermatomyositis. A review of the literature suggests that retinopathy associated with JDM is a rare finding that is symptomatic to patients and often responds to systemic treatment of juvenile dermatomyositis. This is also the first documented case of paracentral acute middle maculopathy in the setting of juvenile dermatomyositis. CONCLUSION: Chorioretinopathy is a rare finding in juvenile dermatomyositis. While all patients with JDM likely do not warrant screening ophthalmologic examinations, any patient who has visual symptoms should have a careful dilated examination to evaluate for retinopathy or steroid-induced cataracts.

MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To analyze macular pigment (MP) amount and distribution in patients with macular telangiectasia Type 2 receiving oral zeaxanthin supplementation in a randomized, open-label, interventional trial. METHODS: Eight macular telangiectasia Type 2 patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, best-corrected visual acuity, contrast sensitivity, fundus biomicroscopy, color fundus photography, autofluorescence imaging, optical coherence tomography, and serum carotenoid levels were tested. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. Concentration of MP was analyzed and calculated from autofluorescence imaging obtained at 488-nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography. RESULTS: The majority of patients had definite increases in the intensity of hypofluorescent ring of MP, but none of them deposited MP centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal optical coherence tomographic features. Yellowish, hypofluorescent crystals appeared in one patient's macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20-mg zeaxanthin supplement. CONCLUSION: Based on the current study, zeaxanthin supplementation does not result in any visual benefit in patients with macular telangiectasia Type 2 and does not reestablish a normal peaked distribution of MP in the fovea. One patient developed a novel, reversible, crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.

Vellus Hair Cyst of the Orbit.

Eruptive vellus hair cysts are a developmental abnormality of vellus hair follicles that result in small cystic papules occurring most frequently on the chest and proximal extremities. Lesions of the ocular adnexa are extremely rare, and to the best of the authors knowledge, involvement of the orbit has never been reported. The authors describe a patient with an eruptive vellus hair cyst involving the orbit.

Cone degeneration following rod ablation in a reversible model of retinal degeneration.

PURPOSE: Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those observed in nonregenerative models. They also asked whether rod loss was reversible. METHODS: The authors generated transgenic X. laevis expressing the Escherichia coli enzyme nitroreductase (NTR) under the control of the rod-specific rhodopsin (XOP) promoter. NTR converts the antibiotic metronidazole (Mtz) into an interstrand DNA cross-linker. A visually mediated behavioral assay and immunohistochemistry were used to determine the effects of Mtz on the vision and retinas of XOPNTR F1 tadpoles. RESULTS: NTR expression was detected only in the rods of XOPNTR tadpoles. Mtz treatment resulted in rapid vision loss and near complete ablation of rod photoreceptors by day 12. Müller glial cell hypertrophy and progressive cone degeneration followed rod cell ablation. When animals were allowed to recover, new rods were born and formed outer segments. CONCLUSIONS: The initial secondary cellular changes detected in the rodless tadpole retina mimic those observed in other models of retinal degeneration. The rapid and synchronous rod loss in XOPNTR animals suggested this model may prove useful in the study of retinal degeneration. Moreover, the regenerative capacity of the Xenopus retina makes these animals a valuable tool for identifying the cellular and molecular mechanisms at work in lower vertebrates with the remarkable capacity of retinal regeneration.

Role of osteoblast-fibroblast interactions in the formation of the ligament-to-bone interface.

The anterior cruciate ligament (ACL) inserts into bone through a characteristic fibrocartilagenous interface, which is essential for load transfer between soft and hard tissues. This multi-tissue interface is lost post ACL reconstruction, and the lack of an anatomic fibrocartilage interface between graft and bone remains the leading cause of graft failure. Currently, the mechanism of interface formation is not known. As a fibrocartilage-like tissue is found within the bone tunnel post ACL reconstruction, we hypothesize that fibroblast-osteoblast interactions at the graft-to-bone junction play a role in fibrocartilage formation. To test this hypothesis, a co-culture model permitting osteoblast-fibroblast communications was used to determine the effects of heterotypic interactions on cell phenotype and the development of fibrocartilage-relevant markers in vitro. It was found that co-culture decreased cell proliferation and osteoblast-mediated mineralization, while inducing fibroblast-mediated mineralization. Moreover, the expression of interface-relevant markers such as collagen type II and aggrecan were detected. Our findings suggest that osteoblast-fibroblast interactions may lead to cell trans-differentiation and eventual fibrocartilage formation. These results provide new insight into the mechanism of fibrocartilage formation, which are critical for interface tissue engineering and achieving biological fixation of soft tissue grafts to bone.