PARACENTRAL ACUTE MIDDLE MACULOPATHY AND OCULAR ISCHEMIC SYNDROME AFTER INTRANASAL STEROID INJECTION: A CASE REPORT AND REVIEW OF THE LITERATURE.

PURPOSE: To describe a case of paracentral acute middle maculopathy and ocular ischemic syndrome after intranasal steroid injection. METHODS: Case report. RESULTS: Following an intranasal steroid injection, the patient experienced an episode of amaurosis fugax in her right eye lasting several minutes. Afterward, her visual acuity returned to baseline, but she noted a persistent central scotoma. Optical coherence tomography demonstrated paracentral acute middle maculopathy and fluorescein angiography showed staining and leakage to peripheral vessels concerning for diffuse ischemia. CONCLUSION: Steroid injections to the face and nasopharynx may result in ischemic and vaso-occlusive events in the retina. Ophthalmologists and other physicians performing these procedures need to be aware of this potential adverse outcome.

ENDOPHTHALMITIS PRESENTING AS RETINAL VASCULITIS LESS THAN 24 HOURS AFTER AFLIBERCEPT INJECTION: A CASE REPORT.

PURPOSE: We describe a case of endophthalmitis caused by Streptococcus salivarius presenting as a retinal vasculitis less than 24 hours after intravitreal injection. METHODS: A case report. RESULTS: The patient progressed from a hemorrhagic retinal vasculitis to severe endophthalmitis with no view to the posterior segment within 24 hours. The visual acuity progressed from 20 of 20 preinjection to light perception within less than 48 after injection. Vitreous tap and injection was performed within 24 hours of intravitreal aflibercept injection, followed by pars plana vitrectomy the next day. The final visual acuity was hand motions. CONCLUSION: Streptococcus salivarius is a virulent organism that may cause an endophthalmitis early after intravitreal injection with an unusual presentation of hemorrhagic retinal vasculitis. A high index of suspicion for infectious endophthalmitis should be maintained for all patients presenting with ocular inflammation and worsening vision in the days after intravitreal injections.

Vitreous and Chorioretinal Lesions in People Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections.

PURPOSE: To determine the prevalence of and to characterize vitreous and chorioretinal lesions, to identify causative organisms, and to correlate symptoms with ophthalmic involvement in people who inject drugs and are hospitalized with bloodstream infection (BSI), related metastatic foci of infection (MFI), or both. DESIGN: An academic hospital-based cross-sectional study. PARTICIPANTS: Patients admitted with BSI or MFI related to injection drug use (IDU). METHODS: Patients underwent a complete eye examination within 72 hours of enrollment. Characteristics including gender; age; race; injection drug of choice (DOC); presence of coinfection with hepatitis B, hepatitis C, or human immunodeficiency virus; pathogen causing systemic infection and type of infection; and history of prior infection related to IDU were recorded. MAIN OUTCOME MEASURES: Presence of vitreous or chorioretinal findings, or both. RESULTS: Ninety-one unique patients with 96 separate hospitalizations for systemic infection were enrolled from March 28, 2018, through March 30, 2020. Vitreous or chorioretinal involvement was identified in 16 of 96 patients (16.7%). The most common ocular findings were intraretinal or white-centered hemorrhage in 9 of 96 patients, chorioretinal infiltrate in 8 of 96 patients, endophthalmitis in 5 of 96 patients, and cotton wool spots in 3 of 96 patients. Of the patients with ocular involvement, only 7 of 16 patients (44%) were symptomatic, and 5 of these were patients with endophthalmitis; the others showed chorioretinal infiltrates or intraretinal or white-centered hemorrhage and cotton wool spots. Staphylococcus aureus was the most common causative pathogen in patients with and without ocular findings. Presence of ocular symptoms, worse visual acuity, and injection DOC of methamphetamine were correlated with the presence of ocular findings. CONCLUSIONS: Patients without ocular symptoms with systemic infections related to IDU may have chorioretinal findings. Further study is needed to characterize better the epidemiologic features of these infections and to identify risk factors for ocular involvement in people who inject drugs.

Swept source OCTA reveals a link between choriocapillaris blood flow and vision loss in a case of tubercular serpiginous-like choroiditis.

Optical coherence tomography angiography (OCTA) is a non-invasive technique that is useful in the diagnosis and management of patients with posterior uveitis. Here we report the use of swept source OCTA (SS-OCTA) in a patient with tuberculosis (TB) associated serpiginous like choroiditis (TB-SLC) that made a full visual recovery following treatment with ATT, local and systemic corticosteroids, and systemic immune modulation. By comparing en face images of choriocapillaris (CC) blood flow before and after treatment, we conclude that the patient's visual recovery was associated with resolution of extensive CC flow deficits. This case highlights the utility of SS-OCTA in the multimodal evaluation of patients with choroidal inflammation, and the potential for good visual recovery in patients treated for TB-SLC.

Quantitative Analysis of the Choriocapillaris in Uveitis Using En Face Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: To perform a quantitative analysis of choriocapillaris (CC) flow deficits (FDs) in patients with uveitis. DESIGN: Retrospective cross-sectional study. METHODS: Swept-source optical coherence tomography based angiography (SS-OCTA) macular volume scans (3 × 3 mm and 6 × 6 mm) were obtained using the Plex Elite 9000. En face CC images were generated and analyzed using an automated FD identification algorithm. Three quantitative metrics were determined for each eye: FD number (FDN), mean FD size (MFDS), and FD density (FDD). Quantitative metrics were compared between uveitis and control eyes. The uveitis cohort was further subdivided by the presence or absence of choroidal involvement, and quantitative metrics were compared between subgroups and normal control subjects. RESULTS: A total of 38 eyes from 38 control subjects and 73 eyes from 73 uveitis subjects were included in this study. Eyes with uveitis have significantly larger CC MFDS (3- × 3-mm scans; P < .0001; 6- × 6-mm scans; P < .0001) and higher FDD (P = .0002; P = .0076, respectively) compared to control eyes. Additional analysis determined that these differences were due to the choroidal disease subgroup, which demonstrates significantly larger MFDS (3 × 3 = 1,108 µm2; 6 × 6 = 1,104 µm2) compared to both normal control eyes (752 µm2; P < .0001; 802 µm2; P < .0001, respectively) and uveitis patients without choroidal involvement (785 µm2; P < .0001; 821 µm2; P < .0001, respectively). No significant differences were found between the quantitative metrics of control subjects and patients without choroidal involvement. CONCLUSIONS: Automated quantification of CC can identify pathological FDs and provide quantitative metrics describing such lesions in patients with uveitis. Posterior uveitis patients have significantly larger CC FDs than patients with other forms of uveitis.

Platelet-Activating Factor (PAF) Receptor Antagonism Modulates Inflammatory Signaling in Experimental Uveitis.

BACKGROUND: The phospholipid mediator platelet-activating factor (PAF) activates an inflammatory response that includes arachidonic acid release and prostaglandin production in the eye, increasing vascular permeability and inflammation. The purpose of this study is to investigate the action of LAU-0901, a novel PAF receptor antagonist, on experimental uveitis. METHODS: Uveitis was induced in Lewis rats by lipopolysaccharide treatment. LAU-0901 was then delivered systemically in different concentrations at plus 4 and 16 hours, or vehicle injected as controls. Additional animals were used for histological analyses of untreated, uveitis, and uveitis-plus-LAU-0901 retinas. Conventional histological and immunohistochemical methods were employed. A slit lamp and Spectral Domain-Ocular Coherence Tomography (SD-OCT) retinal imager was used for anterior segment photography and posterior pole OCT. Rats were euthanized 4 hours after the second LAU-0901 injection in this 24-hour model. Aqueous humor was collected and quantified, and also analyzed for tumor necrosis factor alpha (TNF-α). RESULTS: Uveitic eyes demonstrated hypopyon formation, leukocyte infiltration, and an increase in aqueous protein and TNF-α levels. LAU-0901 treatment resulted in a dose-dependent reduction in inflammation, reflected by reduced total protein levels (up to a 64% reduction). Moreover, hypopyon was prevented, leukocytes were absent in vitreous and aqueous humor, and TNF-α levels were reduced by 91%. CONCLUSIONS: The PAF receptor antagonist LAU-0901 decreases ocular inflammation in a rat model of anterior uveitis in a dose-dependent manner, suggesting that use of this molecule may provide a means to attenuate inflammation onset and offer a future alternative or adjunctive treatment for ocular inflammation.

Cytokines in uveitis.

PURPOSE OF REVIEW: Increasing evidence supports Th17 cells as key mediators of ocular inflammatory disease. Cytokines that are important for the development and pathologic function of these cells are potential therapeutic targets in patients with immune mediated uveitis. This review provides an overview of these cytokines including recent insights about their roles in ocular inflammation from laboratory and clinical studies. RECENT FINDINGS: Interleukin (IL)-6, IL-10, IL-17, IL-22, IL-23 and tumour necrosis factor-alpha (TNFα) are cytokines that have been examined for their functional role in uveitis and their relationship to pathologic Th17 cells. Studies in animal models, particularly in experimental autoimmune uveitis (EAU), have been instrumental in studying the role of these cytokines in disease pathogenesis. More recently, studies on aqueous, vitreous and serum from patients with uveitis using flow cytometry and multiplex ELISA bead-based methodologies have provided insights into the contribution of Th17 cells and the related cytokines in ocular inflammatory diseases. The central role of IL-23 in determining the pathologic Th17 fate has made it an effective therapeutic target in systemic diseases such as psoriasis and thereby an attractive potential target for patients with immune-mediated uveitis. SUMMARY: Th17 cells, and their related cytokines, are important inflammatory mediators in autoimmune uveitis. Animal and human studies continue to provide new information to direct development of new cytokine-targeted therapies for patients with uveitis.

Regulation of intrinsic axon growth ability at retinal ganglion cell growth cones.

PURPOSE: Mammalian central nervous system neurons fail to regenerate after injury or disease, in part due to a progressive loss in intrinsic axon growth ability after birth. Whether lost axon growth ability is due to limited growth resources or to changes in the axonal growth cone is unknown. METHODS: Static and time-lapse images of purified retinal ganglion cells (RGCs) were analyzed for axon growth rate and growth cone morphology and dynamics without treatment and after manipulating Kruppel-like transcription factor (KLF) expression or applying mechanical tension. RESULTS: Retinal ganglion cells undergo a developmental switch in growth cone dynamics that mirrors the decline in postnatal axon growth rates, with increased filopodial adhesion and decreased lamellar protrusion area in postnatal axonal growth cones. Moreover, expressing growth-suppressive KLF4 or growth-enhancing KLF6 transcription factors elicits similar changes in postnatal growth cones that correlate with axon growth rates. Postnatal RGC axon growth rate is not limited by an inability to achieve axon growth rates similar to embryonic RGCs; indeed, postnatal axons support elongation rates up to 100-fold faster than postnatal axonal growth rates. Rather, the intrinsic capacity for rapid axon growth is due to both growth cone pausing and retraction, as well as to a slightly decreased ability to achieve rapid instantaneous rates of forward progression. Finally, we observed that RGC axon and dendrite growth are regulated independently in vitro. CONCLUSIONS: Together, these data support the hypothesis that intrinsic axon growth rate is regulated by an axon-specific growth program that differentially regulates growth cone motility.

Ocular surface neoplasias and human immunodeficiency virus infection.

PURPOSE OF REVIEW: Ocular surface malignancy is a serious complication in HIV infection, but can often result in successful treatment if diagnosed appropriately. In the literature, most reviews focus on information for the ophthalmic community. Here, we provide a review of the literature with the pertinent information for the nonophthalmologist, as they are the first point of contact for most HIV patients. RECENT FINDINGS: Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface malignancy. It can be treated well with surgery or topical chemotherapy, the newest method of treatment. When presenting in young patients, a high percentage have been found to be HIV positive. Kaposi's sarcoma is an AIDS-defining malignancy and critical to diagnose. It cannot be cured, but treatment is effective for keeping it controlled. Conjunctival lymphoma can be recognized with the salmon patch appearance. External beam radiation, systemic chemotherapy, and intralesional injections are the mainstays of treatment. SUMMARY: Ocular surface malignancy manifests significantly in the HIV population. OSSN, Kaposi's sarcoma and conjuctival lymphoma all have different clinical presentations. The capacity of the managing physician to recognize these tumours and refer to an ophthalmologist is essential for appropriate treatment.

Mitochondrial dynamics regulate growth cone motility, guidance, and neurite growth rate in perinatal retinal ganglion cells in vitro.

PURPOSE: Retinal ganglion cell (RGC) death and failed axonal regeneration after trauma or disease, including glaucomatous and mitochondrial optic neuropathies, are linked increasingly to dysfunctional mitochondrial dynamics. However, how mitochondrial dynamics influence axon growth largely is unstudied. We examined intrinsic mitochondrial organization in embryonic and postnatal RGCs and the roles that mitochondrial dynamics have in regulating neurite growth and guidance. METHODS: RGCs were isolated from embryonic day 20 (E20) or postnatal days 5 to 7 (P5-7) Sprague-Dawley rats by anti-Thy1 immunopanning. After JC-1 loading, mitochondria were analyzed in acutely purified RGCs by flow cytometry and in RGC neurites by fluorescence microscopy. Intrinsic axon growth was modulated by overexpressing Krüppel-like family (KLF) transcription factors, or mitochondrial dynamics were altered by inhibiting dynamin related protein-1 (DRP-1) pharmacologically or by overexpressing mitofusin-2 (Mfn-2). Mitochondrial organization, neurite growth, and growth cone motility and guidance were analyzed. RESULTS: Mitochondrial dynamics and function are regulated developmentally in acutely purified RGCs and in nascent RGC neurites. Mitochondrial dynamics are modulated differentially by KLFs that promote or suppress growth. Acutely inhibiting mitochondrial fission reversibly suppressed axon growth and lamellar extension. Inhibiting DRP-1 or overexpressing Mfn-2 altered growth cone responses to chondroitin sulfate proteoglycan, netrin-1, and fibronectin. CONCLUSIONS: These results support the hypothesis that mitochondria locally modulate signaling in the distal neurite and growth cone to affect the direction and the rate of neurite growth.

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth.

Understanding neurite growth regulation remains a seminal problem in neurobiology. During development and regeneration, neurite growth is modulated by neurotrophin-activated signaling endosomes that transmit regulatory signals between soma and growth cones. After injury, delivering neurotrophic therapeutics to injured neurons is limited by our understanding of how signaling endosome localization in the growth cone affects neurite growth. Nanobiotechnology is providing new tools to answer previously inaccessible questions. Here, we show superparamagnetic nanoparticles (MNPs) functionalized with TrkB agonist antibodies are endocytosed into signaling endosomes by primary neurons that activate TrkB-dependent signaling, gene expression and promote neurite growth. These MNP signaling endosomes are trafficked into nascent and existing neurites and transported between somas and growth cones in vitro and in vivo. Manipulating MNP-signaling endosomes by a focal magnetic field alters growth cone motility and halts neurite growth in both peripheral and central nervous system neurons, demonstrating signaling endosome localization in the growth cone regulates motility and neurite growth. These data suggest functionalized MNPs may be used as a platform to study subcellular organelle localization and to deliver nanotherapeutics to treat injury or disease in the central nervous system.

Poor lymphoproliferative responses with low proportion of Gag-specific CD8 TEMRA cells in HIV-1-infected patients showing immunological and virological discordance despite prolonged suppression of plasma viremia.

We investigated in-vitro lymphoproliferative responses and T-cell subsets in 38 HIV-1-infected patients showing impaired restoration of CD4 T cells despite prolonged viral suppression (discordant), and in 42 HIV-1-infected patients showing positive immunological and virological responses to highly active antiretroviral therapy (HAART) (concordant). In comparison to concordant patients, discordant patients showed poor lymphocyte proliferation, lower secretion of IL-2 and IFN-gamma, a lower percentage of perforin and granzyme-B-producing CD8 T cells, and poor differentiation of effector memory CD8 T(EM) cells into CD8 T(EMRA) cells in in-vitro stimulation assays, especially against HIV-1 Gag p24 and one of its peptide pools. Functional CD8 T-cell responses of discordant patients after stimulation with recall antigens, Candida albicans, and tetanus toxoid, were also inferior to concordant patients, but comparable to normal healthy controls. Examination of the multifunctional roles of T cells is imperative in describing the overall magnitude of immune responses to HIV-1. Our results suggest that prolonged suppression of plasma viremia alone does not warrant good qualitative and quantitative CD8 T-cell responses to HIV-1, implying that CD4 T cells are required for maintenance of protective CD8 T-cell responses.