A Remote Consult Retinal Artery Occlusion Diagnostic Protocol.

PURPOSE: To report a novel protocol for diagnosis of retinal artery occlusions at the point of care using OCT and a remote consult model. DESIGN: Retrospective case series and evaluation of a diagnostic test or technology. PARTICIPANTS: Adult patients who presented with painless monocular vision loss and were diagnosed with a nonarteritic retinal artery occlusion. METHODS: OCT machines were placed in the stroke center or emergency department at 3 hospitals within our health system. Patients who presented with painless monocular vision loss were evaluated by the stroke neurology service and an OCT was acquired. The images were interpreted remotely by the retina service. An in-house ophthalmology consult was not required to make the final treatment decision. Eligible patients were treated with intra-arterial tissue plasminogen activator (IA-tPA). Patients were followed by ophthalmology during their admission when an in-house consultation service was available or otherwise evaluated immediately after discharge. MAIN OUTCOME MEASURES: Visual acuity (VA) before and after treatment with IA-tPA; time from last known well (LKW) to treatment; and time from presentation to treatment. RESULTS: In the first 18 months since the protocol went live, 59 patients were evaluated. Twenty-five patients (42%) had a confirmed retinal artery occlusion based on OCT and follow-up examination. Ten patients were eligible for treatment, and 9 patients received treatment with IA-tPA. There was a statistically significant improvement in mean VA from logarithm of the minimum angle of resolution (logMAR) 2.14 to logMAR 0.7 within 24 hours after treatment (P = 0.0001) and logMAR 1.04 after 4 weeks (P = 0.01). Clinically significant improvement was noted in 66% of patients within 24 hours and maintained through 1 month in 56% of all treated patients. The mean time to treatment from LKW was 543 minutes and from presentation at the stroke center was 146 minutes. CONCLUSIONS: We report the successful implementation of a remote consult protocol using point-of-care automated OCT. This novel paradigm demonstrates the potential utility of remote consult services for the diagnosis of time-sensitive ophthalmic emergencies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A Pilot Study of Subclinical Non-Capillary Peripapillary Perfusion Changes in Thyroid-Related Orbitopathy Detected Using Optical Coherence Tomography Angiography.

Purpose: Hemodynamic changes surrounding the optic nerve head are known to occur in thyroid-related orbitopathy (TRO). This pilot study explores the capillary and non-capillary peripapillary perfusion changes of the retina in TRO eyes without dysthyroid optic neuropathy (DON) using optical coherence tomography angiography (OCT-A). Methods: Non-capillary and capillary peripapillary perfusion densities were calculated using single 4.5 × 4.5mm en face "RPC layer" OCT-A scans of 8 TRO patients without DON (8 eyes, mean age 40.6 years, range 23-69 years). Results were compared to a previously published dataset of 133 healthy controls (133 eyes, mean 41.5 years, range 11-83 years). The strength of association was measured between OCT-A perfusion densities and clinical measures of TRO. Results: Non-capillary peripapillary perfusion density in TRO eyes was found to be significantly decreased compared to healthy controls (TRO group 15.4 ± 2.9% vs controls 21.5 ± 3.1%; p < 0.0001). Capillary peripapillary perfusion densities showed no significant difference (TRO group 42.5 ± 1.8% vs controls 42.5 ± 1.5%; p = 1.0). Clinical measures of disease did not correlate well with OCT-A perfusion densities (p>0.05). Conclusion: These findings may represent decreased blood flow and subclinical ischemia to the optic nerve. We discuss possible pathogenic mechanisms of thyroid-related vasculopathy, including vessel wall thickening due to immunologically-induced media enlargement.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AS A PRESENTING SIGN OF CENTRAL RETINAL ARTERY OCCLUSION IN SICKLE CELL DISEASE TREATED WITH TISSUE PLASMINOGEN ACTIVATOR.

PURPOSE: We report the case of a 27-year-old monocular woman with a history of sickle cell disease who received intra-arterial tissue plasminogen activator (tPA) after presenting with acute painless vision loss secondary to incomplete central retinal artery occlusion presenting as paracentral acute middle maculopathy in her left eye. METHODS: Ultrawidefield fundus photography, ultrawidefield fluorescein angiography, en face optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were obtained and reviewed, followed by cerebral angiography and infusion of intra-arterial tissue plasminogen activator. RESULTS: A patient with a history of sickle cell disease presented with a new onset of a dense central scotoma, and the visual acuity diminished to 20 of 200 from baseline 20 of 20 in her left eye. Fluorescein angiogram was nondiagnostic. Optical coherence tomography revealed perifoveal hyper-reflective bands in the inner nuclear layer in a pattern characteristic of paracentral acute middle maculopathy. The patient received intra-arterial tissue plasminogen activator through her left ophthalmic artery shortly after presentation, resulting in a gradual restoration of the visual acuity to 20 of 20 in the three months after the procedure. CONCLUSION: This is the first report describing the use of intra-arterial tissue plasminogen activator to treat incomplete central retinal artery occlusion presenting as a paracentral acute middle maculopathy lesion in a patient with sickle cell disease.

Outcomes of pars plana vitrectomy with subretinal tissue plasminogen activator injection and pneumatic displacement of fovea-involving submacular haemorrhage.

OBJECTIVE: Fovea-involving subretinal haemorrhage is challenging to manage with uncertain visual outcomes. We reviewed outcomes of patients with fovea-involving macular haemorrhage treated with pars plana vitrectomy (PPV) and subretinal tissue plasminogen activator (tPA) with pneumatic displacement. METHODS AND ANALYSIS: This is a retrospective interventional case series. All patients with submacular haemorrhage who underwent PPV with subretinal tPA injection were included. Reasons for exclusion encompassed patients who underwent intravitreal tPA injection in the office without surgery, insufficient follow-up or documentation. Primary outcomes of interest were postoperative visual acuity (VA) at month 1 and 3. Secondary outcomes were median VA at month 3 by location of haemorrhage and underlying diagnosis. RESULTS: Thirty-seven total patients were included. The mean age was 68.2 years, with 54.1% (20/37) females. The most common aetiology was exudative macular degeneration (43.2%), followed by undifferentiated choroidal neovascularisation (CNV) (18.9%), polypoidal choroidal vasculopathy (18.9%), traumatic CNV (10.8%), macroaneurysm (5.4%) and proliferative diabetic retinopathy (2.7%). Median preoperative VA was 20/2000, postoperative month 1 was 20/347 (p<0.01), improving to 20/152 (p<0.01) at month 3. Proportion of patients gaining vision 3+ lines in vision was 15/36 (42%). Mean preoperative central subfield thickness on optical coherence tomography was 512.2 µm for sub-retinal pigment epithelium haemorrhage and 648.2 µm for subretinal haemorrhage (p=0.48). Difference in VA by diagnosis was not significant (p=0.60). CONCLUSIONS: PPV with subretinal tPA injection and pneumatic displacement of submacular haemorrhage offers modest visual recovery for a diverse group of patients. Location of haemorrhage or specific diagnosis may not predict outcome.

ACUTE MACULAR AND PERIPAPILLARY ANGIOGRAPHIC CHANGES WITH INTRAVITREAL INJECTIONS.

PURPOSE: Intravitreal injections acutely and temporarily increase intraocular pressure (IOP), and this may have cumulative long-term effects including an increased risk for glaucoma surgery. This study was designed to measure retinal perfusion density changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased IOP after intravitreal injections. METHODS: Retrospective observational clinical study of 40 eyes (39 patients) with various retinopathies from October 2016 to June 2017 at a tertiary care retina clinic in NYC. Patients were older than 18 years, with vision >20/100, able to fixate and without media opacities precluding OCT angiography, receiving intravitreal bevacizumab or aflibercept for diabetic retinopathy, retinal vein occlusion, macular degeneration, retinal neovascularization, or radiation retinopathy. The 3-mm × 3-mm macular and 4.5-mm × 4.5-mm peripapillary OCT angiography perfusion density, macular OCT thickness, and IOP were measured before and immediately after intravitreal injections. Paired t-test was used to compare preinjection and postinjection values for perfusion density and OCT thickness. Regression analysis was performed for potential effects of baseline IOP, IOP change, and age. RESULTS: Statistically significant decreases in angiographic perfusion density (P < 0.05) were found in most areas of the superficial and deep layer macular OCT angiography, and the overall optic nerve head and the radial peripapillary capillary layer, preferentially temporal. Macular OCT thickness was significantly decreased in the temporal region and increased in the nasal region. Regression analysis showed relationships between age and decreased superficial macular perfusion. Preinjection IOP was only related to OCT thickness in the fovea. Intraocular pressure change was related only to decreased superficial macular perfusion density. CONCLUSION: Intravitreal injections produce acute IOP changes that are associated with reduced macular and peripapillary perfusion density. Therefore, it is possible that patients receiving regular intravitreal injections may be sustaining perfusion-related injury to ocular structures that may produce glaucomatous damage to the macula and optic nerve.

Pain Control after Intravitreal Injection Using Topical Nepafenac 0.3% or Pressure Patching: A Randomized, Placebo-Controlled Trial.

PURPOSE: Pain after an intravitreal injection (IVI) can last up to 7 days and negatively impacts the patient's experience, potentially reducing treatment compliance. We prospectively evaluated topical nepafenac 0.3% suspension and patching for the reduction of pain after IVI. DESIGN: Randomized controlled trial. PARTICIPANTS: Sixty patients receiving an IVI of bevacizumab, aflibercept, or triamcinolone acetonide in 1 eye. METHODS: Participants were randomized equally to receive either a single drop of nepafenac 0.3%, a pressure patch for 2 hours, or a single drop of preservative-free artificial tears (control group). A single-blinded placebo-controlled design was used to mask the topical treatment used. Pain was assessed using the Numeric Pain Rating Scale that ranged from 0 to 10 (horizontal pain scale). Because pain scores were not normally distributed, statistical analysis was performed using a nonparametric randomization-based analysis of covariance. MAIN OUTCOME MEASURE: Pain scores. RESULTS: Fifty-six and 53 patients of the 60 patients enrolled completed the 6- and 24-hour follow-ups, respectively. Numeric Pain Rating Scale scores at 6 and 24 hours after IVI were lower in the nepafenac group (0.8±0.3 and 0.1±0.1, respectively; n = 18) and the patching group (1.3±0.4 and 0.4±0.2, respectively; n = 19) compared with the control group (2.5±0.6 and 0.9±0.4, respectively; n = 19). After controlling for age, gender, number of prior injections, and physician administering the injection, patients in the nepafenac group reported significantly lower pain scores than those in the control group at 6 hours (1.3±0.6 less; P = 0.047) and 24 hours (0.7±0.3 less; P = 0.047). Although the patching group reported lower pain scores than the control group, this was not statistically significant (6 hours, P = 0.24; 24 hours, P = 0.29). CONCLUSIONS: Nepafenac 0.3% was effective as a single drop in reducing pain at 6 and 24 hours after IVI compared with placebo. Limited patching was associated with lower pain scores than placebo, but the difference was not statistically significant. Additional studies are needed to determine the most effective method to maximize the patient's experience after an IVI without sacrificing outcomes.

Palladium-103 plaque radiation therapy for ciliary body melanoma through a functioning glaucoma filtering bleb.

PURPOSE: To provide a clinical description of the long-term outcome of a 103Pd plaque-irradiated ciliary body melanoma with extrascleral extension while attempting to preserve a subadjacent glaucoma filtering bleb. METHODS: A 75-year-old woman with pseudoexfoliative glaucoma for 17 years, 16 years status post argon laser trabeculoplasty, and 15 years status post trabeculectomy in the left eye, was diagnosed with an ipsilateral ciliary body melanoma with visible extrascleral extension. Treatment involved insertion of a 103Pd radioactive plaque over the functioning trabeculectomy, with removal 7 days later. At plaque insertion, amniotic membrane grafts were used to cover the plaque and protect the filtering site. RESULTS: The tumor was successfully treated without clinical evidence of harm to the filtering bleb, with resultant stable intraocular pressure. However, the patient developed blebitis 1.5 years later. Though it resolved with topical antibiotic therapy, the bleb became less succulent. Two years postoperatively, she developed a spontaneous hyphema that resolved after one injection of transscleral bevacizumab 1.25 mg. Her tumor continually regressed in thickness. Without additional glaucoma surgery, her intraocular pressure remained well-controlled on topical medications for 6 years. CONCLUSIONS: Ciliary body melanoma with minimal extrascleral extension beneath a functioning filtering bleb can be treated using radioactive plaque therapy. In this case, we were able to achieve both tumor regression and glaucoma control by covering the plaque with an amniotic membrane graft.

Moraxella atlantae keratitis presenting with an infectious ring ulcer.

PURPOSE: Moraxella atlantae is a rare pathogen. Keratitis from this organism has never been specifically reported or described. In this report we provide the first clinical description and photograph of Moraxella atlantae infectious keratitis. OBSERVATIONS: A 41 year-old man presented with a three day history of left eye pain. He was found to have a corneal ring ulcer and infiltrate from which Moraxella atlantae was cultured. The patient was successfully treated with intensive topical gatifloxacin (0.5%) and fortified tobramycin (1.5%); oral doxycycline was added to reduce corneal thinning. The patient's infection resolved with a residual scar and final best corrected visual acuity of 20/200 OS. CONCLUSIONS AND IMPORTANCE: Moraxella atlantae can present as a ring-shaped infectious corneal infiltrate and ulcer. Ring infiltrates have been observed with other microorganisms, including several other gram negative bacteria and classically, acanthamoeba. Frequently presumed to be purely immunologic, corneal ring infiltrates can have a number of other etiologies, including infectious and toxic. There are different types of immunologic rings as well, making differentiation of corneal rings sometimes difficult for the ophthalmologic generalist and subspecialist alike. In this paper we discuss characteristics of various corneal ring infiltrates, along with their immune pathophysiology. Infectious rings are distinguished from immunologic Wessely rings.

Optic Nerve Sheath Melanoma Presenting as a Central Retinal Vein Occlusion.

A 64-year-old woman, with a history of diabetes and melanoma, developed a central retinal vein occlusion (CRVO) in her left eye. On exam, she had severe disc edema with retinal nerve fiber layer thickening, and anterior deformation of the peripapillary retinal pigment epithelium (RPE)/Bruch membrane layer (ppRPE/BM) toward the vitreous on spectral domain optical coherence tomography (SD-OCT) suggesting an optic nerve sheath (ONS) meningioma. Magnetic resonance imaging findings and ONS biopsy later confirmed a metastatic melanoma. This case demonstrates that the shape of the RPE/BM on SD-OCT may aid in the decision to consider imaging in patients with isolated CRVO.

Early-onset methicillin-resistant Staphylococcus aureus keratitis and late-onset infectious keratitis in astigmatic keratotomy incision following femtosecond laser-assisted cataract surgery.

UNLABELLED: A 79-year-old woman had uneventful femtosecond laser-assisted cataract surgery including paired laser astigmatic keratotomies (AKs) in the right eye. Three weeks postoperatively, a corneal infiltrate developed in the superotemporal AK incision. Cultures grew methicillin-resistant Staphylococcus aureus. The infection was treated with topical fortified vancomycin and tobramycin; full resolution required several months of therapy. Five months after cataract surgery, the patient presented with a second stromal infiltrate, also in the superotemporal AK incision. Despite negative cultures, the infiltrate resolved quickly on a short course of broad-spectrum fortified antibiotics. At 6 months, the corrected distance visual acuity was 20/30. This case demonstrates that infectious keratitis can occur following uneventful femtosecond laser-assisted AK performed concurrently with cataract surgery. We reviewed the literature on infectious keratitis following refractive keratotomy and femtosecond laser-assisted procedures. Several recommendations to prevent these infections are proposed. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

ABCG2-dependent dye exclusion activity and clonal potential in epithelial cells continuously growing for 1 month from limbal explants.

PURPOSE: To determine changes in ABCG2-transport-dependent dye exclusion in outgrowths from limbal explants. METHODS: Human or rabbit limbal strips were deposited onto inserts. Over a month, the segments were twice transferred to new inserts. Fresh tissue (FT) cells, obtained by sequential dispase-trypsin digestion and the cells growing from the explant cultures, were characterized for ABCG2-dependent efflux by flow cytometry using a newly identified substratum, JC1. Rabbit cells were sorted into JC1-excluding (JC1(low)) and main (JC1(main)) cohorts and seeded with feeder 3T3 cells to determine colony formation efficiency (CFE). RESULTS: The JC1(low) cells were all Hoechst 33342-excluding cells and vice versa, establishing the physical equivalence between JC1(low) and the side population (SP). JC1(low) cell content was reduced by three ABCG2-specific inhibitors: FTC, Ko143, and glafenine. JC1(low) percentiles for the fresh human and rabbit cells were 1.4% and 4.1% and CFEs for rabbit JC1(low) and JC1(main) were 1.2% and 5.3%. In contrast, the respective JC1(low) percentiles in the first and second outgrowths were 19.5% and 27.4% and 25.8% and 32.5%, and the rabbit JC1(low) and JC1(main) CFEs were 12.3% and 0.9%. Thus, although in FT the contribution of the JC1(low) cohort to the CFE is minimal, in the explant culture the phenotype incorporates >80% of the CFE. CONCLUSIONS: ABCG2-dependent dye exclusion undergoes a large expansion in explant culture and becomes associated with a high CFE. The transport increase is more pronounced at late outgrowth times, suggesting permanence of stem cells within the explant.

Neuro2A differentiation by Galphai/o pathway.

Signaling from G(i/o)-coupled G protein-coupled receptors (GPCRs), such as the serotonin 1B, cannabinoid 1, and dopamine D2 receptors, inhibits cAMP production by adenylyl cyclases and activates protein kinases, such as Src, mitogen-activated protein kinases 1 and 2, and Akt. Activation of these protein kinases results in stimulation of neurite outgrowth in the central nervous system (CNS) and in neuronal cell lines. This Connections Map traces downstream signaling pathways from G(i/o)-coupled GPCRs to key protein kinases and key transcription factors involved in neuronal differentiation. Components in the Science Signaling Connections Map are linked to Nature Molecule Pages. This interoperability provides ready access to detail that includes information about specific states for the nodes.