Initial Occurrence of Bilateral Anterior Uveitis in a Patient with Juvenile Idiopathic Arthritis following Discontinuation of Topical Steroids after Bilateral Strabismus Surgery.

Post-operative inflammation is a well-known complication of intraocular surgery. This is especially true in patients with a prior history of uveitis or with a predisposition for an inflammatory response. We report the first published case of a patient who developed bilateral anterior uveitis after bilateral strabismus surgery. It was the first episode of uveitis for this patient who had a pre-existing diagnosis of juvenile idiopathic arthritis.

Novel Case of Multifocal Choroiditis following Powassan Virus Infection.

PURPOSE: To present a case study that describes novel ocular manifestations of Powassan virus encephalitis using fundus imaging. STUDY DESIGN: Case Report. RESULTS: In this case study, fundus photographs, fundus autofluorescence, and fluorescein angiography were used to highlight Powassan virus-induced multifocal choroiditis with linear streaks. CONCLUSIONS: Our case study demonstrates novel retinal findings of Powassan virus, a pattern which is commonly described in eyes infected with West Nile Virus, another type of flavivirus.

TREATMENT OF REFRACTORY TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS WITH INTRAVITREAL METHOTREXATE.

PURPOSE: To describe a case of tubercular serpiginous-like choroiditis that progressed, despite antitubercular medication, corticosteroids, and immunomodulatory treatment, which ultimately quieted after two intravitreal methotrexate injections. METHODS: Case report. RESULTS: A 35-year-old woman reported a shadow in the left eye for 2 weeks. She presented with tubercular serpiginous-like choroiditis in the right eye 2 years prior. At that time, she was started on antituberculosis therapy but was noncompliant and lost to follow-up. On re-presentation, there was a new active left-eye serpiginous lesion, with repeat positive QuantiFERON gold testing. Four antituberculosis drugs were started, followed by corticosteroids and azathioprine, with continued progression despite aggressive treatment. She was finally given 2 intravitreal methotrexate injections (400 µg/0.1 cc) 1 month apart, with final arrest of lesion extension. The uveitis remained quiet for over 24 months, and the patient was able to discontinue all systemic therapy. CONCLUSION: Intravitreal methotrexate injections halted progression of treatment-refractory tubercular serpiginous-like choroiditis.

TUBERCULOUS CHOROIDITIS IN PATIENT WITH VOGT-KOYANAGI-HARADA DISEASE.

PURPOSE: To describe a novel case of intraocular tuberculosis (TB) arising in a patient undergoing treatment for Vogt-Koyanagi-Harada disease, and to highlight the use of spectral domain optical coherence tomography for helping confirm the diagnosis and monitor treatment response. METHODS: Case report of a patient with Vogt-Koyanagi-Harada disease on prednisone, with acute clinical changes suspicious for bilateral tuberculous choroiditis. Spectral optical coherence tomography, fundus photography, and B-scan ultrasonography were all used to capture the acute lesions, and to monitor their responses after initiation of anti-TB therapy. RESULTS: New subretinal lesions arose bilaterally, as characterized by spectral domain optical coherence tomography, and appeared to regress after a first round of anti-TB therapy, thereby helping confirm the presumed diagnosis of intraocular TB. A new peripheral choroidal lesion arose shortly after temporary cessation of antimicrobial treatment, and again regressed once four-drug therapy was instituted, with no recurrent lesions thereafter. CONCLUSION: The use of multimodal imaging was instrumental in the management of a rare case of intraocular TB arising in the setting of underlying Vogt-Koyanagi-Harada disease.

MULTIMODAL IMAGING OF IGG4-RELATED PAPILLITIS AND RETINAL DISEASE.

PURPOSE: To report a case of IgG4-related ophthalmic disease, which presented with papillitis and subretinal deposits. METHODS: Observational case report with multimodal imaging. RESULTS: A 52-year-old man with a history of persistent lymphadenopathy presented with decreased vision in his left eye. Funduscopic examination demonstrated cuticular drusen in both eyes and florid edema of the left optic nerve, along with scattered circumscribed grey-yellow subretinal deposits that were distinct from the cuticular drusen. Swept-source optical coherence tomography demonstrated a hyper-reflective subretinal material corresponding to the grey-yellow subretinal deposits on clinical examination along with diffuse outer retinal disruption. Fundus autofluorescence revealed scattered hypoautofluorescence corresponding to cuticular drusen and also larger patches of hypoautofluorescence corresponding to the grey-yellow subretinal deposits. Fluorescein angiography demonstrated hypofluorescence corresponding to the large subretinal deposits and leakage at the optic nerve. Lymph node biopsy demonstrated IgG4-positive plasma cells and elevated serum IgG4 levels leading to a diagnosis of IgG4-related ophthalmic disease. The patient was treated with oral prednisone with subsequent resolution of the optic nerve edema. CONCLUSION: We describe multimodal imaging of unique retinal and optic nerve findings associated with IgG4-related ophthalmic disease. Our report broadens the spectrum of ocular involvement associated with IgG4-related disease.

Nab-paclitaxel-induced cystoid macular edema in a patient with pre-existing optic neuropathy.

Paclitaxel is a widely used chemotherapy agent that has rarely been associated with ophthalmic toxicities. Cystoid macular edema is one such rare side effect of paclitaxel therapy. Its pathophysiology remains poorly understood. Here, we report on a 69-year-old woman who developed cystoid macular edema associated with the albumin-bound formulation of paclitaxel after several months of therapy for breast cancer. After 2 months of drug withdrawal, her vision improved and there was a significant improvement in the macular edema by imaging with spectral-domain optical coherence tomography. Oncologists using taxane agents should be aware of this rare adverse outcome for timely patient referral to an ophthalmologist and appropriate treatment to preserve a patient's visual acuity.

EXPANDED CLINICAL SPECTRUM OF MULTIPLE EVANESCENT WHITE DOT SYNDROME WITH MULTIMODAL IMAGING.

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

Optical Coherence Tomography Imaging of Presumed Sarcoid Retinal and Optic Nerve Nodules.

PURPOSE: To characterize nodular lesions of the retina and optic nerve with spectral-domain optical coherence tomography (SD-OCT) in patients with sarcoidosis. METHODS: This is a retrospective series of 6 eyes from 5 patients with an established diagnosis of sarcoidosis, with clinically detected nodules of the optic nerve or retina. All lesions were imaged with fundus photography and SD-OCT on presentation, and followed with serial imaging after treatment with corticosteroids and/or immunomodulatory therapy. RESULTS: Spectral OCT through the lesions revealed nodular hyperreflective processes obscuring the retinal layers or optic cup, with local structural changes, including subretinal and intraretinal fluid. After treatment with corticosteroids and/or immunosuppression in 4 followed patients, all lesions regressed with improvement in associated structural changes, but did not entirely disappear. CONCLUSIONS: Spectral OCT can be useful in identifying lesion morphology and location, and in tracking the response to treatment in eyes with posterior-segment nodules, presumably secondary to sarcoidosis.

Adaptive optics imaging of cone mosaic abnormalities in acute macular neuroretinopathy.

BACKGROUND AND OBJECTIVE: To assess the cone photoreceptor mosaic in acute macular neuroretinopathy (AMN) using adaptive optics (AO) imaging. PATIENTS AND METHODS: Four patients with AMN were evaluated retrospectively by near-infrared reflectance (IR) confocal scanning laser ophthalmoscopy (SLO), spectral-domain optical coherence tomography (SD-OCT), and a flood-illuminated retinal AO camera. Microperimetry was performed in one patient. RESULTS: The cone photoreceptor density was decreased at the level of the AMN lesions. The cone mosaic disruption appeared heterogeneous and more widespread than the lesion detected in the IR-SLO and SD-OCT images. The areas of cone loss correlated with SD-OCT and microperimetry. After resolution of the AMN lesion on IR-SLO, there was incomplete recovery of the cone photoreceptor mosaic. CONCLUSION: Cone photoreceptor damage and reconstitution were documented in vivo at the cellular level in AMN using AO imaging. AO imaging appeared more sensitive than combined IR-SLO and SD-OCT to detect and follow photoreceptor damage in patients with AMN.

Success with single-agent immunosuppression for multifocal choroidopathies.

PURPOSE: To evaluate the success of single-agent immunosuppression for patients with the posterior uveitides, birdshot chorioretinitis, multifocal choroiditis with panuveitis, and punctate inner choroiditis. DESIGN: Retrospective case series. METHODS: setting: Tertiary care uveitis practices. population: Patients initiated on immunomodulatory therapy. intervention: Patients were treated with prednisone 1 mg/kg and mycophenolate 2 g daily. Prednisone was tapered after 1 month. Immunosuppression was escalated to mycophenolate 3 g daily, with addition of a second agent, as needed, to achieve treatment success. outcome measure: Treatment success, defined as no disease activity with prednisone dose ≤10 mg daily, at 6, 12, and 24 months. RESULTS: Twenty-seven patients were followed. Mean presentation and 2-year follow-up acuities were 20/41 and 20/42, respectively. For birdshot chorioretinitis, mean (±standard deviation) quantitative Goldmann visual field scores improved from 761 ± 69 degrees (IV/4 isopter) and 496 ± 115 degrees (I/4 isopter) at presentation to 784 ± 57 degrees and 564 ± 125 degrees, respectively. Prednisone was successfully tapered in 95% of patients; mean prednisone doses at 1 and 2 years were 5.3 ± 4.1 and 5.7 ± 4.8 mg/day, respectively. At 2 years, prednisone was discontinued in 11% of patients. Treatment success was achieved in 74% of patients on 1 immunosuppressant, and in an additional 21% of patients on 2 agents, for an overall 95% success rate at 2 years. CONCLUSIONS: Posterior uveitides can be treated with 1 agent in most patients, but the data suggest a need to escalate therapy to higher mycophenolate doses, and in one fifth of cases to add a second agent to maintain disease suppression with acceptably low prednisone doses.

Paracentral acute middle maculopathy: a new variant of acute macular neuroretinopathy associated with retinal capillary ischemia.

IMPORTANCE: With the advent of more sophisticated imaging systems, such as spectral domain optical coherence tomography (SD-OCT), disruption of the inner segment/outer segment (IS/OS) band, and thinning of the outer nuclear layer (ONL) have been identified in association with acute macular neuroretinopathy (AMN). OBJECTIVES: To characterize a new SD-OCT presentation of AMN as a paracentral acute middle maculopathy and to describe multimodal imaging findings that implicate an underlying pathogenesis related to retinal capillary ischemia. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational case series (January 1, 2012, to January 1, 2013) reviewing clinical and imaging data from 9 patients (11 eyes) with AMN at 6 tertiary referral centers. Lesions were classified as type 1 or 2 in relation to the SD-OCT location of the lesion above (type 1) or below (type 2) the outer plexiform layer (OPL) at 6 tertiary referral centers. RESULTS: Of the 9 patients, 5 were female and 4 were male (mean age, 47.6 years; range, 21-65 years). All patients presented with an acute paracentral scotoma and demonstrated a classic dark gray paracentral lesion with near-infrared imaging. Visual acuity ranged from 20/15 to 20/30. Six eyes (5 patients) had type 1 SD-OCT lesions, also referred to as paracentral acute middle maculopathy, and 5 eyes (4 patients) had type 2 SD-OCT lesions. Although type 1 lesions lead to inner nuclear layer (INL) thinning, type 2 lesions resulted in ONL thinning. Type 2 lesions were always associated with significant outer macular defects, including disruption of the inner segment/outer segment and outer segment/retinal pigment epithelium bands, whereas type 1 lesions spared the outer macula. CONCLUSIONS AND RELEVANCE: Paracentral acute middle maculopathy may represent a novel variant of AMN that affects the middle layers of the macula above the OPL as diagnosed with SD-OCT imaging. Two types of AMN lesions may be seen with SD-OCT occurring above and below the OPL. Type 1 refers to hyperreflective bands in the OPL/INL region with subsequent INL thinning. Type 2 is hyperreflective bands in the OPL/ONL region with subsequent ONL thinning. Type 2 lesions may be associated with concomitant defects of the inner segment/outer segment layer. We propose that each of these lesions may be explained by occlusion of either the superficial capillary plexus (type 1) or deep capillary plexus (type 2) located in the innermost and outermost portion of the INL, respectively, immediately adjacent to each corresponding lesion type.

Outer retinal tubulation in degenerative retinal disorders.

PURPOSE: To demonstrate outer retinal tubulation (ORT) in various degenerative retinal disorders. METHODS: This was a retrospective review of the multimodal imaging of 29 eyes of 15 patients with various retinal dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features of ORT and its evolution over time were analyzed using spectral-domain optical coherence tomography data. RESULTS: Outer retinal tubulation was identified as round or ovoid structures with hyperreflective borders in pattern dystrophy (six eyes), acute zonal occult outer retinopathy (five eyes), retinitis pigmentosa (four eyes), Stargardt disease (four eyes), gyrate atrophy (two eyes), choroideremia (two eyes), and various other degenerative conditions. These structures appeared to develop from the invagination of photoreceptors at the junction of intact and atrophic outer retina. During follow-up, the number and distribution of ORT largely remained stable. As zones of atrophy enlarged, the frequency of ORT appeared to increase. The ORT structures were found in <10% of patients with retinitis pigmentosa, Stargardt disease, or pattern dystrophy. CONCLUSION: Outer retinal tubulation is found in various degenerative retinal disorders that share in common damage to the outer retina and/or retinal pigment epithelium. The presence of ORT may be an indicator of underlying disease stage and severity.

State-dependent conformations of the translocation pathway in the tyrosine transporter Tyt1, a novel neurotransmitter:sodium symporter from Fusobacterium nucleatum.

The gene of a novel prokaryotic member (Tyt1) of the neurotransmitter:sodium symporter (NSS) family has been cloned from Fusobacterium nucleatum. In contrast to eukaryotic and some prokaryotic NSSs, which contain 12 transmembrane domains (TMs), Tyt1 contains only 11 TMs, a characteristic shared by approximately 70% of prokaryotic NSS homologues. Nonetheless upon heterologous expression in an engineered Escherichia coli host, Tyt1 catalyzes robust Na+-dependent, highly selective l-tyrosine transport. Genetic engineering of Tyt1 variants devoid of cysteines or with individually retained endogenous cysteines at positions 18 or 238, at the cytoplasmic ends of TM1 and TM6, respectively, preserved normal transport activity. Whereas cysteine-less Tyt1 was resistant to the inhibitory effect of sulfhydryl-alkylating reagents, N-ethylmaleimide inhibited transport by Tyt1 variants containing either one or both of the endogenous cysteines, and this inhibition was altered by the substrates sodium and tyrosine, consistent with substrate-induced dynamics in the transport pathway. Our findings support a binding model of Tyt1 function in which an ordered sequence of substrate-induced structural changes reflects distinct conformational states of the transporter. This work identifies Tyt1 as the first functional bacterial NSS member putatively consisting of only 11 TMs and shows that Tyt1 is a suitable model for the study of NSS dynamics with relevance to structure/function relationships of human NSSs, including the dopamine, norepinephrine, serotonin, and gamma-aminobutyric acid transporters.

Probing conformational changes in neurotransmitter transporters: a structural context.

The Na+/Cl-dependent neurotransmitter transporters, a family of proteins responsible for the reuptake of neurotransmitters and other small molecules from the synaptic cleft, have been the focus of intensive research in recent years. The biogenic amine transporters, a subset of this larger family, are especially intriguing as they are the targets for many psychoactive compounds, including cocaine and amphetamines, as well as many antidepressants. In the absence of a high-resolution structure for any transporter in this family, research into the structure-function relationships of these transporters has relied on analysis of the effects of site-directed mutagenesis as well as of chemical modification of reactive residues. The aim of this review is to establish a structural context for the experimental study of these transporters through various computational approaches and to highlight what is known about the conformational changes associated with function in these transporters. We also present a novel numbering scheme to assist in the comparison of aligned positions between sequences of the neurotransmitter transporter family, a comparison that will be of increasing importance as additional experimental data is amassed.

Characterization of a functional bacterial homologue of sodium-dependent neurotransmitter transporters.

The tnaT gene of Symbiobacterium thermophilum encodes a protein homologous to sodium-dependent neurotransmitter transporters. Expression of the tnaT gene product in Escherichia coli conferred the ability to accumulate tryptophan from the medium and the ability to grow on tryptophan as a sole source of carbon. Transport was Na(+)-dependent and highly selective. The K(m) for tryptophan was approximately 145 nm, and tryptophan transport was unchanged in the presence of 100 microM concentrations of other amino acids. Tryptamine and serotonin were weak inhibitors with K(I) values of 200 and 440 microM, respectively. By using a T7 promoter-based system, TnaT with an N-terminal His(6) tag was expressed at high levels in the membrane and was purified to near-homogeneity in high yield.

Efficient Synthesis of Functionalized [7]Helicenes.

[7]Helicenebisquinones can be made easily and in quantity by reacting the silyl enol ethers of a 9,10-dialkoxy-, or better a 9,10-disiloxy-, 3,6-diacetylphenanthrene, with p-benzoquinone. If an ethyl enol ether is used in place of the silyl enol ether, the transformation proceeds in much lower yield. The [7]helicenes are efficiently resolved into their enantiomers, and absolute configurations are assigned.