RETINAL FINDINGS IN PRESUMED INFECTIOUS POSTERIOR UVEITIS AND CORRELATION WITH POLYMERASE CHAIN REACTION RESULTS.

PURPOSE: To correlate demographics, retinal lesion characteristics, and host immune status with the pathogen found on polymerase chain reaction analysis of aqueous fluid in patients with suspected infectious posterior uveitis. METHODS: Medical records of patients who underwent anterior chamber paracentesis for suspected infectious posterior uveitis and had retinal photographs between 2014 and 2016 at a single institution were reviewed. Data collection included demographics, clinical appearance of the lesions, and polymerase chain reaction results. Fundus photographs were evaluated by two masked observers for the clinical features of the retinitis. RESULTS: Twenty-eight patients were included in the study. There was substantial to almost perfect agreement on retinitis location (κ = 0.67) and number (κ = 0.76) between the masked photograph graders. Polymerase chain reaction results were positive for herpes simplex virus or varicella zoster virus in 43%, cytomegalovirus in 11%, and toxoplasmosis in 3%; 43% had negative polymerase chain reaction results. Detection of herpes simplex virus or varicella zoster virus on polymerase chain reaction of the aqueous was associated with paucifocal lesions (82%, P = 0.021) and lesions involving the peripheral retina (91%, P = 0.023), consistent with the diagnosis of acute retinal necrosis. CONCLUSION: These data suggest that the diagnosis of acute retinal necrosis can be reasonably inferred on clinical examination, providing a guide for initial empiric therapy.

Exogenous cryptococcal endophthalmitis in an immunocompetent patient.

We describe a case of exogenous cryptococcal endophthalmitis without central nervous system (CNS) involvement or systemic infection in an immunocompetent patient. An 82-year-old male with hypertension, hyperlipidemia, type 2 diabetes mellitus, and primary open-angle glaucoma with a history of left eye trabeculectomy presented with 3 months of worsening left eye pain and redness. Vitreous cultures resulted as Cryptococcus, prompting treatment with intravitreal amphotericin and further investigation. Systemic workup was unrevealing for an endogenous source, CNS involvement, or immunocompromising conditions. He was treated with an aggressive regimen of systemic antifungals, leading to subjective improvements in clinical exam and in vision.

"Persistence of Memory" - Multimodal imaging of delayed sympathetic ophthalmia.

Purpose: To describe a case of late post-surgical sympathetic ophthalmia documented with multimodal imaging. Observations: A 74-year-old male presented to the urgent care of the New York Eye and Ear Infirmary with blurry vision and discomfort in his left eye for three weeks. His vision was 20/50, with intraocular pressure of 13 mmHg, and slit lamp examination was significant for conjunctival congestion, 1+ anterior segment cell and flare, and diffuse keratic precipitates. His right eye was no light perception with a condensed hyphema, intraocular lens and inferonasal tube. His medical history included coronary artery bypass, prostate cancer, hyperlipidemia, and hypertension. His ocular history included blunt trauma to the right eye at age 11 with development of a traumatic macular hole and later rhegmatogenous retinal detachment at age 53, repaired with multiple vitreoretinal procedures. He developed glaucoma in the right eye and was treated with a tube shunt and ultimately transscleral cyclophotocoagulation (TSCPC) 7 years later, 13 years prior to his presentation of the left eye. Dilated fundus examination of his left eye revealed diffuse chorioretinal folds in the macula without any discrete chorioretinal lesions. Ultrasound of the right showed serous macular detachments with scleral thickening. Presumptive diagnosis of sympathetic ophthalmia was made and oral corticosteroid therapy was initiated. Subsequent SD-OCT and en-face OCT-A demonstrated Dalen-Fuchs nodules within the macula underlying areas of resolved serous detachment, after 6 weeks of oral steroids and initiation of immunomodulatory therapy (IMT). Conclusions: Sympathetic ophthalmia may rarely present with very delayed onset, and TSCPC is an uncommon inciting event. These patients may develop serous detachment, choroidal folds and inflammatory nodules identifiable on exam and multimodal imaging, which can resolve when treated appropriately. OCT-A may provide utility in monitoring response to immunosuppressive treatment in these patients.

Bevacizumab (avastin) and ranibizumab (lucentis) for choroidal neovascularization in multifocal choroiditis.

BACKGROUND: Multifocal choroiditis (MFC) is an inflammatory condition, occasionally associated with choroidal neovascularization (CNV). Bevacizumab (Avastin) and ranibizumab (Lucentis) are therapies that target vascular endothelial growth factor. Bevacizumab and ranibizumab have been used successfully to treat CNV in age-related and myopic macular degeneration. PURPOSE: : To describe the treatment of MFC-associated CNV with intravitreal bevacizumab and/or ranibizumab. DESIGN: Retrospective interventional case series. PARTICIPANTS: Six eyes of five patients with MFC-associated CNV were treated with intravitreal bevacizumab and/or ranibizumab. MAIN OUTCOME MEASURES: Visual acuity at 1, 3, and 6 months after the initial injection. RESULTS: Previous therapies (number of eyes treated) included sub-Tenon's corticosteroids (2), intravitreal corticosteroids (1), photodynamic therapy (1), and thermal laser (1). The mean number (range) of antivascular endothelial growth factor injections per eye was 2.3 (1-6). The mean duration (range) of follow-up per patient was 41.5 (25-69) weeks. Five of six eyes improved to 20/30 acuity or better at 6 months. One eye suffered a subfoveal rip of the retinal pigment epithelium with 20/400 acuity. There was a qualitative decrease in clinical and angiographic evidence of CNV. CONCLUSIONS: Bevacizumab and ranibizumab were effective at improving visual acuity over 6 months in a small series of patients with MFC-associated CNV. Tears of the retinal pigment epithelium may occur after intravitreal antivascular endothelial growth factor therapy in MFC-associated CNV.

Are the Current Recommendations for Chloroquine and Hydroxychloroquine Screening Appropriate?

Hydroxychloroquine and quinacrine are frequently used to treat rheumatic diseases. Ocular toxicity, although infrequent, is one of the potential side effects of antimalarial therapies. Current recommendations are unifocal in being developed by only ophthalmologists who do not treat patients for their rheumatic diseases. The data used to create the recommendations are meager and retrospective. Comanagement of patients with rheumatic disease who are exposed to antimalarial therapies requires a greater interaction between ophthalmologists and rheumatologists.

A Case of Corneal Neovascularization Misdiagnosed as Total Limbal Stem Cell Deficiency.

PURPOSE: To report a case of corneal neovascularization misdiagnosed as total limbal stem cell deficiency (LSCD). METHODS: This is a case report of a 61-year-old woman who has a history of bilateral idiopathic scleritis, keratitis, and uveitis for more than 20 years. She was diagnosed with total LSCD in her left eye based on clinical presentation alone and was confirmed as a candidate for limbal transplantation at several major tertiary eye care centers in the United States. After referral to the Stein Eye Institute, in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) were performed to clarify the diagnosis. RESULTS: Slit-lamp examination of the left eye revealed 360-degree severe thinning at the limbus and peripheral corneal pannus and neovascularization that spared the central cornea, a smooth epithelium without fluorescein staining at the central cornea, an uneven surface, and pooling of fluorescein at the peripheral cornea accompanied by minimal fluorescein staining of the sectoral peripheral epithelium. IVCM showed that epithelial cells in the central cornea exhibited a corneal phenotype and that the morphology of the epithelium in all limbal regions except the nasal limbus was normal. Epithelial cellular density and thickness were within the normal range. AS-OCT showed severe thinning in the limbus and a normal epithelial layer in the cornea and limbus. Based on the findings of IVCM and AS-OCT, we concluded that the patient had minimal LSCD, and limbal stem cell transplantation was not recommended. CONCLUSIONS: Clinical presentation alone is insufficient to correctly diagnose LSCD in complex cases. Additional diagnostic tests, such as IVCM, are necessary to confirm the diagnosis before any surgical intervention.

Giant sarcoid tumor of the iris and ciliary body.

PURPOSE: To report the occurrence of a giant iridociliary sarcoid tumor. METHODS: The patient was evaluated by medical history, ophthalmoscopic examination (including photography and ultrasonography) as well as systemic, hematologic, and radiographic examinations. Tumor biopsies allowed for cytopathologic, histopathologic, and immunohistochemical analysis. RESULTS: The 39-year-old black male was found to have a right iris and ciliary body tumor. Ultrasonography revealed a 10 x 12-mm base, 5.6-mm height, low internal reflectivity, and vitreous debris. Radiographic imaging revealed mediastinal and bilateral hilar lymphadenopathy. A purified protein derivative (PPD) and a hematologic survey were negative. Pathology evaluations of the surgical specimens revealed features of non-caseating granulomata consistent with sarcoidosis. A combination of topical and systemic steroid therapy was locally curative. CONCLUSIONS: We describe a giant iridociliary sarcoid tumor in a patient with no lacrimal gland enlargement, conjunctival nodules, or skin lesions. A biopsy was required to establish the diagnosis.

Spontaneous Dissociation of Fluocinolone Acetonide Sustained Release Implant (Retisert) with Dislocation into the Anterior Chamber.

PURPOSE: To report two cases of spontaneous Retisert implant dissociation with dislocation of the medication reservoir into the anterior chamber. DESIGN AND METHODS: Case reports. RESULTS: Two patients with chronic, noninfectious uveitis following Retisert implantation between 6 and 7 years prior presented with a complaint of a "white spot" in their right eyes. Both patients had previous pars plana vitrectomies. Anterior segment examination revealed a dislocated medication reservoir of the Retisert implant in the inferior portion of anterior chamber with associated reservoir-corneal endothelial touch and stromal edema. The reservoirs were subsequently retrieved via a pars plana approach and removed from the anterior chamber through a corneal incision. CONCLUSIONS: Spontaneous dissociation of the Retisert implant with dislocation of the medication reservoir into the anterior chamber can be a late complication of Retisert implantation. Eye care professionals and patients should be aware of this complication, particularly with long-term intraocular retention of this device.

CHIKUNGUNYA-ASSOCIATED UVEITIS AND EXUDATIVE RETINAL DETACHMENT: A CASE REPORT.

PURPOSE: To report the first known case of bilateral granulomatous panuveitis secondary to chikungunya fever in the United States, acquired by a U.S. citizen traveling from an endemic region. METHODS: Case report. RESULTS: A 47-year-old woman presented with 10 days of bilateral decreased vision and photophobia concurrent with a febrile illness contracted while visiting the Dominican Republic. She presented with bilateral granulomatous panuveitis and exudative retinal detachments. Extensive workup was negative with the exception of positive chikungunya virus immunoglobulin G and immunoglobulin M titers. Initially, she responded to corticosteroid treatment but developed recurrent inflammation 3 months after completing the initial treatment. Immunomodulatory therapy was initiated at the time of recurrence, and with immunomodulatory therapy alone her inflammation has been controlled for 6 months. CONCLUSION: The prevalence of chikungunya fever-related uveitis is increasing with the recent epidemics throughout the Americas. Inflammation can occur during the febrile illness or months later and can manifest in a variety of ways. Posterior segment inflammation is more commonly a delayed presentation. Previous reports suggest that chikungunya fever-related uveitis responds well to corticosteroid therapy. This is the first reported case of recurrent inflammation. Given the wide variety of presentations, chikungunya fever-related uveitis should be included in the differential diagnosis of all at-risk patients presenting with acute ocular inflammation, particularly those traveling from endemic regions.

Panuveitis With Exudative Retinal Detachments After Vaccination Against Human Papilloma Virus.

A 20-year-old white woman presented with bilateral acute visual loss (visual acuity: 20/60), panuveitis, and exudative retinal detachments 3 weeks after a second dose of quadrivalent human papillomavirus (HPV4) vaccine. She was treated with oral prednisolone for 6 weeks and responded rapidly. By week 4, vision had normalized and clinical signs resolved. Uveitis after HPV4 vaccination has been reported in two cases. Although the differential diagnosis includes Harada disease, temporal correlation with HPV4 and definitive response to a short course of treatment implicate the vaccine in this case. Vaccine-induced uveitis is rare and difficult to distinguish from coincidental autoimmune disease.

Intraocular lens tolerance in surgery for cataracta complicata: assessment of four implant materials.

PURPOSE: To evaluate various available intraocular lenses (IOL) (PMMA, acrylic, heparin coated PMMA, and silicone) in patients with cataracta complicata and evaluate IOL tolerance, post-operative inflammation, cystoid macular edema, and posterior capsular opacification(PCO) requiring Nd:YAG capsulotomy. DESIGN: randomized, double masked clinical trial. PARTICIPANTS: Patients evaluated in the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary and deemed to need cataract surgery by standard criteria were asked to participate in the clinical trial. Patients had to have a diagnosis of chronic uveitis, which was inactive for 3 months prior to cataract surgery. RESULTS: Acrylic lenses appeared to provide the best overall results when evaluated for post-operative inflammation, PCO rates, visual acuity, and cystoid macular edema (CME) (compared to PMMA, silicone, and heparin coated PMMA).

Polychromatic angiography for the assessment of VEGF-induced BRB dysfunction in the rabbit retina.

PURPOSE: To determine the utility of polychromatic angiography (PCA) in the assessment of VEGF-induced blood retinal barrier (BRB) dysfunction in rabbits. METHODS: Twenty-six eyes of 24 Dutch Belted rabbits were injected intravitreally with 1.25 µg (group A, n = 5), 10 µg (group C, n = 7), or 4 µg (group B, n = 6; group D, n = 4; and group E, n = 4) of VEGF on day 0. Groups D and E were also injected intravitreally with 1.25 µg and 12.5 µg bevacizumab, respectively, on day 2. On days 0, 2, 4, 7, 11, and 14, PCA was performed using a contrast agent mixture composed of fluorescein sodium, indocyanine green, PCM102, and PCM107 and imaged with a modified fundus camera. PCA scores were based on detected leaking fluorophores. RESULTS: On day 7, there was a statistically significant difference between PCA scores of group A (0.6 ± 0.89) and both groups B (2.67 ± 1.37, P = 0.0154) and C (3.33 ± 0.52, P = 0.00085). There was also a statistically significant difference between groups B and E (PCA score 0.75 ± 0.96, P = 0.032) on day 7. On day 11, there was statistically significant difference between group C (1.80 ± 1.1) and both groups A (0, P = 0.021) and B (0.33 ± 0.52, P = 0.037). CONCLUSIONS: A differential response to both increasing VEGF dose and administration of bevacizumab could be discerned using the PCA. PCA allowed stratification of VEGF-induced BRB dysfunction and inhibitory effects of bevacizumab therapy in the rabbit retina.

Fundus image diagnostic agreement in uveitis utilizing free and open source software.

OBJECTIVE: To assess the adequacy of image agreement regarding uveitis based on color fundus and fluorescein angiography images alone, and to use free and open source applications to conduct an image agreement study. DESIGN: Cross-sectional agreement study. PARTICIPANTS: Baseline fundus and fluorescein images of patients with panuveitis, posterior, or intermediate uveitis enrolled in the Multi-center Uveitis Steroid Treatment (MUST) trial. METHODS: Three fellowship-trained specialists in uveitis independently reviewed patient images using ClearCanvas™ and responded using Epi Info™. The diagnoses of the 3 reviewers were compared with the MUST clinician as a gold standard. A rank transformation adjusted for the possible variation in number of responses per patient. Chance-corrected interobserver agreement among the 3 reviewers was estimated with the ι coefficient. Confidence interval (CI) and SE were bootstrapped. RESULTS: Agreement between the diagnoses of the respondents and the baseline MUST clinician's diagnosis was poor across all diagnostic categories, ι = 0.09 (95% CI, 0.07-0.11). The agreement among respondents alone also was poor, ι = 0.11 ± 0.02 (95% CI, 0.08-0.13). The specialists requested more patient historical and clinical information to make a diagnosis on all patients. CONCLUSIONS: The role in distinguishing the multiple conditions in uveitis appears to be limited when based on fundus imaging alone. Future studies should investigate different categories of clinical data to supplement image data. Freely available applications have excellent utility in ophthalmic imaging agreement studies.

Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis.

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

Seronegative spondyloarthropathies and the eye.

PURPOSE OF REVIEW: Ocular inflammation is a common and important manifestation of disease in patients with seronegative spondyloarthropathy. RECENT FINDINGS: Anterior uveitis is among the most common manifestations of eye disease in patients with seronegative spondyloarthropathies. Additionally, a strong correlation exists among such affected patients and the presence of the HLA-B27 gene. Steroid treatment is often effective for uveitis associated with spondyloarthropathies. Patients with ocular inflammation that is chronic in nature or uncontrolled by steroid treatment have shown good response to immunosuppressive agents known to be effective for articular inflammation, such as methotrexate. Recent studies have shown the possible benefits of tumor necrosis factor-alpha inhibitors, such as infliximab and etanercept. SUMMARY: Uveitis, a leading cause of blindness, is among the most common eye manifestations in patients affected by seronegative spondyloarthropathies. Evidence suggests both genetic and environmental factors in its pathogenesis. Immunomodulator treatments, including the recently popular biologics, may be effective in the control of chronic uveitis in patients with spondyloarthropathy. Ocular surgery is often needed in these patients, and appropriate cautions are required in order to achieve successful vision rehabilitation.

Limbal stem cell transplantation in chronic inflammatory eye disease.

OBJECTIVE: The goal of this study was to describe the outcome of limbal stem cell transplantation (LSCT) in patients with severe ocular surface disease caused by underlying chronic inflammatory eye disease. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Nine patients with limbal stem cell deficiency caused by an underlying ocular inflammatory disease who underwent LSCT. METHODS: The authors reviewed the records of 11 eyes of 9 patients with immunologically mediated ocular surface disease that underwent LSCT. MAIN OUTCOME MEASURES: The main outcome measures were reepithelialization of the corneal surface, restoration of corneal surface, and improvement in visual acuity. RESULTS: A total of 11 eyes underwent either autologous (n = 1) or HLA-matched living related donor (n = 10) LSCT for ocular surface disease secondary to inflammatory disease. Reepithelialization of the corneal surface in the immediate postoperative period occurred in 10 eyes (91%) within an average of 10 days (range, 3-21 days). Long-term restoration of the corneal surface was achieved in six (55%) eyes. Visual acuity improved in six eyes (55%). Reasons for poor outcomes included microbial infection, limbal stem cell graft rejection, and corneal ulceration. No donor eyes had complications. CONCLUSIONS: Patients with underlying immunologically mediated diseases, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or ocular cicatricial pemphigoid, who undergo LSCT have lower success rates than do those patients with noninflammatory ocular surface diseases.

Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy.

PURPOSE: To determine whether electroretinogram results can help predict the success in tapering of immunosuppressive medication in patients with birdshot retinochoroidopathy. METHODS: Fifteen patients with birdshot retinochoroidopathy who had at least three serial electroretinograms (ERG) during the course of their disease were included in the study. Charts of patients seen at the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts were retrospectively reviewed. Seven parameters of the ERGs were examined: dim scotopic amplitude, bright scotopic amplitude, bright scotopic implicit time, single-flash photopic amplitude, single-flash photopic implicit time, 30 Hz flicker amplitudes, and 30 Hz flicker implicit times. For each parameter the patients were divided into two groups, those with normal and those with abnormal responses at the time their immunosuppressive medication taper was initiated. The percentage of patients in each group who were able to successfully taper their immunosuppressive medication was calculated. A successful taper of medication was defined as no recurrence of disease signs or symptoms for at least 1 year after the medication was terminated. RESULTS: Abnormalities in the bright scotopic response amplitudes and 30 Hz flicker implicit times were associated with recurrence of inflammation as immunosuppressive therapy was tapered. CONCLUSION: ERG can serve as a useful adjunct in helping determine when to initiate tapering of immunosuppressive therapy in patients with birdshot retinochoroidopathy.