Repeat Conjunctival Biopsy after Immunomodulatory Therapy for Ocular Mucous Membrane Pemphigoid.

PURPOSE: To evaluate whether conjunctival biopsy findings in patients with ocular mucous membrane pemphigoid (MMP) persist as positive or revert to negative following treatment with immunomodulatory therapy (IMT). METHODS: Patients with biopsy-proven MMP were treated with IMT for at least 2 years before undergoing repeat conjunctival biopsy for immunofluorescence microscopy. Their records were reviewed and findings evaluated to ascertain which patients' biopsies showed antibody deposition on the conjunctival basement membrane. RESULTS: Following 2 years of IMT, conjunctival biopsies showed persistent antibody deposition in two patients, and were negative in four patients. CONCLUSIONS: Conjunctival biopsies in patients with ocular MMP may show reversion to inactive disease following IMT. Post-treatment biopsy might be clinically useful as a means of evaluating the efficacy of therapy in this chronic disease.

Routes for Drug Delivery: Sustained-Release Devices.

Several different technologies exist for sustained-release drug delivery devices, including: (1) nonbiodegradable implants; (2) biodegradable implants; (3) micro- and nanoparticles; (4) liposomes, and (5) encapsulated cell technology (ECT). Currently, the only sustained-release devices approved by the Food and Drug Administration are the ganciclovir implant for the treatment of cytomegalovirus retinitis, the fluocinolone acetonide implant for the treatment of noninfectious posterior uveitis and the dexamethasone implant for the treatment of diabetic macular edema or noninfectious posterior uveitis. The first two implants are nonbiodegradable and require surgical placement, whereas the dexamethasone implant is biodegradable, and can be shaped and injected using a small-gauge needle or applicator into the vitreous. ECT, currently in a phase II clinical trial, utilizes modified retinal pigment epithelium cells to produce protein drug molecules in the vitreous. The microparticle, nanoparticle and liposome technology currently in development may offer the most flexibility for prolonged drug release and combination therapy for retinal diseases.

Central retinal vein occlusion resulting from anomalous retinal vascular anatomy in a 24-year-old man.

An otherwise healthy 24-year-old man presented with a painless decrease of vision in the left eye for 2 days. Best-corrected visual acuity was 20/20 in the right eye and 20/80 in the left eye. Anterior exam was unremarkable and funduscopic exam in the left eye revealed retinal hemorrhages in all four quadrants with venous dilation and tortuosity consistent with central retinal vein occlusion. Fluorescein angiography revealed delayed venous filling with neither leakage nor vasculitis. A comprehensive work-up that included infectious, inflammatory, and hypercoagulability studies was unremarkable, and magnetic resonance imaging of the orbits was unrevealing. After 2 months, best-corrected visual acuity returned to 20/20-2 in the left eye. Upon closer review of the vascular anatomy in the left eye, a bifurcation of the central retinal artery at the level of the optic disc was tightly intertwined with an undilated nasal retinal vein in a manner that appeared to compress the underlying central retinal vein, resulting in dilation and tortuosity of the remaining venous branches. The vessel wall damage, turbulent venous flow, and compressive mass effect resulting from the anomalous retinal vasculature relationship is the proposed mechanism of the central retinal vein occlusion. Careful attention to the retinal vascular anatomy is suggested to aid in assessing the risk of retinal vein occlusion in any age group.

Quality of Life in Patients with Noninfectious Uveitis Treated with or without Systemic Anti-inflammatory Therapy.

PURPOSE: To compare vision-related (VR-QOL) and health-related quality of life (HR-QOL) in patients with noninfectious uveitis treated with systemic anti-inflammatory therapy versus nonsystemic therapy. METHODS: A prospective, cross-sectional study design was employed. VR-QOL and HR-QOL were assessed by the 25-Item Visual Function Questionnaire (VFQ-25) and the Short Form 12-Item Health Survey (SF-12), respectively. Multivariate regression analysis was performed to assess the VR-QOL and HR-QOL based on treatment. RESULTS: Among the 80 patients, the median age was 51 years with 28 males (35%). The adjusted effect of treatment modality on VR-QOL or HR-QOL showed no statistically significant difference in all subscores of VFQ-25 or physical component score (PCS) and mental component score (MCS) of SF-12. Systemic therapy did not compromise VR-QOL or HR-QOL compared to nonsystemic therapy. CONCLUSIONS: Systemic therapy can be effectively used to control serious cases of noninfectious uveitis without significant relative adverse impact on quality of life.

HIPAA for physicians in the information age.

The increased prominence of electronic health records, email, mobile devices, and social media has transformed the health care environment by providing both physicians and patients with opportunities for rapid communication and knowledge exchange. However, these technological advances require increased attention to patient privacy under the Health Insurance Portability and Accountability Act (HIPAA). Instant access to large amounts of electronic protected health information (PHI) merits the highest standard of network security and HIPAA training for all staff members. Physicians are responsible for protecting PHI stored on portable devices. Personal, residential, and public wireless connections are not certified with HIPAA-compliant Business Associate Agreements and are unsuitablefor PHI. A professional and privacy-oriented approach to electronic communication, online activity, and social media is imperative to maintaining public trust in physician integrity. As new technologies are integrated into health care practice, the assurance of privacy will encourage patients to continue to seek medical care.

Aflibercept in the treatment of neovascular age-related macular degeneration in previously treated patients.

PURPOSE: To study the visual outcomes and change in central macular thickness (CMT) in patients with neovascular age-related macular degeneration (AMD) who were previously treated with ranibizumab (Lucentis) and/or bevacizumab (Avastin) and were subsequently switched to aflibercept (VEGF Trap-Eye; Eylea). METHODS: Retrospective study of patients who received intravitreal aflibercept from December 2011 to December 2012 and had previous anti-vascular endothelial growth factor treatment for AMD. The main outcome measures were best-corrected visual acuity (BCVA) and CMT as measured by optical coherence tomography. RESULTS: The study population included 30 patients aged 80.4±1.45 (mean±SEM) who received 6.27±0.37 (range 4-11) aflibercept injections. Eighteen patients had previously received only bevacizumab (12.4±2.18 injections), 2 had received only ranibizumab (19±6 injections), and 10 had received both ranibizumab and bevacizumab (mean 19.3 injections). BCVA logMAR at the initial visit (aflibercept initiation) was 0.506±0.054 (mean VA 20/64), and then, follow ups at 1-month 0.504±0.055 (20/64) P=0.903, 3-months 0.458±0.061 (20/57) P=0.112, 6-months 0.413±0.071 (20/52) P=0.036, and 12-months 0.521±0.076 (20/66) P=0.836. CMT at the initial visit was 261±10.9, and then, at 1-month 238±12.4 P=0.021, 3-months 245±10.6 P=0.102, 6-months 245±10.4 P=0.099, and 12-months 237±10.2 P=0.012. Results were similar in a subset of patients (n=15) with central macular edema or submacular fluid at aflibercept initiation. While on aflibercept, 2 patients developed intraocular pressure increases that required treatment. CONCLUSIONS: These findings demonstrate a significant decrease in CMT but no statistically significant improvement in BCVA through the 12-month follow up in patients previously treated who were switched to aflibercept for AMD. Patients may develop ocular hypertension after multiple aflibercept injections.

5-Fluorouracil for epithelial downgrowth after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report the use of intracameral 5-fluorouracil (5-FU) to treat epithelial downgrowth after performing a Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: We describe the case of a 79-year-old woman who underwent a DSAEK for pseudophakic Fuchs endothelial corneal dystrophy. The patient required 2 repeat DSAEKs for graft failure and persistent, visually significant interface haze. Six months after the third and most recent DSAEK, the patient was followed up and found to have a visual acuity of 20/100. On examination, the patient continued to have a persistent interface haze. However, the patient also had a cellular anterior chamber reaction despite the administration of frequent topical corticosteroids, and subtle findings of a translucent, membranous growth over the iris. Argon laser photocoagulation of the area resulted in a whitening response, characteristic of epithelial growth. RESULTS: Epithelial downgrowth was diagnosed, and intracameral 5-FU was administered. One month after the injection was given, the patient's examination results and vision improved to 20/60. Six months after the single injection, the patient had a clear DSAEK graft without interface haze, a quiet chamber, and 20/30 visual acuity. CONCLUSIONS: Epithelial downgrowth that occurs after performing a DSAEK can be treated successfully using intracameral 5-FU.

Necrobiotic xanthogranuloma and chronic lymphocytic leukemia of the conjunctiva masquerading as scleritis and uveitis.

This report describes a unique case of coexisting necrobiotic xanthogranuloma and chronic lymphocytic leukemia in a patient presenting with scleritis and uveitis. A 53-year-old Caucasian man diagnosed with anterior uveitis and scleritis for the prior year was referred to our uveitis clinic for further evaluation. Prior uveitis/scleritis workup performed by the referring ophthalmologist was negative. Examination demonstrated unilateral uveitis and posterior scleritis along with bilateral conjunctival lesions. Incisional biopsy of the conjunctiva was carried out. The excised tissue was sent fresh for histopathologic studies. Slit-lamp examination revealed bilateral yellow-white bulbar conjunctival lesions, 1+ conjunctival injection OU, stellate keratic precipitates OS with 25 cells per high-powered field. Funduscopic examination was significant for subretinal fluid OS. Conjunctival biopsy revealed necrobiotic xanthogranuloma and chronic lymphocytic leukemia. Systemic workup demonstrated paraproteinemia consistent with necrobiotic xanthogranuloma and a complete blood count consistent with leukemia. This case demonstrates an atypical presentation of necrobiotic xanthogranuloma and concomitant chronic lymphocytic leukemia presenting in the form of uveitis, scleritis, and conjunctival infiltration. Masquerade syndromes, such as necrobiotic xanthogranuloma and leukemia, must be kept in mind when treating patients with uveitis or scleritis with negative workups.

Ocular manifestations of systemic inflammatory diseases.

Inflammation of the eye is often times seen in association with systemic inflammatory diseases. Understanding the various forms of ocular involvement in these conditions is important as untreated ophthalmic involvement can lead to severe vision loss. In addition to providing a basic framework for diagnosis and treatment, this review will highlight the ocular manifestations of the following systemic inflammatory conditions: rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, Sjögren's syndrome, polyarteritisnodosa, primary antiphospholipid syndrome, Behçet's syndrome, Kawasaki disease, Cogan's syndrome and relapsing polychondritis.

Telemedicine-based digital retinal imaging vs standard ophthalmologic evaluation for the assessment of diabetic retinopathy.

OBJECTIVE: To study the cost benefit analysis of using a telemedicine-based digital retinal imaging evaluation compared to conventional ophthalmologic fundus examination of diabetic patients for diabetic retinopathy. METHODS: In this study, diabetic patients from Community Health Center, Inc. (CHCI), a large multi-site Federally Qualified Health Center) were evaluated by teleophthalmology using the Canon CR-1 nonmydriatic fundus camera. Digital images were acquired in the CHCI offices and saved on the EyePACS server network. The images were later evaluated by retinal specialists at the Yale Eye Center, Yale University Department of Ophthalmology and Visual Science. The costs for the standard of care ophthalmic examinations were calculated based on 2009 Medicaid reimbursement rates. The process of telemedicine-based diagnosis was based on a take-store-forward-visualize system. The cost of telemedicine-based digital retinal imaging examination included cost for devices, training, annual costs and a transportation fee. Current Medicaid reimbursement, transportation, and staff labor costs were used to calculate the conventional retinal examination cost as a comparison. RESULTS: Among the 611 patients digital retinal images screened in the first year of this program and for whom data are available, 166 (27.2%) cases of diabetic retinopathy were identified. Seventy-five (12.3%) patients screened positive with clinically significant disease and were referred for further ophthalmological evaluation and treatment. The primary direct cost of the telemedicine was $3.80, $15.00, $17.60, $1.50, and $2.50 per patient for medical assistant, ophthalmologist, capital cost (Equipment + Training), equipment maintenance, and transportation fee, respectively. The total cost in the telemedicine-based digital retinal imaging and evaluation was $40.40. The cost of conventional retinal examination was $8.70, $65.30, and $3.80 per patients for round-trip transportation, 2009 national Medicaid Physician Fee Schedule allowable for bilateral eye examination, and medical assistant personnel, respectively. The total costs of conventional fundus examination were $77.80. An additional conventional ophthalmologic retinal examination was required for 75 (12.3%) patients with clinically significant disease on telemedicine evaluation, which involves an averaged additional cost of $ 9.55 per patient for all the patients in the study. If the cost of subsequent examination was added, the total cost of telemedicine-based digital fundus imaging was $49.95 per patient in our group of 611 patients evaluated. CONCLUSIONS: Our cost analysis indicates that telemedicine-based diabetic retinopathy screening cost less ($49.95 vs $77.80) than conventional retinal examination and the telemedicine-based digital retinal imaging examination has the potential to provide an alternative method with greater convenience and access for the remote and indigent populations. Diabetes mellitus and diabetic retinopathy are growing problems in the United States and worldwide. Large scale adoption of telemedicine should be encouraged as a means toward providing improved access, increasing compliance with annual evaluation, at a low cost for patients with diabetes with direct access to an eye care specialist.

Effects of music therapy on intravitreal injections: a randomized clinical trial.

PURPOSE: To investigate the effects of music therapy on anxiety, perceived pain, and satisfaction in patients undergoing intravitreal injections in the outpatient setting. METHODS: This is a randomized clinical trial. Seventy-three patients were recruited from the retina clinic at 1 institution and randomized into a music therapy (n=37) or control (n=36) group. Prior to injection, patients completed the state portion of the Spielberger State Trait Anxiety Inventory (STAI-S). The music therapy group listened to classical music through computer speakers while waiting for and during the injection. The control group underwent the injection in the same setting without music. Afterward, all patients completed another STAI-S and a satisfaction and pain questionnaire. The main outcome measures were objective anxiety derived from STAI-S scores and subjective pain and anxiety from the post procedure questionnaire. RESULTS: The music therapy group had a greater decrease in anxiety than the control group (P=0.0480). Overall, 73% of all patients requested music for future injections (P=0.0001). The music therapy group (84%) requested music in future injections more frequently than the control group (61%) (P=0.0377). Both groups reported similar levels of pain (P=0.5879). CONCLUSIONS: Classical music before and during intravitreal injections decreases anxiety in patients without decreasing pain. Most patients desire to have music during future injections. Music therapy is a low-cost, easy, safe intervention that reduces anxiety during intravitreal injections in the outpatient setting.

Biological agents for the treatment of uveitis.

INTRODUCTION: The conventional treatment of uveitis includes corticosteroids and immunosuppressive agents, which are highly efficacious, but can be associated with serious systemic side effects. Over the last two decades, advances in the understanding of the pathogenesis of inflammatory diseases, as well as improved biotechnology, have enabled selective targeting of the chemical mediators of diseases. Recently, a new class of drugs called biologics, that target the various mediators of the inflammation cascade, may potentially provide more effective and less toxic treatment. AREAS COVERED: This article is a review and summary of the peer-reviewed evidence for biologic agents in the treatment of various forms of ocular inflammation and it focuses on the potential use of other biologic agents that have been tested in experimental autoimmune uveitis. Pubmed was used as our main tool for our literature search. Some additional references were taken from books written on the subject. EXPERT OPINION: There are a wide variety of new and emerging biological agents currently being used in the treatment of uveitis which has expanded the therapeutic horizons far beyond previous limitations.

Bilateral drug (ipilimumab)-induced vitritis, choroiditis, and serous retinal detachments suggestive of vogt-koyanagi-harada syndrome.

PURPOSE: To report a case of bilateral drug (ipilimumab)-induced vitritis, choroiditis, and serous retinal detachments suggestive of Vogt-Koyanagi-Harada syndrome. METHODS: This is a single case report. RESULTS: A 43-year-old woman with metastatic melanoma reported a 1-day history of blurry vision after starting a phase 1 clinical trial of ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 blocker, 2 weeks before presentation. Fundus examination of both eyes showed bilateral serous detachments with associated vitritis and choroiditis. Optical coherence tomography confirmed the presence of serous detachments, and fluorescein angiography demonstrated multiple areas of pinpoint leakage at the level of the retinal pigment epithelium. Treatment with high-dose corticosteroids led to a rapid improvement in vision and resolution of her serous detachments. Ten weeks after initial presentation, the patient developed vitiligo and poliosis. CONCLUSION: Vogt-Koyanagi-Harada syndrome is a bilateral granulomatous panuveitis associated with dermatologic, neurologic, and audiologic manifestations of yet an unclear pathogenesis. To our knowledge, we report the first case of ipilimumab treatment resulting in the acute presentation of bilateral vitritis, choroiditis, and serous detachments suggestive of Vogt-Koyanagi-Harada syndrome, which has particular significance because it may corroborate previous research attempting to elucidate the underlying mechanism of the disease.

Intraocular metastasis of testicular natural killer T-cell lymphoma with diffuse retinal pigment epithelium changes.

PURPOSE: The purpose of this study was to report the first confirmed case of testicular natural killer T-cell lymphoma with bilateral intraocular metastasis. METHODS: The author presents a chart review of a patient with testicular natural killer T-cell lymphoma metastasis to both eyes. This patient was treated with systemic chemotherapy, radiation, and intravitreal injections of methotrexate. RESULTS: The author identified one case of a patient with the diagnosis of bilateral metastatic natural killer T-cell lymphoma with ocular involvement treated with intravitreal methotrexate. After treatment, the patient developed diffuse widespread retinal pigment epithelium alterations in giraffe-like patterns. CONCLUSION: This represents a clinical case of a patient with primary testicular natural killer T-cell lymphoma and ocular metastasis with posttreatment retinal changes resembling bilateral diffuse uveal melanocytic proliferation.

Coats-like response in linear en coup de sabre scleroderma.

PURPOSE: To describe a Coats-like response and central nervous system vasculitis and its successful management in a patient presenting with en coup de sabre scleroderma. METHODS: Retrospective interventional case report. Chart review. RESULTS: A 20-year-old white male patient with en coup de sabre scleroderma on treatment with oral cyclophosphamide and prednisone for associated central nervous system inflammation presented with photopsias in the ipsilateral side of the scleroderma. A magnetic resonance imaging before presentation had shown lesions suggestive of localized central nervous system vasculitis. Ocular examination showed vitritis and multiple venous and arteriolar saccular dilatations with lipid exudation and subretinal fluid. These were treated with intravitreal bevacizumab, focal laser, and subtenon triamcinolone acetonide. After a year of follow-up, there was near resolution of the exudation and complete resolution of the vitreous inflammation, and the patient has been clinically stable with no visual loss. CONCLUSION: Coats-like response with ocular inflammation can be associated with central nervous system vasculitis in patients with linear scleroderma. Careful clinical evaluation and aggressive multipronged treatment are necessary to ensure a successful outcome.

Subretinal fibrosis and uveitis syndrome in a patient with ectodermal dysplasia.

PURPOSE: To report a case of subretinal fibrosis and uveitis syndrome in association with ectodermal dysplasia. METHODS: Chart review of a patient with subretinal fibrosis and uveitis syndrome and ectodermal dysplasia. RESULTS: The authors identified one case of a patient with the diagnoses of subretinal fibrosis and uveitis syndrome and ectodermal dysplasia. CONCLUSIONS: This represents an uncommon case of a patient with the diagnoses of both subretinal fibrosis and uveitis syndrome and ectodermal dysplasia.

Choroiditis in a patient with multiple sclerosis.

PURPOSE: To describe choroiditis in multiple sclerosis (MS). DESIGN: Case report. METHODS: Clinical findings, fluorescein angiography, optical coherence tomography, and treatment are presented. A 50-year-old man with MS presented with vitritis and multiple choroidal lesions in the fovea and periphery in both eyes. Fluorescein angiography (FA) revealed early hyperfluorescence and late leakage of the lesions. Optical coherence tomography showed subretinal fluid in the right eye. One month post-treatment, visual acuity returned to the baseline with complete resolution of subretinal fluid and decreased leakage on FA. CONCLUSIONS: Choroiditis might be related to MS, but may also be a chance occurrence.

Daclizumab for treatment of birdshot chorioretinopathy.

OBJECTIVE: To report the outcomes for daclizumab in the treatment of birdshot chorioretinopathy (BSCR) refractory to traditional immunomodulatory therapy (IMT). METHODS: We retrospectively reviewed medical records of 8 patients with BSCR whose disease was refractory to or who were intolerant of traditional IMT. All patients received 1 mg/kg of daclizumab intravenously at 2-week intervals initially at 1 referral uveitis practice. Main outcome measures were changes in visual acuity, vitreous inflammation, fluorescein angiographic pathologic features, electroretinography (ERG) parameters, concomitant IMT requirements, and adverse events. RESULTS: Over a mean follow-up of 25.6 months, 7 patients had either stabilization or improvement in visual acuity of both eyes and complete resolution of vitreous inflammation. Six patients had resolution of vasculitis on fluorescein angiography. The ERG 30-Hz implicit times and the bright scotopic amplitudes worsened in some patients despite abolition of clinically evident inflammation. Four patients were able to discontinue all other IMT and remain inflammation free while receiving only daclizumab treatment. Two patients developed adverse effects that led to daclizumab treatment discontinuation. CONCLUSIONS: Daclizumab therapy was effective in stabilizing vision and decreasing inflammation in most patients with BSCR. The ERG parameters continued to decline in some patients despite adequate inflammatory control. Regular serologic monitoring is critical to detect adverse events.

Solitary myofibroma of the sclera.

PURPOSE: To report a novel case of solitary myofibroma involving the sclera. METHODS: Case report and review of the literature. RESULTS: A 19-year-old woman had an expanding and painful epibulbar mass clinically diagnosed as nodular scleritis that did not respond to anti-inflammatory therapy. A biopsy showed a proliferation of spindle-shaped cells that reacted strongly positively with immunoperoxidase stains for vimentin and smooth-muscle actin. The diagnosis of solitary myofibroma was made. Six months postoperatively, the patient was well, and the lesion had not recurred. CONCLUSIONS: Myofibroma should be considered in the differential diagnosis of an epibulbar mass, especially in the setting that would mimic nodular scleritis.

Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic syndrome.

Cancer associated retinopathy (CAR) is an uncommon paraneoplastic retinopathy in which antibodies are directed against retinal antigens. Vision loss is associated with abnormal ERG findings. Few case reports and lack of controlled clinical trials make management of this syndrome especially challenging for the clinician. Herein, we describe the clinical, histopathologic and electrophysiologic features of CAR, along with a summary of previously employed management options. Cancer associated retinopathy syndrome has been recognized as a paraneoplastic disorder, most commonly associated with small cell lung cancer, in which cross-reacting autoantibodies against retinal antigen cause retinal dysfunction. Bilateral vision loss as a result of both rod and cone dysfunction in CAR may occur over a period of months, and visual symptoms may precede diagnosis of the systemic malignancy. The heterogeneity in antigens that have been identified as targets of antibody-mediated retinal damage perhaps help to explain the complexity of symptoms and the treatment challenges posed by patients with CAR.