TACROLIMUS FOR IMMUNOSUPPRESSION IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE, POSTERIOR, OR PANUVEITIDES.

PURPOSE: To evaluate the effectiveness of tacrolimus in patients with noninfectious intermediate, posterior, or panuveitis needing a two-immunosuppressive-agent regimen. METHODS: Design: Retrospective cohort study. Setting: Two tertiary-care uveitis practices at academic medical centers. Patient population: Thirty-two patients with noninfectious intermediate, posterior, or panuveitides in whom single-agent immunosuppression was inadequate to effect successful corticosteroid sparing. Intervention: tacrolimus, added as the second immunosuppressive agent. Main outcome measure: successful corticosteroid sparing, defined as inactive uveitis at a dose of prednisone ≤7.5 mg/day. RESULTS: Active uveitis was present in 65.6% of patients at initiation of tacrolimus, and the median time to inactive uveitis was 1.5 months (95% confidence interval 1.2, 4.08). The median time to successful corticosteroid sparing was 3.9 months (95% confidence interval 1.41, 6.67), and by 6 months of follow-up successful corticosteroid sparing was achieved in 75% of patients. Tacrolimus was discontinued for side effects in five patients, three for tremor, and two for hyperglycemia. All side effects were reversible with tacrolimus discontinuation. CONCLUSION: Tacrolimus seems to have efficacy as a second immunosuppressive agent in two-immunosuppressive drug regimens, when a single agent does not permit successful corticosteroid sparing. Side effects were reversible with tacrolimus discontinuation.

Uveitis for Dermatologists: A Review.

Certain dermatologic conditions and drugs used for their treatment are associated with uveitis, a vision-threatening group of inflammatory eye diseases. Dermatologists may therefore be the first healthcare providers to recognize the presence of uveitis in certain patients and can help ensure morbidity is minimized. Posterior uveitis in particular, which may manifest as insidious, painless vision loss, may first be identified by a careful review of systems by a dermatologist. Understanding uveitis and its associations with certain skin findings and drugs will help enable identification and triage of patients in need of ophthalmic care. An overview of uveitis is provided, including its epidemiology, etiologies, classification, presenting signs and symptoms, general management, and complications. Next, dermatologic diseases that may be associated with uveitis are reviewed with a focus on how uveitis is most likely to present. Lastly, drugs used by dermatologists and less common dermatologic diseases associated with uveitis are reviewed. Multidisciplinary management is necessary for patients with both skin disease and ocular complications such as uveitis. Dermatologists’ recognition of uveitis in patients may reduce time to referral and improve patient outcomes. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5165.

Vogt-Koyanagi-Harada disease.

PURPOSE OF REVIEW: The purpose of this article is to review the current literature on Vogt-Koyanagi-Harada (VKH) disease, including current treatment options and new research directions. RECENT FINDINGS: Recent publications on VKH disease show an increased focus on the immunogenetics and immune pathways associated with the development of VKH disease. There have also been advances in imaging modalities and techniques that may help to better elucidate the disease process in eyes with VKH disease. SUMMARY: VKH disease is an autoimmune, multisystem inflammatory disorder, the cause of which is still incompletely understood. Continued research may elucidate the causes and triggers of immune dysregulation in this disease, and in doing so, identify novel therapeutic targets.

Clinical features and incidence rate of ocular complications in punctate inner choroidopathy.

PURPOSE: To study the clinical features and incidence rate of ocular complications in patients with punctate inner choroidopathy. METHODS: This is a retrospective cohort study conducted in a single-center academic practice setting. Patients diagnosed with punctate inner choroidopathy at the Wilmer Eye Institute, Johns Hopkins University from 1984 to 2012 were identified. Demographics and clinical features including the presence of choroidal neovascularization (CNV) and structural complications were collected. Main outcome measures, including visual impairment and incidence rate of ocular complications, were analyzed. RESULTS: Thirty-one patients (59 eyes) were included in the study. Follow-up data were available for 24 patients (47 eyes) with a mean follow-up time of 3.4 years (range, 2 months to 8.7 years). In the affected eyes with follow-up, the incidence rate of visual impairment to 20/50 or worse was 0.06 per eye-year (EY) (95% confidence interval, 0.022/EY-0.114/EY). The incidence rate of visual loss to 20/200 or worse was 0.006/EY (95% confidence interval, 0.0001/EY-0.034/EY). Thirty-six eyes (77%) had an ultimate visual acuity of 20/40 or better. All of the 13 patients with more than ≥ 3 years of follow-up had a visual acuity of ≥ 20/40 in at least 1 eye at 3 years after presentation. Two thirds of the follow-up patients (67%) on immunomodulatory drug therapy did not have new or recurrent CNV. However, this was not a statistically significant difference. Three eyes with follow-up had recurrence of CNV for an incidence rate of 0.04/EY (95% confidence interval, 0.008/EY-0.12/EY). Two eyes developed new CNV during follow-up for an incidence rate of 0.02/EY (95% confidence interval, 0.002/EY-0.066/EY). CONCLUSION: The visual prognosis in most cases of punctate inner choroidopathy is very good. The incidence rate of new CNV and recurrent CNV was 0.02/EY and 0.04/EY, respectively.

Investigating the Accuracy and Completeness of an Artificial Intelligence Large Language Model About Uveitis: An Evaluation of ChatGPT.

PURPOSE: To assess the accuracy and completeness of ChatGPT-generated answers regarding uveitis description, prevention, treatment, and prognosis. METHODS: Thirty-two uveitis-related questions were generated by a uveitis specialist and inputted into ChatGPT 3.5. Answers were compiled into a survey and were reviewed by five uveitis specialists using standardized Likert scales of accuracy and completeness. RESULTS: In total, the median accuracy score for all the uveitis questions (n = 32) was 4.00 (between "more correct than incorrect" and "nearly all correct"), and the median completeness score was 2.00 ("adequate, addresses all aspects of the question and provides the minimum amount of information required to be considered complete"). The interrater variability assessment had a total kappa value of 0.0278 for accuracy and 0.0847 for completeness. CONCLUSION: ChatGPT can provide relatively high accuracy responses for various questions related to uveitis; however, the answers it provides are incomplete, with some inaccuracies. Its utility in providing medical information requires further validation and development prior to serving as a source of uveitis information for patients.

Characterization of autoimmune eye disease in association with Down's syndrome.

BACKGROUND: Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. RESULTS: We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. DISCUSSION: A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

Postoperative outcomes after fluocinolone acetonide implant surgery in patients with birdshot chorioretinitis and other types of posterior and panuveitis.

PURPOSES: To evaluate outcomes after placement of fluocinolone acetonide (FA) implants in eyes with birdshot chorioretinitis and to compare these outcomes with eyes with posterior and panuveitis. METHODS: This is a retrospective cohort study of 48 eyes from patients with posterior and panuveitis treated with FA implants from 2006 to 2010. Outcome measures include visual acuity, intraocular pressure, need for glaucoma surgery, postoperative complications, and control of inflammation. RESULTS: All eyes treated with FA implants achieved improved control of inflammation and decreased reliance on adjunctive therapy. Birdshot chorioretinitis eyes had a statistically significant increase in intraocular pressure in the first 4 months after FA implantation (P = 0.04) compared with baseline intraocular pressure. A higher percentage of eyes with birdshot chorioretinitis required glaucoma surgery and after a shorter time period after FA implantation than did eyes with other forms of posterior and panuveitis (0.42/eye-year vs. 0.11/eye-year; median time to glaucoma surgery: 15.5 months vs. 31.5 months respectively, hazard ratio, 3.4; 95% confidence interval, 1.0-10.8, P = 0.04). CONCLUSION: Although the FA implant is effective in controlling inflammation and reducing the need for systemic immunosuppressive therapy, eyes of patients with birdshot chorioretinitis tend to have a more robust intraocular pressure response to the FA implant than eyes with other types of posterior and panuveitis.

Effectiveness of difluprednate in addition to systemic therapy for the treatment of anterior scleritis.

AIM: To describe the effectiveness and side-effect profile of adding difluprednate therapy to patients with anterior scleritis being treated systemically. METHODS: Retrospective chart review. Charts from all patients with anterior scleritis who were treated with topical difluprednate in addition to systemic therapy from 1 January 2018 to 1 January 2020 were reviewed. Data collected included: demographics, scleritis type, systemic diagnosis, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, type of systemic treatment used, best-corrected visual acuity (BCVA) and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥2 lines, change in lens status or cataract surgery and IOP ≥24 mm Hg. RESULTS: Thirty-two patients (44 eyes) were analysed. The median age was 57 years (IQR 52, 72); 59% were female; 72% were Caucasian. An associated systemic disease was present in 59%. Systemic therapies used when difluprednate was added were: 65% immunosuppressive agents, 43% prednisone and 25% non-steroidal anti-inflammatory drugs. The addition of difluprednate resulted in clinical resolution in 79.6% of the treated eyes. Median time to inactivity was 9 weeks (IQR 5, 20). Eyes initially using 2-4 drops per day had a higher response rate (89%, p=0.005). Over a median follow-up of 34 weeks (IQR 21, 74), 11 eyes had IOP elevation; 6 eyes lost ≥2 lines of BCVA, 5 eyes had cataract progression. CONCLUSION: Most eyes treated with difluprednate achieved inactivity. The addition of difluprednate to systemic therapies provides an alternative to achieve control of inflammation.

Using the Electronic Medical Record to Increase Laboratory Test Monitoring in Ocular Inflammation Patients: A Quality Improvement Study.

BACKGROUND AND OBJECTIVES: Treatment of chronic, noninfectious ocular inflammation includes corticosteroids, disease-modifying antirheumatic medications, and biologics. To mitigate adverse effects associated with the use of these medications, routine laboratory test monitoring is recommended throughout treatment. We evaluated the effectiveness of an alert added to the electronic medical record (EMR) to aid in laboratory test monitoring for patients prescribed these high-risk medications. METHODS: A prospective, interventional study assessed the effect of the alert within the EMR on laboratory test ordering at the Division of Ocular Immunology at the Wilmer Eye Institute. The primary outcome measure was the change in number of ordered laboratory tests at 3, 6, and 12 months after the alert activation compared with pre-intervention levels and overall through the study period. The laboratory tests that were monitored included complete blood count, comprehensive metabolic panel, dual-energy x-ray absorptiometry (DXA) scanning, fasting lipid panel, and interferon gamma release assays. RESULTS: The laboratory test orders for 153 patients on high risk medications were analyzed. Only the frequency of ordering the DXA and interferon gamma release assays increased significantly, compared with baseline, throughout the study. Conversely, there was a significant decrease in the frequency of ordering of fasting lipid profiles and hemoglobin A 1c at each time point and for complete blood count and comprehensive metabolic panel at the 6-month time point. CONCLUSION: An EMR alert results in increased laboratory test ordering initially for tests drawn on a yearly basis, but the effect on more frequently ordered tests wanes with time if the alert can be silenced by the provider. Nonetheless, it provides a novel mechanism to increase laboratory ordering in patients on high-risk medications that can be adapted for use in other EMR software. Future studies are needed to assess whether physician laboratory test ordering behavior is altered throughout the study period with the use of a non-silencable alert.

Characterization of autoimmune eye disease in association with Down's Syndrome.

Background Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down Syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In 3 consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. Subjects/Methods: This was a multicentered, retrospective case series. De-identified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. Results We characterized 8 subjects (mean age 29 [range, 19-37] years). The mean age of uveitis onset was 23.5 [range, 11-33] years. All 8 subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in 6 and 5 subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. Discussion A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in 3 subjects in our series supports a causal association between DS and autoimmune eye disease.

Long-Term Decrease in Intraocular Pressure in Survivors of Ebola Virus Disease in the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Study.

Objective: Survivors of Ebola virus disease (EVD) experience decreased intraocular pressure (IOP) relative to unaffected close contacts during the first year of convalescence. Whether this effect persists over time and its relationship to intraocular pathology are unclear. We sought to determine whether IOP remained lower in survivors of EVD over 4 years of follow-up and to identify associated risk factors. Design: Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III is a 5-year, longitudinal cohort study of survivors of EVD and their close contacts and is a collaboration between the Liberian Ministry of Health and the United States National Institutes of Health. Participants: Participants who enrolled in PREVAIL III at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 who underwent comprehensive ophthalmic evaluation annually for 5 consecutive visits. Methods: Intraocular pressure was measured at each visit by a handheld rebound tonometer using sterile tips. Comparisons are made between antibody-positive survivors and antibody-negative close contacts. Main Outcome Measures: Intraocular pressure, measured in mmHg, at each study visit. Results: Of 565 antibody-positive survivors and 644 antibody-negative close contacts enrolled in the study at baseline, the majority of participants returned annually, with 383 (67.8%) and 407 (63.2%) participants, respectively, presenting for the final study visit at a median of 60 months after symptom onset. A sustained, relative decrease in IOP was observed in survivors relative to close contacts, with mean difference of -0.72 mmHg (95% confidence interval [CI] -1.18 to -0.27) at the final study visit. This difference remained constant throughout the study period (P = 0.4 for interaction over time). Among survivors, physical examination findings of vitreous cell and OCT findings of vitreous opacities both demonstrated a significant association with decreased IOP at baseline (P < 0.05 for both). After adjusting for such factors, the difference throughout the follow-up (-0.93 mmHg, 95% CI, -1.23 to -0.63) remained significant. Conclusions: Survivors of EVD experienced a sustained decrease in IOP relative to close contacts over a 5-year period after EVD. The results highlight the importance of considering long-term sequelae of emerging infectious diseases within a population. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Adalimumab-associated Acquired Hemophilia in a Patient with Scleritis.

Acquired hemophilia A (AHA) is a rare condition that may be drug-induced. In this case report, we describe a patient who presented with extensive subcutaneous bleeding three years after beginning treatment with adalimumab for necrotizing scleritis. His workup was compatible with drug-induced AHA. He was treated with high-dose corticosteroids, cyclophosphamide, and rituximab. Adalimumab was discontinued. We present this case as an example of a rare, but potentially life-threatening, complication of adalimumab.

Relapsing Thrombotic Thrombocytopenic Purpura (TTP) in a Patient Treated with Infliximab for Chronic Uveitis.

PURPOSE: To report a case of relapsing thrombotic thrombocytopenic purpura (TTP) in a patient treated with infliximab for chronic uveitis. CASE REPORT: A 57-year-old African American woman with chronic anterior and intermediate uveitis, treated with infliximab for more than 1 year, presented with fatigue, dark colored urine, and ecchymosis on her extremities. She was diagnosed with thrombotic thrombocytopenic purpura (TTP) and recovered after treatment. After a remission period of 8 months, she was treated again with infliximab for recurrent intraocular inflammation. She developed a relapse of TTP 4 weeks after reintroducing infliximab. CONCLUSION: Relapsing thrombotic thrombocytopenic purpura can be a rare complication associated with infliximab. To our knowledge, it has not been reported in the literature to date.

Effectiveness of Difluprednate for the Treatment of Anterior Scleritis.

PURPOSE: To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis. DESIGN: Retrospective, interventional case series. METHODS: Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from January 1, 2018, to January 1, 2020, including demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, best-corrected visual acuity (BCVA), and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥2 lines, change in lens status or cataract surgery, and IOP ≥24 mm Hg. RESULTS: Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were White. Forty percent had bilateral disease, and 44% of patients had an associated systemic disease. The majority of eyes (66%) had diffuse anterior scleritis. Eighty-three percent of eyes achieved resolution of scleritis, with a median time of resolution of 6 weeks. Eyes treated with an initial dose of ≥4 times daily were more likely to achieve disease resolution (hazard ratio [HR] = 3.43, 95% confidence interval [CI] 1.19, 9.88, P = .02). Nine eyes had IOP elevation. Four eyes lost ≥2 lines of BCVA, and 1 due to cataract progression. One eye underwent cataract surgery. CONCLUSIONS: Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

Scleritis in Lyme Disease.

PURPOSE: To estimate the incidence of scleritis in Lyme disease and report clinical features. DESIGN: Incidence rate estimate and case series. METHODS: Data were collected from an electronic medical record on patients with scleritis presenting to the Wilmer Eye Institute between January 1, 2012 and December 31, 2020. A diagnosis of Lyme disease was made using the Infectious Diseases Society of America, American Academy of Neurology, and the American College of Rheumatology 2020 joint criteria plus a response to antibiotic therapy. After identifying all new-onset cases of scleritis in the database, the proportion of new-onset scleritis with Lyme disease was calculated. The proportion of Lyme disease cases with scleritis was estimated using the number of cases with Lyme disease from the Baltimore metropolitan area reported to the Centers for Disease Control and Prevention. After querying other major eye centers in the area for any cases of Lyme disease scleritis, none were identified, and the incidence of Lyme disease scleritis was estimated using published U.S. Census data for the greater Baltimore metropolitan area. RESULTS: Six cases of Lyme disease scleritis were identified in the 8-year time frame; 1 additional case was identified in the following year. Lyme disease scleritis accounted for 0.6% of all cases of scleritis, and 0.052% of patients with Lyme disease had scleritis. The estimated incidence of Lyme scleritis was 0.2 per 1,000,000 population per year (95% confidence interval 0-0.4), whereas the estimated incidence of Lyme disease in the area was 3 per 10,000 population per year (95% confidence interval 2.9-3.1). All scleritis cases were anterior, unilateral, without necrosis, and resolved with antibiotic use without relapse in a median of 39.5 days (range 29-57 days). Other features of Lyme disease were present in 4 of 7 patients, including a history of erythema migrans in 2 of 7 patients. CONCLUSIONS: Lyme disease is an uncommon cause of scleritis in endemic areas.

Effectiveness of the Dexamethasone Implant in Lieu of Oral Corticosteroids in Intermediate and Posterior Uveitis Requiring Immunosuppression.

PURPOSE: To evaluate dexamethasone intravitreal implant effectiveness in lieu of high-dose oral prednisone for short-term treatment of noninfectious intermediate and posterior uveitis in patients requiring immunosuppression. METHODS: This is a proof-of-concept, open-label, non-comparative clinical trial with 12-month follow-up. The primary outcome was uveitis control without additional prednisone at 6 and 12 months. Secondary outcomes were need for multiple implants or additional prednisone, and safety data. RESULTS: 20 patients (28 eyes) were enrolled- 16 eyes had control by 6 months; 20 by 12 months. No patients required high-dose prednisone. 6 patients enrolled on prednisone: 2 stopped; 4 tapered to 7.5 mg daily or less by 12 months. 16 eyes required multiple implants; five required cataract surgery; 12 required drops to control IOP; 2 underwent glaucoma surgery. CONCLUSIONS: The dexamethasone implant was effective in lieu of high-dose prednisone although the majority required multiple implants. All patients decreased or discontinued prednisone during follow-up.

Uveitis for the non-ophthalmologist.

The uveitides are a heterogeneous group of diseases characterized by inflammation inside the eye. The uveitides are classified as infectious or non-infectious. The non-infectious uveitides, which are presumed to be immune mediated, can be further divided into those that are associated with a known systemic disease and those that are eye limited,-ie, not associated with a systemic disease. The ophthalmologist identifies the specific uveitic entity by medical history, clinical examination, and ocular imaging, as well as supplemental laboratory testing, if indicated. Treatment of the infectious uveitides is tailored to the particular infectious organism and may include regional and/or systemic medication. First line treatment for non-infectious uveitides is corticosteroids that can be administered topically, as regional injections or surgical implants, or systemically. Systemic immunosuppressive therapy is used in patients with severe disease who cannot tolerate corticosteroids, require chronic corticosteroids at >7.5 mg/day prednisone, or in whom the disease is known to respond better to immunosuppression. Management of many of these diseases is optimized by coordination between the ophthalmologist and rheumatologist or internist.

BUCKLE-ASSOCIATED EPITHELIAL CYST MASQUERADING AS INTRAOCULAR INFLAMMATION.

BACKGROUND/PURPOSE: To describe a case of a rare, late scleral buckle-related complication, which was masquerading as ocular inflammation. METHODS: Case report. RESULTS: A 63-year-old woman with ocular history significant for cataract extraction with intraocular lens placement and retinal detachment repaired through pars plana vitrectomy and scleral buckle presents with anterior chamber inflammation and debris in the left eye. Uveitis workup was negative for any associated systemic disease. Anterior chamber washout and biopsy were nondiagnostic. At postoperative Month 1, she had recurrent anterior chamber debris and new debris noted in the vitreous cavity. A pars plana vitrectomy was performed, and during intraoperative scleral depression, copious strands of whitish material were expressed into the vitreous cavity. The scleral buckle was removed with additional whitish material noted within the encapsulated area. Papanicolaou stain of the material demonstrated a mixture of epithelial cells, histiocytes, lymphocytes, plasma cells, and neutrophils consistent with an epithelial cyst. CONCLUSION: Epithelial inclusion cysts are a rare complication of scleral buckle placement. These cysts are lined by a nonkeratinized, stratified squamous epithelium with or without goblet cells and most commonly occur after ocular trauma, inflammation, or surgical procedures. To the best of our knowledge, this is the first reported case of erosion of an epithelial inclusion cyst into the vitreous cavity.

Escalation to Weekly Adalimumab for the Treatment of Ocular Inflammation.

Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases.Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing.Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months.Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.

Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes.

PURPOSE: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with active CMV retinitis evaluated at a tertiary care academic center. METHODS: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). MAIN OUTCOME MEASURES: The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. RESULTS: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CONCLUSIONS: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.