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Background: Optic disc edema is a feature of many ophthalmic and neurologic conditions. It remains an underappreciated feature of birdshot chorioretinitis (BSCR), leading to delay in diagnosis and treatment. The purpose of our study was to identify clinical features that are concomitant with optic disc edema and suggest a diagnosis of BSCR., Methods: Retrospective multicenter case series of 29 patients who were referred to a neuro-ophthalmologist or uveitis specialist for evaluation of disc edema and were ultimately diagnosed with BSCR., Results: Fifty-four eyes of 30 patients, from the practices of 15 uveitis specialists, met the eligibility criteria. In addition to disc edema, concomitant features in all patients included vitritis, chorioretinal lesions, and retinal vasculitis. Visual recovery to 20/40 or better occurred in 26 of 29 patients. Visual acuity remained 20/100 or worse in 2 patients previously diagnosed with idiopathic intracranial hypertension, 1 patient previously diagnosed with optic neuritis, and 1 patient for whom treatment was delayed for years, leading to optic disc atrophy., Conclusions: Optic disc edema is a presenting feature in some cases of BSCR. A diagnosis of BSCR should be considered when disc edema occurs with vitritis, chorioretinal inflammation, and retinal vasculitis. Patients should be referred to a uveitis specialist for treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Opthalmology Society.)

Purpose: To study the efficacy and safety of suprachoroidal CLS-TA (proprietary suspension of triamcinolone acetonide) in uveitic macular edema (UME) with and without concurrent systemic corticosteroid or steroid-sparing therapy (ST)., Methods: Post hoc analysis of the PEACHTREE phase 3 randomized trial., Results: Among UME patients receiving no ST, at week 24, mean BCVA change was +15.6 letters in 68 CLS-TA patients versus +4.9 letters in 49 sham-control patients ( p < .001), while mean CST change was -169.8 µm versus -10.3 µm, respectively ( p < .001). Among patients receiving ST, at week 24, mean BCVA change was +9.4 letters in 28 CLS-TA patients versus -3.2 letters in 15 sham-control patients ( p = .019), while mean CST change was -108.3 µm versus -43.5 µm, respectively ( p = .190). No SAEs related to treatment were reported., Conclusions: A clinically meaningful benefit of CLS-TA was noted in UME patients, regardless of concurrent ST usage. Abbreviation and Acronyms CST = central subfield thickness; BCVA = best corrected visual acuity; ME = macular edemaI; IVT = intravitreal; AE = adverse event; FA = fluocinolone acetonide; SD-OCT = spectral-domain optical coherence tomography; NIU = noninfectious uveitis; SAE = serious adverse event; TEAE = treatment emergent adverse event; ITT = intent to treat; CI = confidence interval.

Purpose: To assess treatment burden in patients with diabetic macular edema (DME) after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN)., Design: Prospective and retrospective analyses of a 36-month, phase 4, open-label, observational study., Methods: Setting: Multicenter., Patient Population: Included patients had DME and previously received corticosteroid treatment without a clinically significant rise in intraocular pressure (IOP) (N = 202 eyes in 159 patients). Patients were not randomized., Observation Procedures: Prospective, observational treatment burden data were analyzed for their relationship to safety and functional efficacy outcomes across 36 months., Main Outcome Measures: Outcomes included the mean number of yearly treatments, supplemental-free probability over time, best-corrected visual acuity, and monitoring of IOP-related events., Results: Over 36 months, the mean number of yearly treatments decreased from 3.5 before FAc to 1.7 after FAc; at 36 months, 68.3% of patients required 0 to 2 treatments per year. After FAc, the percentage of eyes requiring supplemental therapy decreased vs before FAc (P < .0001 for each). Through 36 months, 25% of FAc-treated eyes did not require supplemental treatment. At 36 months, mean best-corrected visual acuity increased by 4.5 letters vs a decline of 6.4 letters in the 36 months before FAc. IOP elevations >25 mm Hg occurred in 18.2% of eyes that did not receive supplemental treatment after FAc vs 27.2% of eyes that received supplemental treatments, which included additional intraocular steroids., Conclusions: Over 36 months, the FAc implant is associated with improved visual outcomes and better disease control as measured by a significant reduction in yearly treatment burden in patients with DME., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose : To assess efficacy of adalimumab versus placebo in patients with active or inactive noninfectious intermediate, posterior, or panuveitis across different etiologies. Methods : VISUAL I (V-I) and VISUAL II (V-II) clinical trials included adults with active or inactive uveitis, respectively, randomized to receive adalimumab or placebo. In a post hoc subgroup analysis, time to treatment failure (TTF) starting at week 6 (V-I) or week 2 (V-II) was analyzed using the Kaplan-Meier method. Hazard ratios (HR) for TTF with 95% CI were calculated with Cox proportional hazards regression. Results : The analysis included 217 V-I patients and 226 V-II patients. Treatment failure occurred later and risk was significantly lower in patients with idiopathic uveitis receiving adalimumab versus those receiving placebo in V-I (HR = 0.50 [CI, 0.30-0.84]; P = .006) and V-II (HR = 0.43 [CI, 0.22-0.83]; P = .010). Conclusions : Treatment failure risk was lower in patients with idiopathic noninfectious uveitis receiving adalimumab versus those receiving placebo.

Angiostrongylus cantonensis, commonly known as the rat lungworm, is mostly found in Asia, the Pacific Basin, and the Caribbean, but is also endemic in Hawai'i, especially on the Island of Hawai'i. Ocular angiostrongyliasis is an uncommon but previously reported complication associated with permanent vision loss. This is the first reported case of ocular angiostrongyliasis involving the retina or posterior segment of the eye in the US. A 24-year-old male from Chicago visited the Island of Hawai'i, where he worked on a farm and ate a vegetarian diet. When he returned to Chicago, he became sick and was hospitalized for eosinophilic meningitis. One month later, he developed a retinal detachment which required surgical repair involving a pars plana vitrectomy. During the reattachment of the retina during surgery, a live motile was identified nematode in the subretinal space. An endolaser probe immobilized and killed the nematode, and it was subsequently extracted through the sclerotomy. Thermal scars around all retinal holes including the retinotomy site were made to stabilize the retina, and perfluoropropane gas was injected to achieve temporary tamponade. Thereafter, the patient's cerebrospinal fluid returned positive for angiostrongylus cantonensis antibodies. During extended follow-up, the patient eventually lost all vision in the affected eye due to recurrent retinal detachment. This case of ocular angiostrongyliasis demonstrates the importance of obtaining travel history from endemic areas, knowing the risk of developing eosinophilic meningitis, and understanding the risk of permanent vision loss in cases involving the retina., (©Copyright 2021 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Purpose: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis., Design: Open-label, multicenter, phase 3 extension study (VISUAL III)., Participants: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis)., Methods: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose., Main Outcome Measures: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids., Results: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively., Conclusions: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS)., Design: Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies., Participants: Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale)., Methods: Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 μg (n = 208), 440 μg (n = 208), or 880 μg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg dose., Main Outcome Measures: The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events., Results: A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 μg compared with 44 μg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups., Conclusions: Intravitreal sirolimus 440 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Uveitis may represent an opportunity to diagnose spondyloarthropathies (SpA) earlier and influence treatment decisions. We describe the percentage of acute anterior uveitis (AAU) in a diverse group of SpA patients seen at one academic setting and compare demographic and clinical characteristics according to the presence of uveitis. We conducted a retrospective study of patients with SpA and AAU (January 2016-June 2017). Patients were identified using ICD-10 and administrative claim codes, diagnoses were confirmed through chart review. Extracted data included demographics, laboratory, clinical data, treatment and Routine Assessment of Patient Index Data 3 (RAPID3) scores based on Multidimensional Health Assessment Questionnaire (MDHAQ). Baseline description and comparison between the two groups were performed. We included 190 patients, mostly men (59.5%), with a mean age of 45.9 years: 48% with ankylosing spondylitis (AS), 26% with psoriatic arthritis (PsA), 22% with undifferentiated SpA, and 4% with SpA associated with inflammatory bowel disease (IBD). Uveitis was identified in 17% of patients, ranging from 25% in AS to 4% in PsA. Time from symptom onset to SpA diagnosis was longer in patients with uveitis (10.9 versus 5.9 years, p < 0.001). A higher percentage of patients with uveitis were HLA-B27 positive (85% versus 67%, p = 0.02). The prevalence of uveitis in our population was 17%, slightly lower than previously reported in the literature. There was a diagnostic delay of about 7 years, significantly longer in patients with uveitis. New screening strategies in collaboration with ophthalmology may lead to earlier diagnosis and better outcomes.

Background: Standard preoperative education for total knee arthroplasty (TKA) has been shown to have no effect on postoperative outcomes. This may be because such education programs fail to educate patients about pain. Pain neuroscience education (PNE) focuses on teaching people more about pain from a neurobiological and neurophysiological perspective., Design and Setting: Case Series., Aim: To determine the immediate effects, if any, of providing PNE before TKA surgery on patient self-report measures., Participants: Twelve patients (female = 10) prior to TKA for knee osteoarthritis (OA)., Intervention: Preoperative educational session by a physical therapist on the neuroscience of pain, accompanied by an evidence-based booklet., Main Outcome Measures: Comparison of pre- and post-PNE self-report measures on knee pain (NPRS), Pain Catastrophization Scale (PCS), fear of movement (TSK), and beliefs about TKA; as well as three physical performance measures - knee flexion active range of motion, 40 m self-paced walk, and pressure pain threshold (PPT)., Results: Immediately following the PNE, patients had statistically significant lower TSK scores, increased PPT, and improved beliefs about their upcoming surgery. There were no significant changes in knee pain, function, or flexion active range of motion., Conclusions: Results appear to suggest that immediately after PNE, patients scheduled for TKA had statistically significant changes in fear of movement, decreased sensitivity to pain and positive shifts in their beliefs about their future knee surgery. Larger trials with control/comparison groups are warranted to determine the true effects of preoperative PNE for patients about to undergo TKA.

Background/purpose: To describe a case of bilateral macular edema appearing after treatment with rituximab., Methods: This is a case report describing macular edema after rituximab infusions. The information was collected retrospectively through chart review., Results: A 53-year-old patient known for IgG4-related disease of the face and sinuses presented with bilateral decreased visual acuity from cystoid macular edema shortly after undergoing two rituximab infusions. Laboratory workup did not reveal any underlying systemic etiology. Treatment with topical and oral corticosteroids as well as with anti-vascular endothelial growth factor injections led to mild improvement. Treatment with intraocular triamcinolone resulted in complete resolution of the edema, although accompanied by an increase in intraocular pressure., Conclusion: Rituximab has been previously associated with macular edema. Macular edema causing visual loss shortly after receiving rituximab may respond to discontinuation of the rituximab and local steroid injection.

In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 μg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 μg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-μg group than in the 44-μg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 μg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Electronic health record (EHR) systems based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding of disease entities are increasingly being used to generate large data sets for analysis. However, the reproducibility of ICD-10 coding in uveitis has not been assessed across EHR platforms, and imprecision in coding may lead to improper conclusions in big-data analyses., Objective: To compare ICD-10 coding of uveitis using 2 EHR systems., Design, Setting, and Participants: This study compares ICD-10 codes for 27 uveitic diseases generated by the Epic and MDIntelleSys EHR systems to the ICD-10 descriptions associated with the codes. No patient data were assessed in this study., Main Outcomes and Measures: The number of diseases for which ICD-10 coding differed between the 2 systems., Results: Thirteen of 27 uveitic diseases were coded differently by the 2 EHR systems. Coding imprecision was notable in that the Epic system returned 16 ICD-10 codes and the MDIntelleSys returned 12 ICD-10 codes to describe 13 diseases; 4 diseases had multiple codes returned, and 6 codes were used to describe more than 1 disease. For example, MDIntelleSys uses ICD-10 code H30.13 for both birdshot choroiditis and acute retinal necrosis, while Epic uses H30.9 for both birdshot choroiditis and multiple evanescent white dot syndrome; MDIntelleSys uses this code for multifocal choroiditis. Furthermore, the ICD-10 descriptions for certain codes lack specificity, allowing variable interpretation by the coder., Conclusions and Relevance: This study suggests there is substantial disparity in the ICD-10 codes that are generated for specific uveitides by the 2 EHR systems studied. This result implies that analysis of large databases generated from the pooling of EHR data could produce results with substantial bias because of misclassification resulting from conflicting and imprecise coding of uveitides. Therefore, research into outcomes, costs, health care utilization, and epidemiology in uveitis might be improved if a more uniform coding system to describe ocular inflammatory disease is implemented.

Purpose: To describe a case of rickettsial retinitis in a traveler returning from Africa., Method: Case description., Results: A 67-year-old woman returning from an excursion in the jungles of Africa presented with a 2-day history of floaters and decreased vision in the right eye. In the two preceding weeks, she had experienced fever, malaise, a black eschar on the right elbow, and a rash on her extremities. Examination revealed panuveitis with a solitary, white retinal lesion adjacent to a retinal vessel in the posterior pole of each eye. Extensive diagnostic workup revealed a positive serology for rickettsial antibodies. Her treatment consisted of a course of oral doxycycline., Conclusion: Rickettsial retinitis is an emerging ocular infection in several endemic areas. This case description constitutes the first report of spotted fever group rickettsial retinitis in a traveler to Africa.

Purpose: To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis)., Design: Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus., Participants: Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol., Methods: Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120., Main Outcome Measures: The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented., Results: A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated., Conclusions: Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids., Methods: We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838., Findings: Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group)., Interpretation: Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis., Funding: AbbVie., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To report the first documented case of HLA-A29-positive birdshot chorioretinopathy in an African American patient., Methods: A 51-year-old African American woman presented with a 10-year history of photopsia, progressive decrease in visual acuity, metamorphopsia, and new nyctalopia. Both fundi showed evidence of periphlebitis, arterial attenuation, macular edema, and diffuse chorioretinal atrophy., Results: Fluorescein angiography revealed diffuse vascular leakage, and indocyanine green showed evenly distributed and symmetrical hypofluorescent spots, which were difficult to appreciate on fundoscopy. Workup revealed a positive HLA-A29 and was negative for sarcoid, tuberculosis, and syphilis., Conclusion: Birdshot chorioretinopathy overwhelmingly affects non-Hispanic Caucasians, but there have been rare reported cases in other ethnicities including Hispanics and African Americans. This patient's ethnicity may have contributed to the 10-year delay in diagnosis. To our knowledge, this is the first documented HLA-A29 positive case of birdshot chorioretinopathy in an African American. HLA-A29 may be a useful supportive test in cases with classic clinical presentation in non-Caucasian patients to enable the correct diagnose in a timely manner.

The diabetic macular edema (DME) treatment paradigm has evolved as the understanding of the disease pathology has grown. Since 2012, four pharmacotherapies have been approved by the U.S. Food and Drug Administration for the treatment of DME. First-line treatment of DME with anti-vascular endothelial growth factor [VEGF] agents has become the gold standard; however, an appreciable percentage of patients do not respond to anti-VEGF therapies. In patients who inadequately respond to anti-VEGF therapies, the underlying disease pathology may be mediated by a multitude of growth factors and inflammatory cytokines. For these patients, corticosteroids are an attractive treatment option because they not only downregulate VEGF, but also an array of cytokines. The phase 3 MEAD and FAME trials demonstrated significant visual acuity improvements associated with dexamethasone and fluocinolone acetonide, respectively, in patients with DME; however, class-specific adverse events, including increased intraocular pressure and cataract development, must be considered before use. A panel of experts gathered during the 2015 annual meeting of the American Academy of Ophthalmology for a roundtable discussion focused on patient selection and adverse event management associated with the use of the 0.19 mg fluocinolone acetonide intravitreal implant., (Copyright 2016, SLACK Incorporated.)

Purpose: The purpose of this was to describe the clinical improvement of chronic central serous chorioretinopathy in a patient treated with rifampin for tuberculosis., Methods: A 54-year-old Hispanic man with a distant history of pulmonary tuberculosis presented with reduced vision in the right greater than left eye for over 1 year. He had diffuse chorioretinopathy in both eyes and a serous retinal detachment in his right eye. The findings were most consistent with chronic central serous chorioretinopathy, although tuberculosis -related choroiditis could not be excluded. Treatment with multidrug antituberculosis medications, including rifampin, resulted in the reduction in leakage and resolution of subretinal fluid. Fluid recurred on cessation of all medications and resolved again with retreatment. Monotherapy with rifampin maintained the absence of fluid., Discussion: This case represents the first report of chronic central serous chorioretinopathy responding to systemic therapy with rifampin. We hypothesize that the clinical response observed is secondary to induction of cytochrome P450 with increased hepatic metabolism of endogenous corticosteroids and a reduction in systemic cortisol levels.

Purpose: To assess the prevalence of hypotony in patients with severe forms of uveitis., Methods: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified., Results: Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01)., Conclusions: Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment.

Purpose: To report a case of cytomegalovirus acute retinal necrosis after a sub-Tenon injection of triamcinolone acetonide in an immunocompetent patient., Methods: A 77-year-old man received a sub-Tenon injection of triamcinolone acetonide for treatment of iritis unresponsive to topical steroids. He subsequently developed unilateral acute retinal necrosis., Results: Vitreous biopsy with polymerase chain reaction analysis was positive for cytomegalovirus. Implantation of a sustained-release ganciclovir device resulted in disease stabilization., Conclusion: Cytomegalovirus can be a causative agent of both anterior uveitis and acute retinal necrosis. A potential complication of a sub-Tenon steroid injection may be viral reactivation causing acute retinal necrosis secondary to localized immunosuppression.

Purpose: To describe the clinical features of central serous chorioretinopathy (CSC) in women and identify factors predictive of complete recovery, moderate visual loss, and prolonged duration., Design: Retrospective observational case series., Participants: Eighty-four eyes in 78 women with CSC seen in our practices between 1982 and 1999., Methods: Univariate and multivariate statistical analysis., Main Outcome Measures: Analyses of three outcome parameters: complete recovery (recovery of visual acuity and complete symptom resolution), moderate visual acuity loss (final acuity less than 20/40), and duration of symptoms greater than 5 months., Results: Sixty-two percent (52 of 84) achieved complete recovery over a median of 5 months (range, 2-108 months) and 88% (74 of 84) had a final vision of 20/40 or better. Patients with subretinal precipitates (P = 0.001), single occurrence (P = 0.002), absence of hormone replacement therapy (HRT) (P = 0.01), duration less than 5 months (P = 0.02), or absence of a pigment epithelial detachment (PED) (P = 0.05) were more likely to recover completely. Recurrence (P = 0.03) and lack of subretinal precipitates (P = 0.03) were associated with a final vision less than 20/40. Age older than 50 (P = 0.004) and the presence of a PED (P = 0.02) were associated with duration longer than 5 months., Conclusions: In women, CSC associated with subretinal precipitates, shorter duration, single occurrence, lack of HRT use, and absence of PED is more likely to resolve completely. CSC occurring in women older than 50 or associated with PED formation is more likely to take longer to resolve.

Purpose: To report our experience with perfluoro-N-octane (PFO) in the surgical management of complicated retinal detachments due to proliferative diabetic retinopathy., Methods: Retrospective review of 18 consecutive eyes of 18 patients with tractional or combined tractional and rhegmatogenous retinal detachments due to severe proliferative diabetic retinopathy managed by pars plana vitrectomy and the intraoperative use of PFO. Preoperative characteristics, intraoperative findings and procedures and postoperative results were recorded., Results: The mean preoperative acuity was 2/200 (range, 20/25 to light perception). The mean final visual acuity was 4/200 (range, 20/20 to no light perception). With a mean follow-up of 6 months, there was an 89% anatomic reattachment rate at the last visit and visual acuity was stable or improved in 72% of eyes., Conclusions: In our experience, PFO is a helpful surgical adjunct in the anatomic reattachment of tractional or combined tractional and rhegmatogenous diabetic retinal detachments. Visual acuity was stabilized or improved in the majority of eyes.

Objective: To assess the results of surgical excision of subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD)., Design: Retrospective, interventional, noncomparative case series., Participants and Intervention: Sixty-four consecutive patients undergoing surgical removal of AMD-related subfoveal CNV were studied. The surgical method included a small retinotomy, subretinal tissue plasminogen activator (t-PA), perfluoro-n-octane, and air-fluid exchange., Main Outcome Measures: Final visual acuity was the main outcome measure; surgical complications and recurrence rates were also assessed., Results: Preoperative visual acuity ranged from 20/100 to 1/200, with a mean of 20/400. Average follow-up was 19 months. The best acuity achieved after surgery ranged from 20/20 to hand motions, with a mean of 20/200. Final visual acuity ranged from 20/50 to light perception, with a mean of 20/400. Final acuity was improved 3 or more lines in 19 eyes (30%) (median, 5 lines), stable in 27 eyes (42%), and 3 or more lines worse in 18 eyes (28%) (median, 4 lines). Factors associated with greater visual improvement included poorer initial acuity, larger CNV size, and smaller subretinal hemorrhage. Analysis of groups similar to Macular Photocoagulation Study subgroups A through D showed an average improvement of 1 line for group C (visual acuity, 20/200 or worse; CNV larger than 2 disc areas). Other preoperative, intraoperative, and postoperative factors, including recurrence and retinal detachment, did not have a significant effect on final visual outcome., Conclusions: After surgical excision of AMD-related subfoveal CNV, vision improved or stabilized in the majority of patients. Surgery may be of greatest value for patients with poorer vision, larger subfoveal CNV, and minimal hemorrhage. Further evaluation of this technique should be accomplished via completion of a controlled, randomized multicenter study.

Purpose: Previous epidemiologic studies of uveitis have focused on predominantly Caucasian populations, and none have been based in the Southeast. We analyzed the epidemiology of uveitis among a referral population with a high percentage of African Americans in the United States., Methods: We evaluated demographic data from 385 consecutive patients referred to the Duke Uveitis Clinic., Results: Of the 385 patients, 120 (31%) were African American and 258 (67%) Caucasian; 237 (62%) were female and 148 (38%) male. The most common diagnoses among the 385 patients were idiopathic panuveitis (64 patients [17%]), idiopathic anterior uveitis (47 patients [12%]), pars planitis (46 patients [12%]), sarcoidosis (44 patients [11%]), and toxoplasmosis (39 patients [10%]). These diagnoses were also the most common among the 120 African American patients: 33 patients (28%) had idiopathic panuveitis, 30 (25%) had sarcoidosis, 10 (8%) had idiopathic anterior uveitis, 8 (7%) had toxoplasmosis, and 6 (5%) had pars planitis. Among the 258 Caucasian patients, the most common diagnoses were pars planitis (39 patients [15%]), idiopathic anterior uveitis (37 patients [14%]), toxoplasmosis (30 patients [12%]), idiopathic panuveitis (28 patients [11%]), and multifocal choroiditis and panuveitis (MCP) (17 patients [7%]). Categorizing diagnoses of all 385 patients by anatomic location, panuveitis was most frequent (148 patients [38%]), followed by anterior uveitis (97 patients [25%]), posterior uveitis (93 patients [24%]), and intermediate uveitis (47 patients [12%])., Conclusions: The higher frequency of sarcoidosis and idiopathic panuveitis than previously reported is related to our larger African American population base. The racial composition of the Southeast does not, however, account for differences such as our higher percentage of MCP; it is possible that other genetic or environmental factors play a role in this region.

Background and Objective: Subfoveal neovascular membranes are usually located either in the subsensory retinal space or below the retinal pigment epithelium (RPE). This article describes the clinical and histopathologic features of subfoveal membranes with both subretinal and sub-RPE components (combined membranes)., Patients and Methods: Six surgically excised subfoveal neovascular membranes from six patients were examined histopathologically. Preoperative and postoperative clinical information was obtained from each patient., Results: Clinically, the combined membranes had no special characteristic features. The most common fluorescein angiographic finding postoperatively was a window defect of the RPE. Visual acuity improved in three patients and became worse in the other three patients., Conclusions: All patients with combined subfoveal neovascular membranes had age-related macular degeneration. In this disease, a single subfoveal membrane may extend into both the subretinal and the sub-RPE spaces. Patients may benefit from surgical removal of the membrane.

Patients with germinal retinoblastoma (those with bilateral disease or positive family history) have a mutation which puts them at risk for developing new tumors. It is unclear whether the frequency of new tumor development is effected by the type of treatment employed. It may be hypothesized that external beam radiation "sterilizes' the whole retina, and thus decreases the risk of new and recurrent tumors. We reviewed our experience with 66 eyes in 47 patients over the past ten years. We did not find a significant difference in the incidence of new and recurrent retinoblastoma among eyes treated with external beam radiation versus focal modalities.

We studied ocular motor performance in 47 subjects with human immunodeficiency virus (HIV) infection and 25 normal control subjects. Saccade accuracy was the most sensitive measure, being significantly poorer for all four HIV-positive groups (asymptomatic, acquired immunodeficiency syndrome [AIDS] without dementia, and AIDS with dementia, and AIDS-related complex) than for control subjects. While saccade duration and peak velocity were not significantly different across groups, the scatter of saccade duration was increased in all HIV-positive groups. Saccade latency was not significantly affected. In both simple and complex antisaccade tasks, the asymptomatic, AIDS, and AIDS dementia groups made significantly fewer correct-way antisaccades than did control subjects. Latencies of correct-way antisaccades were increased for AIDS and AIDS dementia groups in the simple antisaccade trials, and for all HIV-positive groups in the complex trials. Fixation stability was significantly worse in the AIDS dementia group than in control subjects. Smooth pursuit gain was decreased in the asymptomatic, AIDS, and AIDS dementia groups for the least demanding trial. One or more ocular motor abnormalities were present in 15 (88%) asymptomatic subjects, 11 (69%) with AIDS-related complex, and 14 (100%) AIDS patients without or with dementia.

To identify early requirements for zygotic gene activity in Drosophila, we used compound autosomes and autosome-Y translocations to generate embryos deficient for cytologically defined portions of the genome. No obvious gross morphological defects were observed in any deficiency class until the beginning of cycle 14. Only seven autosomal regions were identified with discrete effects visible prior to the onset of gastrulation. These regions include genes with locus-specific effects on the clearing of the cortical cytoplasm during early cycle 14, (22AB), the initiation of the slow and fast phases of cellularization (26BF and 40AC, respectively), the apical-basal distribution of nuclei during cycle 14 (71C-75C) and the closing off of furrow canals during cellularization (100AC). The distal tip of the third chromosome also contains two loci (99DF and 100AC) whose deletion causes multiple nuclei to be cellularized into single cells, a phenotype similar to that produced in embryos totally lacking the X-chromosome.

Partial monosomy of the short arm of chromosome 1 is the most consistent cytogenetic abnormality found in human neuroblastomas, but its overall frequency and significance are unclear. Using a panel of chromosome-1-specific DNA probes that identify restriction fragment length polymorphisms, we demonstrate that 13 of 47 human neuroblastomas (28%) have somatic loss of heterozygosity (LOH) at one or more loci on the distal short arm of chromosome 1. the chromosomal region that shows LOH most consistently is between 1p36.1 and 1p36.3; loss of a gene or genes in this region may be critical for the development or progression of neuroblastomas. The region of LOH in human neuroblastoma may resemble that described for pheochromocytoma, medullary thyroid carcinoma, and melanoma, which are also tumors of neural-crest origin. Although LOH for distal chromosome 1p can occur in early stages of neuroblastoma, the loss usually occurs in tumors of advanced clinical stages. LOH for the short arm of chromosome 1 correlates significantly with N-myc amplification, suggesting that these two genetic events are related. Indeed, these two lesions appear to characterize a genetically distinct subset of particularly aggressive neuroblastomas.