Ocular flutter is a rare ophthalmic finding that could represent paraneoplastic phenomena. In adults it is most commonly associated with small cell lung cancer (SCLC). Most patients also present with other neurological defects. We report the case of a 75-year-old woman who presented with isolated ocular flutter. The ensuing workup was significant for an early lung adenocarcinoma that would not have been biopsied otherwise due to its small size. To our knowledge, this is the first reported case of isolated ocular flutter as the presenting symptom of non-SCLC.
OBJECTIVE: To establish the safety and efficacy of infliximab for the treatment of refractory noninfectious uveitis. DESIGN: Retrospective, interventional, noncomparative cohort study. PARTICIPANTS: Eighty-eight patients from a single-center private practice. METHODS: Patients with chronic, recalcitrant uveitis treated with infliximab (Remicade; Janssen Biotech, Inc., Titusville, NJ) were identified through an electronic medical record database. All charts were reviewed for sex, diagnosis, location of inflammation, presence of vasculitis, prior immunomodulatory treatments, duration of infliximab treatment, dose received, secondary side effects, and other medications continued while receiving treatment with infliximab. MAIN OUTCOME MEASURES: The primary outcome measures were the rate of remission, time to remission, relapse rate, failure rate, and patient tolerance. Additional analysis aimed to identity risk factors that would predict a higher success rate of infliximab to treat various types of noninfectious uveitis. RESULTS: Of the 72 patients (81.8%) who achieved clinical remission while being treated with infliximab, 42 (58.3%) required additional immunomodulatory medications. At 7, 18.1, and 44.7 weeks, 25%, 50%, and 75% of patients, respectively, achieved clinical remission off all corticosteroids. Thirty-two patients (36.4%) experienced at least 1 side effect while on infliximab therapy, and 17 patients (19.3%) discontinued treatment secondary to 1 or more intolerable side effects. The most common adverse effects were skin rash (9.1%) and fatigue (8%). Factors associated with a higher chance to achieve clinical remission were nonidiopathic uveitis (P < 0.001), intermediate or panuveitis (P < 0.001), absence of vasculitis (P < 0.001), and a starting dose ≥5 mg/kg (P < 0.011). CONCLUSIONS: Infliximab induces a high rate of complete clinical remission in recalcitrant uveitis and is well tolerated by most patients.
Pediatric uveitis is a topic of special interest not only because of the unique diagnostic and therapeutic challenges but also because of the lifetime burden of vision loss if the problem is not adequately treated, as well as the economic and psychological toll on the family. Often, uveitis in children is discovered as part of a routine eye exam; this silent, insidious inflammation can be difficult to treat and can lead to further complications if not handled skillfully. Corticosteroids have long been the mainstay of therapy; however, the significant associated side effects mandate a corticosteroid-sparing therapeutic regimen in pursuit of remission. In this review, we cover the therapeutic options for pediatric uveitis, specifically focusing on the most common non-infectious varieties, juvenile idiopathic arthritis-associated uveitis and pars planitis.
PURPOSE: Exfoliation syndrome (ES) is commonly associated with glaucoma, premature cataracts, and other ocular and systemic pathologies. LOXL1 gene variants are significantly associated with ES; however, the role of the protein in ES development remains unclear. The purpose of this study was to characterize the ocular phenotype in Loxl1(-/-) (null) mice. METHODS: Loxl1 null mice and strain-matched controls (C57BL) were evaluated by clinical and histologic analyses. RESULTS: Anterior segment histology showed a pronounced vesiculation of the anterior lens in the null mice. The lesions were subcapsular and in direct apposition with the posterior iris surface. Fluorescein angiography showed increased diffusion of fluorescein into the anterior chamber of the null mice compared with age-matched controls (P = 0.003, two-tailed, unequal variance t-test), suggesting compromise of the blood-aqueous barrier. Intraocular pressure measurements were within the normal range (16.5 ± 2.0 mm Hg) in null mice up to 1 year of age. Immunohistochemistry showed decreased elastin in the iris and ciliary body in the null mouse compared with controls. CONCLUSIONS: Elimination of LOXL1 in mice impairs the blood-aqueous humor barrier in the ocular anterior segment and causes lens abnormalities consistent with cataract formation, but does not result in deposition of macromolecular material or glaucoma. These results show that mice lacking LOXL1 have some ES features but that complete disease manifestation requires other factors that could be genetic and/or environmental.
PURPOSE: To describe a favorable outcome after the surgical repair of a very large macular hole with a neurosensory operculum. METHODS: Case report. A 42-year-old man with a history of decreased vision for 3 months was found to have vision of 20/400, a very large macular hole (1159 μm in diameter), and an operculum suspended on the posterior hyaloid above the hole. RESULTS: Vitrectomy and internal limiting membrane peel were performed. The operculum was processed for histology and found to contain neurons and glial cells. Fourteen months later, the patient's vision improved to 20/60. CONCLUSION: Very large macular holes have traditionally been considered to have a poor prognosis. Here, we demonstrate that such large holes can be repaired with good visual outcome, even in the setting of an operculum consisting of avulsed neural retina.
Age-related macular degeneration (AMD) is a complex disease resulting from the interplay of genetic predisposition and environmental exposures, and has been linked to oxidative stress and inflammatory mechanisms. Lead and cadmium can accumulate in human retinal tissues and may damage the retina through oxidative stress, and may thereby play a role in the development of AMD. We examined associations between blood lead, blood cadmium, and urinary cadmium concentrations and the presence of AMD in 5390 participants aged 40 years and older with blood lead and blood cadmium measures and a subsample of 1548 with urinary cadmium measures in the 2005-2008 National Health and Nutrition Examination Surveys. AMD was identified by grading retinal photographs with a modification of the Wisconsin Age-Related Maculopathy Grading System. The weighted prevalence of AMD was 6.6% (n=426). Controlling for age, gender, race/ethnicity, education and body mass index, adults in the highest blood cadmium quartile had higher odds of AMD compared to the lowest quartile (odds ratio [OR], 1.56; 95% CI, 1.02-2.40), with a significant trend across quartiles (p-trend=0.02). After further adjustment for pack-years of cigarette smoking, estimates were somewhat attenuated (OR, 1.43; 95% CI, 0.91-2.27; p-trend=0.08). Similar associations were found with urinary cadmium. The association between urinary cadmium and AMD was stronger in non-Hispanic whites (NHW) than in non-Hispanic blacks (NHB) (OR, 3.31; 95% CI, 1.37-8.01 for levels above versus below the median among NHW; OR,1.45; 95% CI, 0.40-5.32 for levels above versus below the median among NHB; p-interaction=0.03). We found no association between blood lead levels and AMD. Higher cadmium body burden may increase risk of AMD, particularly among non-Hispanic white individuals; however, additional studies are needed before firm conclusions can be drawn.
IMPORTANCE: Research has indicated some shared pathogenic mechanisms between age-related macular degeneration (AMD) and cardiovascular disease (CVD). However, results from prior epidemiologic studies have been inconsistent as to whether AMD is predictive of future CVD risk. OBJECTIVE: To systematically review population-based cohort studies of the association between AMD and risk of total CVD and CVD subtypes, coronary heart disease (CHD) and stroke. DATA SOURCES: A systematic search of the PubMed and EMBASE databases and reference lists of key retrieved articles up to December 20, 2012 without language restriction. DATA EXTRACTION: Two reviewers independently extracted data on baseline AMD status, risk estimates of CVD and methods used to assess AMD and CVD. We pooled relative risks using random or fixed effects models as appropriate. RESULTS: Thirteen cohort studies (8 prospective and 5 retrospective studies) with a total of 1,593,390 participants with 155,500 CVD events (92,039 stroke and 62,737 CHD) were included in this meta-analysis. Among all studies, early AMD was associated with a 15% (95% CI, 1.08-1.22) increased risk of total CVD. The relative risk was similar but not significant for late AMD (RR, 1.17; 95% CI, 0.98-1.40). In analyses restricted to the subset of prospective studies, the risk associated with early AMD did not appreciably change; however, there was a marked 66% (95% CI, 1.31-2.10) increased risk of CVD among those with late AMD. CONCLUSION: Whereas the results from all cohort studies suggest that both early and late AMD are predictive of a small increase in risk of future CVD, subgroup analyses limited to prospective studies demonstrate a markedly increased risk of CVD among people with late AMD. Retrospective studies using healthcare databases may have inherent methodological limitations that obscure such association. Additional prospective studies are needed to further elucidate the associations between AMD and specific CVD outcomes.
Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. We report that depletion of the NuRD complex by in vivo RNAi and conditional knockout of the core NuRD subunit Chd4 profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses in the rodent cerebellar cortex in vivo. By interfacing genome-wide sequencing of transcripts and ChIP-seq analyses, we uncover a network of repressed genes and distinct histone modifications at target gene promoters that are developmentally regulated by the NuRD complex in the cerebellum in vivo. Finally, in a targeted in vivo RNAi screen of NuRD target genes, we identify a program of NuRD-repressed genes that operate as critical regulators of presynaptic differentiation in the cerebellar cortex. Our findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that drives synaptic connectivity in the mammalian brain.
PURPOSE: To determine the safety and efficacy of autologous postauricular dermal grafts as posterior lamellar spacing material in patients with lower eyelid retraction. METHODS: At a tertiary care institution, 10 eyelids of 10 patients (7 men, 3 women; mean 56 years, range 24-78) who underwent repair of lower eyelid retraction using a postauricular dermal graft between July 2008 and December 2010 were retrospectively assessed. Data collected included patient demographics, etiology of retraction, and surgical history. Outcome measures included preoperative and postoperative eyelid position and surgery-related complications. RESULTS: Postoperative results were favorable: mean preoperative inferior scleral show was 3.3 ± 2.6 mm compared with 0.3 ± 1.2 mm postoperatively, p = 0.004 (paired t test). Mean follow up was 39.2 weeks (range 12-94). Complications included keratinization of the graft with vellus hair growth (n = 1) and ectropion (n = 1), both corrected with minor surgical interventions. One patient achieved overcorrection but declined further treatment. No donor site complications were encountered. CONCLUSIONS: These data suggest postauricular dermal grafts are effective posterior lamellar spacers in the correction of eyelid retraction. They have adequate rigidity whilst maintaining sufficient pliability to mold to the globe. Resorption, common to acellular dermis matrix allografts and xenografts, was not encountered. Donor site complications were not encountered. Complications shared with other material include overcorrection and ectropion. Complications unique to autologous dermis include keratinization and hair growth.
