Purpose
To analyze mitochondrial DNA (mt DNA) gene mutations in a 19-year-old female patient, who presented with chronic progressive external ophthalmoplegia (CPEO), together with her mother and younger sister.
Methods
The diagnosis of mitochondrial myopathy was made based on clinical and biologic analysis. Histochemical methods were used to detect ragged-red fibers (RRFs) and ragged-blue fibers (RBFs) on a muscle biopsy of the patient. All mitochondrial gene DNA fragments of the patient, her mother, and younger sister were amplified by polymerase chain reaction. The products were sequenced and compared with reference databases.
Results
A novel T1658C mutation and a known A10006G mutation were identified in the mitochondrial tRNAVal gene and the tRNAGly gene, respectively, in the patient, her mother, and younger sister. The T1658C mutation changes the T loop structure of mitochondrial tRNAVal and the A10006G mutation disturbs the D loop of mitochondrial tRNAGly.
Conclusions
The T1658C and A10006G mutations of mtDNA may be responsible for the pathogenesis of the patient with CPEO.
Objective: To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods: Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results: There is level I evidence from < 5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions: Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Objective: The Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q) is a novel measure of vision-related quality of life (QOL) and function in children. We aim to determine the validity of EYE-Q in childhood uveitis.
Methods: We abstracted medical record data on arthritis and uveitis in a convenience sample of children with juvenile idiopathic arthritis (JIA) and/or uveitis. In addition to the EYE-Q, parents and patients completed questionnaires on overall QOL (Pediatric QOL Inventory - PedsQL), and physical functioning (Childhood Health Assessment Questionnaire - CHAQ).
Results: Among 57 children (8 JIA, 24 JIA and uveitis, 25 uveitis alone), 102 ocular examinations were performed within 1 month of completing questionnaires. Uveitis patients had bilateral disease (69%), anterior involvement (78%), synechiae (51%) and cataracts (49%). Children with vision loss in their better eye (visual acuity (VA) 20/50 or worse) had worse EYE-Q (p = 0.006), and PedsQL (p = 0.028), but not CHAQ scores. The EYE-Q moderately correlated with logMAR VA (rs = −0.43), PedsQL (rs = 0.43) and CHAQ (rs = −0.45), but was not correlated with anterior chamber cells or intraocular pressure. The PedsQL and CHAQ did not correlate with VA or cells. There were strong correlations between the parent and child EYE-Q (rs = 0.62). Cronbach's α for the child report was 0.91. The EYE-Q had strong test-retest reliability (rs=0.75).
Conclusion: The EYE-Q may be an important tool in the assessment of visual outcomes in childhood uveitis and an improvement over general measures in detecting changes in vision-related function.
Aerobic exercise is a common intervention for rehabilitation of motor, and more recently, cognitive function (Intlekofer and Cotman, 2013; Wood et al., 2012). While the underlying mechanisms are complex, BDNF may mediate much of the beneficial effects of exercise to these neurons (Ploughman et al., 2007; Griffin et al., 2011; Real et al., 2013). We studied the effects of aerobic exercise on retinal neurons undergoing degeneration. We exercised wild-type BALB/c mice on a treadmill (10 m/min for 1 h) for 5 d/week or placed control mice on static treadmills. After 2 weeks of exercise, mice were exposed to either toxic bright light (10,000 lux) for 4 h to induce photoreceptor degeneration or maintenance dim light (25 lux). Bright light caused 75% loss of both retinal function and photoreceptor numbers. However, exercised mice exposed to bright light had 2 times greater retinal function and photoreceptor nuclei than inactive mice exposed to bright light. In addition, exercise increased retinal BDNF protein levels by 20% compared with inactive mice. Systemic injections of a BDNF tropomyosin-receptor-kinase (TrkB) receptor antagonist reduced retinal function and photoreceptor nuclei counts in exercised mice to inactive levels, effectively blocking the protective effects seen with aerobic exercise. The data suggest that aerobic exercise is neuroprotective for retinal degeneration and that this effect is mediated by BDNF signaling.
Purpose
To evaluate the utility of low luminance stimuli to functionally probe inner retinal rod pathways in the context of diabetes mellitus in both rat and human subjects.
Methods
Inner retinal dysfunction was assessed using oscillatory potential (OP) delays in diabetic rats. Scotopic electroretinograms (ERGs) in response to a series of increasing flash luminances were recorded from streptozotocin (STZ)-treated and control Sprague-Dawley rats after 7, 14, 20, and 29 weeks of hyperglycemia. We then evaluated OP delays in human diabetic subjects with (DR) and without (DM) diabetic retinopathy using the International Society for Clinical Electrophysiology in Vision (ISCEV) standard scotopic protocol and two additional dim test flashes.
Results
Beginning 7 weeks after STZ, OP implicit times in diabetic rats were progressively delayed in response to dim, but not bright stimuli. In many diabetic subjects the standard ISCEV dim flash failed to illicit measureable OPs. However, OPs became measurable using a brighter, nonstandard dim flash (Test Flash 1, −1.43 log cd s/m2), and exhibited prolonged implicit times in the DM group compared with control subjects (CTRL).
Conclusions
Delays in scotopic OP implicit times are an early response to hyperglycemia in diabetic rats. A similar, inner retinal, rod-driven response was detected in diabetic human subjects without diabetic retinopathy, only when a nonstandard ISCEV flash intensity was employed during ERG testing.
Translational Relevance
The addition of a dim stimulus to standard ISCEV flashes with assessment of OP latency during ERG testing may provide a detection method for early retinal dysfunction in diabetic patients.
Background: Candidal retinitis is a rare but potentially devastating infection in the postoperative patient. Due to the possibility of blindness if the diagnosis and treatment are delayed, we present this report to help educate gynecologic surgeons. Case: A postmenopausal patient presented for the treatment of ovarian carcinoma. Her surgical therapy required radical tumor debulking with partial bowel resection. The patient was begun on intravenous (IV) hyperalimentation through a central venous catheter. On the 7th postoperative day, a cephalosporin antibiotic was administered. Because of persistent fever, a septic workup was instituted and revealed an infected central venous catheter that was culture positive for Candida albicans. The patient complained of visual disturbances and an ophthalmological examination revealed candidal retinitis. Amphotericin B and fluconazole were administered with resolution of her fever and visual changes. Conclusion: The risk factors of malignancy, abdominopelvic surgery, antibiotic therapy, and IV catheters are discussed. In view of the common association of these iatrogenic factors in gynecologic and obstetrical practice, we present this case to help make physicians aware of this potentially devastating infection.
Background: There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. Methods: This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. Results: Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients. Conclusion: Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.
We are interested in developing quantitative tools to study RPE morphology. We want to detect changes in the RPE by strain, disease, genotype, and age. Ultimately these tools should be useful in predicting retinal disease progression. The morphometric data will also help us to understand RPE sheet formation and barrier functions. A clear disruption of the regular cell size and shape appeared in mouse mutants. Aspect ratio and cell area together gave rise to principal components that predicted age and genotype accurately and well before visually obvious damage could be seen.
by
Abdourahman Cham;
Mayank Bansal;
Himanshu K Banda;
Young Kwon;
Paul S Tlucek;
Alexander G Bassuk;
Stephen H Tsang;
Warren M Sobol;
James C Folk;
Steven Yeh;
Vinit B Mahajan
OBJECTIVE: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. PATIENTS AND METHODS: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT) were also analyzed. RESULTS: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA) implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5) required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser peripheral iridotomy. Patient 4 had both hypotony and elevated IOP that required periodic antiglaucoma medication in the FA-implanted eye. Patient 3 did not develop steroid-response glaucoma in either eye. Optic disk examinations were obscured by fibrosis and better assessed with OCT. CONCLUSION: ADNIV patients show combined mechanism secondary glaucoma best assessed by OCT of the optic disk. The FA implants have reduced uveitic and neovascular glaucoma. Nevertheless, IOP management remains complex due to steroid-response glaucoma, angle closure glaucoma, and hypotony.
Objective
To describe the clinical features and imaging characteristics in unilateral acute idiopathic maculopathy (UAIM).
Methods
This is a retrospective review of four patients diagnosed with UAIM. Clinical characteristics (age, symptoms, Snellen visual acuity (VA), and funduscopic features) and images from spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein (FA), and indocyanine green (ICG) angiography were analyzed.
Results
The median age at presentation was 31 years (range 27–52 years). The median interval between symptom onset and presentation was four weeks (range 1–20 weeks). Associated systemic findings included a viral prodrome (50%), orchitis (50%), hand-foot-mouth disease (25%), and positive Coxsackie virus titers (50%). The median presenting VA was 20/400 (range 20/70–1/400), which improved to 20/30 (range 20/20–20/60) at final follow-up. The median follow-up time was 6 weeks (range 0–8 weeks). Early in the disease course, the central macula developed irregular, circular areas of white-grey discoloration. Following recovery, the macula had a stippled retinal pigment epithelium characterized by rarefaction and hyperplasia. FA demonstrated irregular early hyperfluorescence and late subretinal hyperfluorescence. SD-OCT showed a partially reversible disruption of the outer photoreceptor layer. FAF initially revealed stippled autofluorescence that eventually became more hypoautofluorescent. ICG showed “moth-eaten” appearing choroidal vasculature, suggestive of choroidal inflammation.
Conclusions
The imaging characteristics highlight the structural changes during the active and resolution phases of UAIM. The visual recovery correlates with structural changes and suggests that the pathogenesis involves inflammation of the inner choroid, retinal pigment epithelium, and outer photoreceptor complex that is partially reversible.