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Glycemic and Blood Pressure Control in an Asian Malay Population With Diabetes and Diabetic Retinopathy [Epidemiology] :
Objective To examine the prevalence of and factors associated with suboptimal glycemic and blood pressure (BP) control in a Malay population with diabetes mellitus in Singapore.Methods The Singapore Malay Eye Study was a population-based survey of 3280 Malay individuals (78.7% response rate) aged 40 to 80 years. Diabetes was defined as a nonfasting glucose level of 200 mg/dL or greater, use of diabetic medication, or physician diagnosis. Diabetic retinopathy (DR) was graded from retinal photographs using the modified Airlie House classification. Optimal control was defined as a hemoglobin A_1c level of less than 7% and BP of 130/80 mm Hg or lower.Results In participants with diabetes (n = 768), only 26.9% had optimal glycemic and 13.4% optimal BP control, respectively. In those with DR (n = 272), rates of optimal glycemic and BP control were even lower (17.4% and 10.3%, respectively). After adjusting for age, sex, socioeconomic status, and other factors, compared with participants with optimal glycemic control, those with suboptimal control were younger (P = .005), more likely to be unaware of their diabetes status (P < .001), and taking medication for diabetes (P < .001) and had higher levels of total cholesterol (P = .009) and DR (P < .001). After adjusting for similar risk factors, compared with participants with optimal BP control, those with suboptimal BP control were older (P = .006) and more likely to have higher total cholesterol levels (P = .002), BMIs (P = .04), and DR (P = .02).Conclusions In this Asian Malay population with diabetes, more than three-quarters had poor glycemic and BP control. Strategies to improve awareness and implement evidence-based guidelines are needed to reduce the effect and burden of diabetic complications in Asia.Published online July 12, 2010 (doi:10.1001/archophthalmol.2010.168).
Selected Sun-Sensitizing Medications and Incident Cataract [Clinical Sciences] :
Objective To examine the relationship between the use of sun-sensitizing medications and cumulative incidence of age-related cataract.Methods Sun exposure was estimated from residential history of adults in the Midwestern community of Beaver Dam, Wisconsin, which permitted calculation of Wisconsin sun-years at the baseline examination. Medication history was reported at each examination. Cataract presence was determined by standardized lens photographs that were taken at each examination and graded according to standard protocols.Results No significant effects were noted of Wisconsin sun-year exposure or use of sun-sensitizing medications on the cumulative incidence of any type of age-related cataract when controlling for age and sex. However, an interaction term combining Wisconsin sun-years and use of any sun-sensitizing medication was significant (P = .04) such that risk of cortical cataract is significantly higher for the joint risk group. Further controlling for the presence of diabetes mellitus, history of heavy drinking, and hat or sunglasses use did not alter the relationships.Conclusions Data suggest that the use of sun-sensitizing medications interacts with sun exposure to influence the risk of cortical cataract, a common age-related cataract. If confirmed, this finding may have important implications for medication use.Published online June 14, 2010 (doi:10.1001/archophthalmol.2010.138).
About This Journal [About This Journal]
A Randomized Clinical Trial Comparing Contact Lens With Intraocular Lens Correction of Monocular Aphakia During Infancy: Grating Acuity and Adverse Events at Age 1 Year [Clinical Trial] :
Objective To compare the visual outcomes and adverse events of contact lens with primary intraocular lens (IOL) correction of monocular aphakia during infancy. Methods In a randomized, multicenter (12 sites) clinical trial, 114 infants with a unilateral congenital cataract were assigned to undergo cataract surgery between 1 to 6 months of age either with or without primary IOL implantation. Contact lenses were used to correct aphakia in patients who did not receive IOLs. Grating visual acuity was tested at 1 year of age by a masked traveling examiner. Main Outcome Measure Grating visual acuity at 1 year of age. Results The median logMAR visual acuity was not significantly different between the treated eyes in the 2 groups (contact lens group, 0.80; IOL group, 0.97; P = .19). More patients in the IOL group underwent 1 or more additional intraocular operations than patients in the contact lens group (63% vs 12%; P < .001). Most of these additional operations were performed to clear lens reproliferation and pupillary membranes from the visual axis. Conclusions There was no statistically significant difference in grating visual acuity at age 1 year between the IOL and contact lens groups; however, additional intraocular operations were performed more frequently in the IOL group. Application to Clinical Practice Until longer-term follow-up data are available, caution should be exercised when performing IOL implantation in children aged 6 months or younger given the higher incidence of adverse events and the absence of an improved short-term visual outcome compared with contact lens use. Trial Registration clinicaltrials.gov Identifier: NCT00212134 Published online May 10, 2010 (doi:10.1001/archophthalmol.2010.101).
Evidence of Corneal Lymphangiogenesis in Dry Eye Disease: A Potential Link to Adaptive Immunity? [Clinical Sciences] :
Objective To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b⁺/LYVE-1⁺ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II^hi) antigen-presenting cells to the lymphoid compartment. Results Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P < .001) and lymphatic caliber (P < .02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b⁺/LYVE-1⁺ monocytic cells to the cornea and homing of mature CD11b⁺ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.
Meta-analysis of the Efficacy and Safety of {alpha}2-Adrenergic Agonists, {beta}-Adrenergic Antagonists, and Topical Carbonic Anhydrase Inhibitors With Prostaglandin Analogs [Clinical Sciences] :
Objective To perform a meta-analysis to estimate the intraocular pressure (IOP)–lowering efficacy and safety of ₂-adrenergic agonists (AAs), β-adrenergic antagonists (BBs), and topical carbonic anhydrase inhibitors (TCAIs) when used in combination with a prostaglandin analog (PGA). Methods MEDLINE, Embase, and the Cochrane Controlled Trials Register were systematically searched for relevant articles in April 2009. Ten observer-masked randomized clinical trials that reported baseline IOP while receiving PGA monotherapy and follow-up IOP while receiving combination therapy were identified. The pooled IOP-lowering efficacy achieved with each class of adjunctive agent was calculated using random-effects models. The frequencies of adverse events were pooled across studies and compared using Fisher exact test. Results Mean diurnal IOP reduction achieved in all 3 groups was statistically similar (P = .22). At trough, IOP reduction was greater in the TCAI (P < .001) and BB (P < .001) groups than in the AA group. Peak IOP reduction was similar in the 3 groups (P = .66). Eye or eyelid pain or burning and xerostomia were significantly more common in the AA group. Fatigue, weakness, or dizziness was more common in the AA and BB groups compared with the TCAI group. Taste disturbance was significantly more common in the TCAI group. Conclusions All 3 classes are similarly effective in lowering mean diurnal IOP when used in combination with PGAs. The AA class is statistically significantly less effective in reducing IOP at trough compared with BBs and TCAIs. The types of adverse events that were identified varied among the different classes of adjunctive therapies.
Economic Evaluation of Toric Intraocular Lens: A Short- and Long-term Decision Analytic Model [Clinical Sciences] :
Objective To assess the economic value of improved uncorrected visual acuity among patients with cataract and preexisting astigmatism treated with toric intraocular lenses (IOLs) compared with conventional monofocal IOLs. Methods We developed a decision analytic model of hypothetical patients with preexisting astigmatism. We examined costs and outcomes among patients 65 years and older with cataract and preexisting astigmatism (1.5-3.0 diopters) who were receiving either toric or conventional IOLs with and without intraoperative refractive correction (IRC). Data were obtained from the literature and from a survey of 60 US ophthalmologists. Total medical costs of bilateral treatment were calculated for the first posttreatment year and remaining lifetime. Cost-effectiveness and cost-utility outcomes were computed. Future costs and utilities were discounted by 3%. Results A larger proportion of patients receiving toric IOLs achieved distance vision spectacle independence (67%) and uncorrected visual acuity of 20/25 or better OU (53%) compared with conventional IOLs with (63% and 48%, respectively) or without IRC (53% and 44%, respectively), resulting in fewer future vision corrections. Toric IOLs provided an additional 10.20 quality-adjusted life years (QALYs) compared with conventional IOLs with (10.14 QALYs) and without IRC (10.10 QALYs). Higher first-year costs of the toric IOL ($5739) compared with the conventional IOL with ($5635) or without ($4687) IRC were offset by lifetime cost savings of $34 per patient, $393 per patient achieving uncorrected visual acuity of 20/25 or better, and $349 per QALY compared with the conventional IOL without IRC. Conclusions Toric IOLs reduce lifetime economic costs by reducing the need for glasses or contact lenses following cataract removal. These results can inform physicians and patients regarding the value of toric IOLs in the treatment of cataract and preexisting astigmatism.
Refractive Outcomes of Lens-Sparing Vitrectomy for Retinopathy of Prematurity [Clinical Sciences] :
Objective To evaluate the refractive outcomes of 3-port lens-sparing vitrectomy (LSV) for subtotal retinal detachments owing to retinopathy of prematurity. Methods The study included 9 infants who had undergone complete ablative laser treatment for threshold retinopathy of prematurity in both eyes, subsequently developed stage 4A retinal detachment in 1 eye for which they underwent LSV, and maintained complete retinal attachment bilaterally. Eyes that underwent LSV were compared with fellow eyes. Cycloplegic refraction was performed, and corneal curvature, axial length, lens thickness, lens position, and anterior chamber depth were measured. Results Significantly less myopia was present in eyes that had undergone LSV compared with control eyes (mean spherical equivalent, –6.78 vs –10.33 diopter [D]; P < .001). The reduced myopia in LSV eyes was predominantly owing to increased anterior chamber depth (mean, 3.81 vs 2.96 mm; P < .001) and a more posterior position of the lens (mean, 5.58 vs 4.63 mm; P < .001). There was a minor contribution from reduced corneal power in LSV eyes (mean, 43.90 vs 44.20 D; P = .02). There was no significant difference in axial length, lens thickness, or lens power between LSV and control eyes. Conclusions Infant eyes undergoing 3-port LSV for stage 4A retinopathy of prematurity develop less myopia than fellow eyes treated with ablative laser alone. The difference is owing to posterior displacement of the lens, with a smaller contribution from reduced corneal power. The reduction in myopia may explain the excellent functional outcomes following 3-port LSV for stage 4A retinopathy of prematurity.
Computer-Assisted Measurement of Retinal Vascular Width and Tortuosity in Retinopathy of Prematurity [Clinical Sciences] :
Objectives To validate the accuracy of ROPtool software in measuring retinal vascular width and tortuosity in a large image set compared with expert diagnoses. Methods Tortuosity and dilation indexes generated by ROPtool were compared with 3 expert consensus grades of normal, pre-plus, or plus disease for 368 quadrants in 92 RetCam (Clarity Medical Systems, Pleasanton, California) fundus images. Sensitivity and specificity of ROPtool software in diagnosing tortuosity and dilation sufficient for plus and pre-plus disease were calculated. These measures were compared with individual accuracies of 3 experienced pediatric ophthalmologists. Results The mean tortuosity indexes for expert-diagnosed categories of normal, pre-plus, and plus disease were 7.04, 18.73, and 34.62, respectively (P < .001), and the mean dilation indexes were 9.63, 12.05, and 13.61, respectively (P < .001). When optimal tortuosity and dilation index thresholds (from receiver operating characteristic curves) were applied, resultant sensitivity and specificity were 0.913 and 0.863, respectively, for plus tortuosity and 0.782 and 0.840, respectively, for plus dilation. These values were comparable to the performance of examiners judged against the same expert panel. Conclusion ROPtool version 2.1.5 accurately measures tortuosity and dilation of posterior pole blood vessels in RetCam images, corresponding well with expert diagnostic categories of normal, pre-plus, and plus disease and performing comparably to experienced examiners.
Clinical Features of Tuberculous Serpiginouslike Choroiditis in Contrast to Classic Serpiginous Choroiditis [Clinical Sciences] :
Objective To compare distinctive clinical features of presumed tuberculous serpiginouslike choroiditis (Tb-SLC) with classic serpiginous choroiditis (SC) in patients living in a region that is nonendemic for tuberculosis. Methods Retrospective comparative analysis of clinical features of 5 patients with recurrent Tb-SLC and 5 with SC. Results All patients with recurrent Tb-SLC primarily emigrated from areas highly endemic for tuberculosis and had been unsuccessfully treated with steroids/immunosuppressive agents. Results of uveitis investigations were negative except for positive tuberculin skin test results. These patients received oral tuberculostatic drugs, without recurrences (follow-up, 6-91 months). The ocular involvement in Tb-SLC was mostly unilateral, with multiple irregular serpiginoid lesions involving the posterior pole and periphery but usually sparing the juxtapapillary area. All 5 cases had inflammatory cells in the vitreous. Patients with SC were from areas nonendemic for tuberculosis, had negative uveitis workup findings (including tuberculin skin test results), and were successfully managed with steroids/immunosuppressive agents (follow-up, 6-72 months) with no recurrence. Ocular involvement in SC was usually bilateral, rarely multifocal, and primarily involved the posterior pole, especially around the optic disc and extending contiguously to the macula. No patient with SC presented with vitritis. Conclusion In areas nonendemic for tuberculosis, SC can be clinically differentiated from Tb-SLC. Patients with Tb-SLC come from highly endemic regions, show significant vitritis, and often present with multifocal lesions in the posterior pole and periphery. Cases of SC, in contrast, reveal minimal or no vitritis and frequently show bilateral involvement with larger solitary lesions extending primarily from the juxtapapillary area and sparing the periphery.
Halo Nevus of the Choroid in 150 Patients: The 2010 Henry van Dyke Lecture [Clinical Sciences] :
Objective To evaluate choroidal halo nevus. Methods We performed a retrospective medical record review on all patients with a clinical diagnosis of choroidal halo nevus treated at the Ocular Oncology Service at Wills Eye Institute from April 1, 1974, through June 30, 2008. Their clinical characteristics and natural history were studied. Results The choroidal halo nevus showed 2 components, including a distinct central pigmented region surrounded by a yellow halo. Of the 150 patients, 107 (71.3%) were women and 43 (28.7%) were men; and 149 (99.3%) were white, with a median age at presentation of 54 years. Autoimmune disorders were found in 4 patients (2.7%), a rate similar to the prevalence in the US population (2.7% vs 3.1%, P = .74). Preexistent cutaneous melanoma was found in 5 patients (3.3%), which was significantly more prevalent than the rate for the US population (3.3% vs 0.3%, P < .001). The halo was peripheral in 139 patients (92.7%) and slightly internal in 11 (7.3%). Two patients (1.3%) had multifocal halo nevi. The nevus location was superior in 31 patients (20.7%), temporal in 43 (28.7%), inferior in 29 (19.3%), nasal in 27 (18.0%), and macular in 20 (13.3%). Related features included drusen in 85 patients (56.7%), subretinal fluid in 21 (14.0%), orange pigment in 13 (8.7%), and retinal pigment epithelial atrophy in 15 (10.0%). There were no intraocular inflammatory findings. Of the 110 patients with nevi with follow-up, growth into melanoma occurred in 4 patients (3.6%) at a median interval of 41 months. Conclusions Halo nevus is a variant of choroidal nevus that has a brown center and yellow halo. No relationship was found with autoimmune disorders, but a relationship with previous cutaneous melanoma is possible.
Review of 676 Second Primary Tumors in Patients With Retinoblastoma: Association Between Age at Onset and Tumor Type [Clinical Sciences] :
Objective To obtain a more accurate understanding of second primary tumors (SPTs) by analyzing a large number of SPTs from the published literature. Methods A literature search was performed to identify published cases of SPTs in patients with retinoblastoma. Patient age, radiation field, tumor location, and tumor type were analyzed for statistical association. Results The study included 676 SPTs in 602 patients. Median age at diagnosis of SPT was 13.0 years (range, 0.3-60.4 years) for all SPTs, 2.7 years for midline intracranial primitive neuroectodermal tumors, 13.0 years for sarcomas, 27.0 years for melanomas, and 29.0 years for carcinomas. The median age at which SPTs occurred inside the radiation field was younger than that for SPTs occurring outside the radiation field or in patients who did not undergo irradiation (P < .001). Sarcomas occurred more commonly inside the radiation field (P < .001). Melanomas, lipomas, leukemias, and lymphomas occurred more commonly outside the radiation field or in patients who did not undergo irradiation (P < .001). Conclusions Retinoblastoma patients pass through multiple windows of susceptibility to specific SPTs. This information will aid health care providers in monitoring this high-risk group, and it provides new insights for studying the underlying genetic predisposition to SPTs.
Survival in Patients With Presymptomatic Diagnosis of Metastatic Uveal Melanoma [Clinical Sciences] :
Objective To determine if patients diagnosed as having metastatic uveal melanoma before the onset of symptoms experience more favorable survival outcomes than patients diagnosed after the onset of symptoms. Methods A retrospective cohort study was performed among 90 patients who were diagnosed as having metastatic uveal melanoma after proton beam irradiation by routine surveillance testing (asymptomatic group) compared with 259 patients who were diagnosed as having metastatic uveal melanoma after development of symptoms (symptomatic group). The median survival times and cumulative rates of melanoma-related death after diagnosis of metastasis were compared between the 2 groups. Results No differences were noted between groups in known prognostic factors for melanoma-related death, including age and tumor size. Cumulative rates of melanoma-related death were higher for patients in the symptomatic group vs the asymptomatic group (P < .001, log-rank test) owing to differences in mortality observed in the first year after diagnosis of metastasis (87.8% vs 68.5%). By the second year after diagnosis of metastasis, cumulative rates had reached 90% or higher in both groups. The median time to melanoma-related death after primary tumor diagnosis was 40.6 months in the asymptomatic group vs 45.1 months in the symptomatic group (P = .61). Conclusion Presymptomatic detection of metastatic uveal melanoma by routine surveillance testing seems to confer a survival advantage only in the first year after diagnosis of metastasis, which is likely because of lead-time bias.
Induction of Rapid and Highly Efficient Expression of the Human ND4 Complex I Subunit in the Mouse Visual System by Self-complementary Adeno-Associated Virus [Laboratory Sciences] :
Objective To demonstrate the high efficiency and rapidity of allotopic expression of a normal human ND4 subunit of complex I in the vertebrate retina using a self-complementary adeno-associated virus (scAAV) vector for ocular gene delivery to treat acute visual loss in Leber hereditary optic neuropathy (LHON). Methods The nuclear-encoded human ND4 subunit fused to the P1 isoform of subunit C of adenosine triphosphate synthase (ATPc) mitochondrial targeting sequence and FLAG epitope was packaged in scAAV2 capsids or single-stranded (ss) AAV2 capsids. These constructs were injected into the vitreous cavities of mice. The contralateral eyes were injected with scAAV–green fluorescent protein (GFP). One week later, pattern electroretinograms and gene expression of the human ND4 subunit and GFP were evaluated. Quantitative analysis of ND4FLAG-injected eyes was assessed relative to Thy1.2-labeled retinal ganglion cells (RGCs). Results Pattern electroretinogram amplitudes remained normal in eyes inoculated with scAAV-ND4FLAG, ssAAV-ND4FLAG, and GFP. Confocal microscopy revealed the typical perinuclear mitochondrial expression of scAAV-ND4FLAG in almost the entire retinal flat mount. In contrast, scAAV-GFP expression was cytoplasmic and nuclear. Relative to Thy1.2-positive RGCs, quantification of scAAV-ND4FLAG–positive RGCs was 91% and that of ssAAV-ND4FLAG–positive RGCs was 51%. Conclusion Treatment of acute visual loss due to LHON may be possible with a normal human ND4 subunit gene of complex I, mutated in most cases of LHON, when delivered by an scAAV vector. Clinical Relevance Unlike most retinal degenerations that result in slowly progressive loss of vision over many years, LHON due to mutated mitochondrial DNA results in apoplectic, bilateral severe and usually irreversible visual loss. For rescue of acute visual loss in LHON, a highly efficient and rapid gene expression system is required.
Intravitreous Bevacizumab Injection: An Experimental Study in New Zealand White Rabbits [Laboratory Sciences] :
Objectives To determine the effects of intraocular pressure (IOP) and needle diameter on the amount of reflux after intravitreous bevacizumab injection. Methods Prospective randomized interventional study. Twelve New Zealand white rabbits weighing approximately 2.5 to 3.5 kg each were randomized 1:1 to group 1 or group 2. Bevacizumab stained with trypan blue was used for intravitreous injection. To lower the IOP, eyes in group 2 underwent anterior chamber paracentesis before intravitreous injection. Two eyes in each group were injected using 27-, 30-, or 32-gauge needles. If a subconjunctival bleb formed after intravitreous injection, its diameter was measured using a caliper. Results The median IOP in group 1 was 17.5 mm Hg. Eyes injected using 27-gauge and 30-gauge needles showed stained subconjunctival blebs with median sizes of 3 mm and 1.7 mm, respectively; eyes injected using 32-gauge needles showed no subconjunctival bleb formation. The median IOP in group 2 was 10.3 mm Hg. Eyes injected using 27-gauge needles showed stained subconjunctival blebs with a median size of 0.7 mm, and eyes injected using 30-gauge and 32-gauge needles showed no subconjunctival bleb formation. Conclusion Decreasing the IOP before intravitreous injection and using a smaller-gauge needle reduce the risk of drug reflux after intravitreous bevacizumab injection. Clinical Relevance Intravitreous injection is an increasingly common route of drug delivery to treat ocular diseases. Techniques that maximize bioavailability are examined in this study.
Attenuation of Iodine 125 Radiation With Vitreous Substitutes in the Treatment of Uveal Melanoma [Laboratory Sciences] :
Objective To demonstrate attenuation of radiation from iodine 125 (¹²⁵I) to intraocular structures using liquid vitreous substitutes. Methods Four candidate vitreous substitutes were tested for attenuation using empirical measurement and theoretical calculation. In vitro and ex vivo cadaveric dosimetry measurements were obtained with lithium fluoride thermoluminescent dosimeters to demonstrate the attenuation effect of vitreous substitution during ¹²⁵I simulated plaque brachytherapy. Theoretical dosimetry calculations were based on Monte Carlo simulation. Results In a cylindrical phantom at a 17-mm depth, liquid vitreous substitutes as compared with saline showed significant reduction of radiation penetration (48% for 1000-centistoke [cSt] silicone oil [polydimethyl-n-siloxane], 47% for 5000-cSt silicone oil [polydimethyl-n-siloxane], 40% for heavy oil [perfluorohexyloctane/polydimethyl-n-siloxane], and 35% for perfluorocarbon liquid [perfluoro-n-octane]). Human cadaveric ex vivo measurements demonstrated a 1000-cSt silicone oil to saline dose ratio of 35%, 52%, 55%, and 48% at arc lengths of 7.6, 10.6, 22.3, and 28.6 mm from the plaque edge, respectively, along the surface of the globe. Monte Carlo simulation of a human globe projected attenuation as high as 57% using 1000-cSt silicone oil. Conclusions Intraocular vitreous substitutes including silicone oil, heavy oil, and perfluorocarbon liquid attenuate the radiation dose from ¹²⁵I. Cadaveric ex vivo measurements and Monte Carlo simulation both demonstrate radiation attenuation using 1000-cSt silicone oil at distances corresponding to vital ocular structures. Clinical Relevance Attenuation of radiation with silicone oil endotamponade in the treatment of uveal melanoma may significantly reduce radiation-induced injury to vital ocular structures.
Use of Visual Acuity to Screen for Significant Refractive Errors in Adolescents: Is It Reliable? [Epidemiology] :
Objective To detect significant refractive error in a population-based random cluster sample of 12-year-old schoolchildren by using sensitivity and specificity of uncorrected visual acuity (VA). Methods The Sydney Myopia Study randomly selected 21 secondary schools stratified by socioeconomic status. All year 7 students (mean age, 12.7 years) were invited to participate. We tested VA monocularly, unaided at 2.44 m, using a retroilluminated logMAR chart. Cycloplegic autorefraction (induced with instillation of cyclopentolate hydrochloride, 1%) was used to define clinically significant refractive error as a spherical equivalent of –1.00 diopters (D) or less for myopia; at least +2.00 D for hyperopia; and –1.00 D or less cylinder power for astigmatism. Results Data for both eyes were pooled for a total of 4497 observations. The sensitivity and specificity for all clinically significant refractive errors at the best VA cutoff level of 53 letters (6/6_–2) were 72.2% and 93.3%, respectively. Myopia had the highest sensitivity and specificity of any of the refractive errors for detection using VA (97.8% and 97.1%, respectively, for a 45-letter VA cutoff [6/9.5]). The best VA cutoffs for hyperopia and astigmatism were 57 (6/6₊₂) and 55 (6/6) letters, respectively, with sensitivities of 69.2% and 77.4%, respectively, and specificities of 58.1% and 75.4%, respectively. Conclusions In this adolescent group, a VA cutoff of 6/9.5 or less detects myopic refractive error reliably. However, there is no reliable VA cutoff for clinically significant hyperopia or astigmatism. Improved VA screening methods are required to improve detection of these conditions. Even so, with the methods described herein, the prevalence of uncorrected VA may provide a reasonably accurate estimate of the prevalence of myopia.
Refractive Error, Axial Dimensions, and Primary Open-Angle Glaucoma: The Singapore Malay Eye Study [Epidemiology] :
Objective To explore the relationship of refractive error and ocular biometry with primary open-angle glaucoma (POAG) in the Malay population. Methods The Singapore Malay Eye Study is a population-based cross-sectional survey that examined 3280 persons (78.7% response) aged 40 to 80 years. Participants underwent a standardized clinical examination including slitlamp biomicroscopy, Goldmann applanation tonometry, refraction, dilated optic disc assessment, and measurement of axial length (AL) and central corneal thickness (CCT). Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. Results After adjusting for possible confounders, persons with moderate or high myopia (less than –4.0 diopters, right eyes) were more likely to have POAG (odds ratio [OR], 2.87; 95% confidence interval, 1.09-7.53); this association remained significant after controlling for CCT (2.80; 1.07-7.37). Longer AL was associated with POAG (ORs, 2.49, 3.61, and 2.88, comparing quartiles 2, 3, and 4, respectively, with quartile 1 of AL; P = .03 for trend). If CCT was controlled for, persons with AL in quartile 4 were 3 times more likely to have POAG (OR, 3.00; 95% confidence interval, 1.09-8.24) than those in quartile 1. Conclusion This population-based study in Singapore shows an association of moderate myopia and increasing AL with POAG independent of other factors, including CCT.
Misrepresentation by Ophthalmology Residency Applicants [Socioeconomics and Health Services] :
Objectives To determine the percentage of publication misrepresentation among applicants to an ophthalmology residency, to compare that percentage with published percentages from other specialties, and to compare the number of US-trained applicants vs non–US-trained applicants found to misrepresent published articles. Methods Published articles in peer-reviewed journals listed on residency applications to the Jones Eye Institute from October 10, 2000, to December 1, 2004, were searched, excluding applications that were unavailable or were from current residents and faculty. The type of misrepresentation of published articles and the country of medical school training were recorded. Compared were US-trained applicants vs non–US-trained applicants to determine which group was more likely to list published articles and which group was more likely to have a misrepresented published article. Results Eight hundred twenty-one of 852 applications (96.4%) were reviewed. Five hundred fifty applicants (67.0%) were from US medical schools, and 271 applicants (33.0%) were from non-US medical schools. Two hundred one applicants (24.5%) listed peer-reviewed published articles. Misrepresentation of published articles was found in 15 applicants (5 US trained and 10 non-US trained). The mean percentage of applicants with misrepresentation per applicant pool was 1.9%, while the mean percentage per applicants listing published articles was 8.1%. The most common misrepresentation found was self-promotion on the author list (50.0%), followed by omission of other authors (25.0%), nonexistent articles (12.5%), and nonauthorship (12.5%). Foreign medical graduates were more likely to list published articles (P = .008) and to have a misrepresented published article (P = .01). Conclusions Ophthalmology has one of the lowest reported percentages of applicant publication misrepresentation in the literature. Foreign medical graduates were more likely to list published articles and to misrepresent published articles. Self-promotion on the author list was the most common type of misrepresentation found. Residency program directors should request copies of published articles from interviewing applicants.
Chandelier Retroillumination-Assisted Cataract Extraction in Eyes With Vitreous Hemorrhage [Surgical Technique] :
We describe the surgical technique of using an illuminated infusion chandelier for cataract extraction in patients with absent red reflex due to vitreous hemorrhage. A 23-gauge illuminated infusion chandelier was used for cataract extraction in 6 consecutive patients (6 eyes) who underwent combined surgery: phacoemulsification and 23-gauge sutureless vitrectomy. During surgery, the light from the illuminated infusion chandelier was used to enhance the red reflex and to better visualize the lens structure and capsule. Continuous curvilinear capsulorhexis and phacoemulsification were successfully performed. Capsular polishing was also performed safely and easily. The posterior capsule remained intact and the intraocular lens was inserted into the bag in all cases. Thus, the use of the 23-gauge illuminated infusion chandelier can improve visualization of the lens structure and capsule, thereby facilitating successful cataract extraction in select patients with vitreous hemorrhage.

Glycemic and Blood Pressure Control in an Asian Malay Population With Diabetes and Diabetic Retinopathy [Epidemiology] :
Objective To examine the prevalence of and factors associated with suboptimal glycemic and blood pressure (BP) control in a Malay population with diabetes mellitus in Singapore.Methods The Singapore Malay Eye Study was a population-based survey of 3280 Malay individuals (78.7% response rate) aged 40 to 80 years. Diabetes was defined as a nonfasting glucose level of 200 mg/dL or greater, use of diabetic medication, or physician diagnosis. Diabetic retinopathy (DR) was graded from retinal photographs using the modified Airlie House classification. Optimal control was defined as a hemoglobin A_1c level of less than 7% and BP of 130/80 mm Hg or lower.Results In participants with diabetes (n = 768), only 26.9% had optimal glycemic and 13.4% optimal BP control, respectively. In those with DR (n = 272), rates of optimal glycemic and BP control were even lower (17.4% and 10.3%, respectively). After adjusting for age, sex, socioeconomic status, and other factors, compared with participants with optimal glycemic control, those with suboptimal control were younger (P = .005), more likely to be unaware of their diabetes status (P < .001), and taking medication for diabetes (P < .001) and had higher levels of total cholesterol (P = .009) and DR (P < .001). After adjusting for similar risk factors, compared with participants with optimal BP control, those with suboptimal BP control were older (P = .006) and more likely to have higher total cholesterol levels (P = .002), BMIs (P = .04), and DR (P = .02).Conclusions In this Asian Malay population with diabetes, more than three-quarters had poor glycemic and BP control. Strategies to improve awareness and implement evidence-based guidelines are needed to reduce the effect and burden of diabetic complications in Asia.Published online July 12, 2010 (doi:10.1001/archophthalmol.2010.168).
Selected Sun-Sensitizing Medications and Incident Cataract [Clinical Sciences] :
Objective To examine the relationship between the use of sun-sensitizing medications and cumulative incidence of age-related cataract.Methods Sun exposure was estimated from residential history of adults in the Midwestern community of Beaver Dam, Wisconsin, which permitted calculation of Wisconsin sun-years at the baseline examination. Medication history was reported at each examination. Cataract presence was determined by standardized lens photographs that were taken at each examination and graded according to standard protocols.Results No significant effects were noted of Wisconsin sun-year exposure or use of sun-sensitizing medications on the cumulative incidence of any type of age-related cataract when controlling for age and sex. However, an interaction term combining Wisconsin sun-years and use of any sun-sensitizing medication was significant (P = .04) such that risk of cortical cataract is significantly higher for the joint risk group. Further controlling for the presence of diabetes mellitus, history of heavy drinking, and hat or sunglasses use did not alter the relationships.Conclusions Data suggest that the use of sun-sensitizing medications interacts with sun exposure to influence the risk of cortical cataract, a common age-related cataract. If confirmed, this finding may have important implications for medication use.Published online June 14, 2010 (doi:10.1001/archophthalmol.2010.138).
About This Journal [About This Journal]
A Randomized Clinical Trial Comparing Contact Lens With Intraocular Lens Correction of Monocular Aphakia During Infancy: Grating Acuity and Adverse Events at Age 1 Year [Clinical Trial] :
Objective To compare the visual outcomes and adverse events of contact lens with primary intraocular lens (IOL) correction of monocular aphakia during infancy. Methods In a randomized, multicenter (12 sites) clinical trial, 114 infants with a unilateral congenital cataract were assigned to undergo cataract surgery between 1 to 6 months of age either with or without primary IOL implantation. Contact lenses were used to correct aphakia in patients who did not receive IOLs. Grating visual acuity was tested at 1 year of age by a masked traveling examiner. Main Outcome Measure Grating visual acuity at 1 year of age. Results The median logMAR visual acuity was not significantly different between the treated eyes in the 2 groups (contact lens group, 0.80; IOL group, 0.97; P = .19). More patients in the IOL group underwent 1 or more additional intraocular operations than patients in the contact lens group (63% vs 12%; P < .001). Most of these additional operations were performed to clear lens reproliferation and pupillary membranes from the visual axis. Conclusions There was no statistically significant difference in grating visual acuity at age 1 year between the IOL and contact lens groups; however, additional intraocular operations were performed more frequently in the IOL group. Application to Clinical Practice Until longer-term follow-up data are available, caution should be exercised when performing IOL implantation in children aged 6 months or younger given the higher incidence of adverse events and the absence of an improved short-term visual outcome compared with contact lens use. Trial Registration clinicaltrials.gov Identifier: NCT00212134 Published online May 10, 2010 (doi:10.1001/archophthalmol.2010.101).
Evidence of Corneal Lymphangiogenesis in Dry Eye Disease: A Potential Link to Adaptive Immunity? [Clinical Sciences] :
Objective To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b⁺/LYVE-1⁺ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II^hi) antigen-presenting cells to the lymphoid compartment. Results Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P < .001) and lymphatic caliber (P < .02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b⁺/LYVE-1⁺ monocytic cells to the cornea and homing of mature CD11b⁺ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.
Meta-analysis of the Efficacy and Safety of {alpha}2-Adrenergic Agonists, {beta}-Adrenergic Antagonists, and Topical Carbonic Anhydrase Inhibitors With Prostaglandin Analogs [Clinical Sciences] :
Objective To perform a meta-analysis to estimate the intraocular pressure (IOP)–lowering efficacy and safety of ₂-adrenergic agonists (AAs), β-adrenergic antagonists (BBs), and topical carbonic anhydrase inhibitors (TCAIs) when used in combination with a prostaglandin analog (PGA). Methods MEDLINE, Embase, and the Cochrane Controlled Trials Register were systematically searched for relevant articles in April 2009. Ten observer-masked randomized clinical trials that reported baseline IOP while receiving PGA monotherapy and follow-up IOP while receiving combination therapy were identified. The pooled IOP-lowering efficacy achieved with each class of adjunctive agent was calculated using random-effects models. The frequencies of adverse events were pooled across studies and compared using Fisher exact test. Results Mean diurnal IOP reduction achieved in all 3 groups was statistically similar (P = .22). At trough, IOP reduction was greater in the TCAI (P < .001) and BB (P < .001) groups than in the AA group. Peak IOP reduction was similar in the 3 groups (P = .66). Eye or eyelid pain or burning and xerostomia were significantly more common in the AA group. Fatigue, weakness, or dizziness was more common in the AA and BB groups compared with the TCAI group. Taste disturbance was significantly more common in the TCAI group. Conclusions All 3 classes are similarly effective in lowering mean diurnal IOP when used in combination with PGAs. The AA class is statistically significantly less effective in reducing IOP at trough compared with BBs and TCAIs. The types of adverse events that were identified varied among the different classes of adjunctive therapies.
Economic Evaluation of Toric Intraocular Lens: A Short- and Long-term Decision Analytic Model [Clinical Sciences] :
Objective To assess the economic value of improved uncorrected visual acuity among patients with cataract and preexisting astigmatism treated with toric intraocular lenses (IOLs) compared with conventional monofocal IOLs. Methods We developed a decision analytic model of hypothetical patients with preexisting astigmatism. We examined costs and outcomes among patients 65 years and older with cataract and preexisting astigmatism (1.5-3.0 diopters) who were receiving either toric or conventional IOLs with and without intraoperative refractive correction (IRC). Data were obtained from the literature and from a survey of 60 US ophthalmologists. Total medical costs of bilateral treatment were calculated for the first posttreatment year and remaining lifetime. Cost-effectiveness and cost-utility outcomes were computed. Future costs and utilities were discounted by 3%. Results A larger proportion of patients receiving toric IOLs achieved distance vision spectacle independence (67%) and uncorrected visual acuity of 20/25 or better OU (53%) compared with conventional IOLs with (63% and 48%, respectively) or without IRC (53% and 44%, respectively), resulting in fewer future vision corrections. Toric IOLs provided an additional 10.20 quality-adjusted life years (QALYs) compared with conventional IOLs with (10.14 QALYs) and without IRC (10.10 QALYs). Higher first-year costs of the toric IOL ($5739) compared with the conventional IOL with ($5635) or without ($4687) IRC were offset by lifetime cost savings of $34 per patient, $393 per patient achieving uncorrected visual acuity of 20/25 or better, and $349 per QALY compared with the conventional IOL without IRC. Conclusions Toric IOLs reduce lifetime economic costs by reducing the need for glasses or contact lenses following cataract removal. These results can inform physicians and patients regarding the value of toric IOLs in the treatment of cataract and preexisting astigmatism.
Refractive Outcomes of Lens-Sparing Vitrectomy for Retinopathy of Prematurity [Clinical Sciences] :
Objective To evaluate the refractive outcomes of 3-port lens-sparing vitrectomy (LSV) for subtotal retinal detachments owing to retinopathy of prematurity. Methods The study included 9 infants who had undergone complete ablative laser treatment for threshold retinopathy of prematurity in both eyes, subsequently developed stage 4A retinal detachment in 1 eye for which they underwent LSV, and maintained complete retinal attachment bilaterally. Eyes that underwent LSV were compared with fellow eyes. Cycloplegic refraction was performed, and corneal curvature, axial length, lens thickness, lens position, and anterior chamber depth were measured. Results Significantly less myopia was present in eyes that had undergone LSV compared with control eyes (mean spherical equivalent, –6.78 vs –10.33 diopter [D]; P < .001). The reduced myopia in LSV eyes was predominantly owing to increased anterior chamber depth (mean, 3.81 vs 2.96 mm; P < .001) and a more posterior position of the lens (mean, 5.58 vs 4.63 mm; P < .001). There was a minor contribution from reduced corneal power in LSV eyes (mean, 43.90 vs 44.20 D; P = .02). There was no significant difference in axial length, lens thickness, or lens power between LSV and control eyes. Conclusions Infant eyes undergoing 3-port LSV for stage 4A retinopathy of prematurity develop less myopia than fellow eyes treated with ablative laser alone. The difference is owing to posterior displacement of the lens, with a smaller contribution from reduced corneal power. The reduction in myopia may explain the excellent functional outcomes following 3-port LSV for stage 4A retinopathy of prematurity.
Computer-Assisted Measurement of Retinal Vascular Width and Tortuosity in Retinopathy of Prematurity [Clinical Sciences] :
Objectives To validate the accuracy of ROPtool software in measuring retinal vascular width and tortuosity in a large image set compared with expert diagnoses. Methods Tortuosity and dilation indexes generated by ROPtool were compared with 3 expert consensus grades of normal, pre-plus, or plus disease for 368 quadrants in 92 RetCam (Clarity Medical Systems, Pleasanton, California) fundus images. Sensitivity and specificity of ROPtool software in diagnosing tortuosity and dilation sufficient for plus and pre-plus disease were calculated. These measures were compared with individual accuracies of 3 experienced pediatric ophthalmologists. Results The mean tortuosity indexes for expert-diagnosed categories of normal, pre-plus, and plus disease were 7.04, 18.73, and 34.62, respectively (P < .001), and the mean dilation indexes were 9.63, 12.05, and 13.61, respectively (P < .001). When optimal tortuosity and dilation index thresholds (from receiver operating characteristic curves) were applied, resultant sensitivity and specificity were 0.913 and 0.863, respectively, for plus tortuosity and 0.782 and 0.840, respectively, for plus dilation. These values were comparable to the performance of examiners judged against the same expert panel. Conclusion ROPtool version 2.1.5 accurately measures tortuosity and dilation of posterior pole blood vessels in RetCam images, corresponding well with expert diagnostic categories of normal, pre-plus, and plus disease and performing comparably to experienced examiners.
Clinical Features of Tuberculous Serpiginouslike Choroiditis in Contrast to Classic Serpiginous Choroiditis [Clinical Sciences] :
Objective To compare distinctive clinical features of presumed tuberculous serpiginouslike choroiditis (Tb-SLC) with classic serpiginous choroiditis (SC) in patients living in a region that is nonendemic for tuberculosis. Methods Retrospective comparative analysis of clinical features of 5 patients with recurrent Tb-SLC and 5 with SC. Results All patients with recurrent Tb-SLC primarily emigrated from areas highly endemic for tuberculosis and had been unsuccessfully treated with steroids/immunosuppressive agents. Results of uveitis investigations were negative except for positive tuberculin skin test results. These patients received oral tuberculostatic drugs, without recurrences (follow-up, 6-91 months). The ocular involvement in Tb-SLC was mostly unilateral, with multiple irregular serpiginoid lesions involving the posterior pole and periphery but usually sparing the juxtapapillary area. All 5 cases had inflammatory cells in the vitreous. Patients with SC were from areas nonendemic for tuberculosis, had negative uveitis workup findings (including tuberculin skin test results), and were successfully managed with steroids/immunosuppressive agents (follow-up, 6-72 months) with no recurrence. Ocular involvement in SC was usually bilateral, rarely multifocal, and primarily involved the posterior pole, especially around the optic disc and extending contiguously to the macula. No patient with SC presented with vitritis. Conclusion In areas nonendemic for tuberculosis, SC can be clinically differentiated from Tb-SLC. Patients with Tb-SLC come from highly endemic regions, show significant vitritis, and often present with multifocal lesions in the posterior pole and periphery. Cases of SC, in contrast, reveal minimal or no vitritis and frequently show bilateral involvement with larger solitary lesions extending primarily from the juxtapapillary area and sparing the periphery.
Halo Nevus of the Choroid in 150 Patients: The 2010 Henry van Dyke Lecture [Clinical Sciences] :
Objective To evaluate choroidal halo nevus. Methods We performed a retrospective medical record review on all patients with a clinical diagnosis of choroidal halo nevus treated at the Ocular Oncology Service at Wills Eye Institute from April 1, 1974, through June 30, 2008. Their clinical characteristics and natural history were studied. Results The choroidal halo nevus showed 2 components, including a distinct central pigmented region surrounded by a yellow halo. Of the 150 patients, 107 (71.3%) were women and 43 (28.7%) were men; and 149 (99.3%) were white, with a median age at presentation of 54 years. Autoimmune disorders were found in 4 patients (2.7%), a rate similar to the prevalence in the US population (2.7% vs 3.1%, P = .74). Preexistent cutaneous melanoma was found in 5 patients (3.3%), which was significantly more prevalent than the rate for the US population (3.3% vs 0.3%, P < .001). The halo was peripheral in 139 patients (92.7%) and slightly internal in 11 (7.3%). Two patients (1.3%) had multifocal halo nevi. The nevus location was superior in 31 patients (20.7%), temporal in 43 (28.7%), inferior in 29 (19.3%), nasal in 27 (18.0%), and macular in 20 (13.3%). Related features included drusen in 85 patients (56.7%), subretinal fluid in 21 (14.0%), orange pigment in 13 (8.7%), and retinal pigment epithelial atrophy in 15 (10.0%). There were no intraocular inflammatory findings. Of the 110 patients with nevi with follow-up, growth into melanoma occurred in 4 patients (3.6%) at a median interval of 41 months. Conclusions Halo nevus is a variant of choroidal nevus that has a brown center and yellow halo. No relationship was found with autoimmune disorders, but a relationship with previous cutaneous melanoma is possible.
Review of 676 Second Primary Tumors in Patients With Retinoblastoma: Association Between Age at Onset and Tumor Type [Clinical Sciences] :
Objective To obtain a more accurate understanding of second primary tumors (SPTs) by analyzing a large number of SPTs from the published literature. Methods A literature search was performed to identify published cases of SPTs in patients with retinoblastoma. Patient age, radiation field, tumor location, and tumor type were analyzed for statistical association. Results The study included 676 SPTs in 602 patients. Median age at diagnosis of SPT was 13.0 years (range, 0.3-60.4 years) for all SPTs, 2.7 years for midline intracranial primitive neuroectodermal tumors, 13.0 years for sarcomas, 27.0 years for melanomas, and 29.0 years for carcinomas. The median age at which SPTs occurred inside the radiation field was younger than that for SPTs occurring outside the radiation field or in patients who did not undergo irradiation (P < .001). Sarcomas occurred more commonly inside the radiation field (P < .001). Melanomas, lipomas, leukemias, and lymphomas occurred more commonly outside the radiation field or in patients who did not undergo irradiation (P < .001). Conclusions Retinoblastoma patients pass through multiple windows of susceptibility to specific SPTs. This information will aid health care providers in monitoring this high-risk group, and it provides new insights for studying the underlying genetic predisposition to SPTs.
Survival in Patients With Presymptomatic Diagnosis of Metastatic Uveal Melanoma [Clinical Sciences] :
Objective To determine if patients diagnosed as having metastatic uveal melanoma before the onset of symptoms experience more favorable survival outcomes than patients diagnosed after the onset of symptoms. Methods A retrospective cohort study was performed among 90 patients who were diagnosed as having metastatic uveal melanoma after proton beam irradiation by routine surveillance testing (asymptomatic group) compared with 259 patients who were diagnosed as having metastatic uveal melanoma after development of symptoms (symptomatic group). The median survival times and cumulative rates of melanoma-related death after diagnosis of metastasis were compared between the 2 groups. Results No differences were noted between groups in known prognostic factors for melanoma-related death, including age and tumor size. Cumulative rates of melanoma-related death were higher for patients in the symptomatic group vs the asymptomatic group (P < .001, log-rank test) owing to differences in mortality observed in the first year after diagnosis of metastasis (87.8% vs 68.5%). By the second year after diagnosis of metastasis, cumulative rates had reached 90% or higher in both groups. The median time to melanoma-related death after primary tumor diagnosis was 40.6 months in the asymptomatic group vs 45.1 months in the symptomatic group (P = .61). Conclusion Presymptomatic detection of metastatic uveal melanoma by routine surveillance testing seems to confer a survival advantage only in the first year after diagnosis of metastasis, which is likely because of lead-time bias.
Induction of Rapid and Highly Efficient Expression of the Human ND4 Complex I Subunit in the Mouse Visual System by Self-complementary Adeno-Associated Virus [Laboratory Sciences] :
Objective To demonstrate the high efficiency and rapidity of allotopic expression of a normal human ND4 subunit of complex I in the vertebrate retina using a self-complementary adeno-associated virus (scAAV) vector for ocular gene delivery to treat acute visual loss in Leber hereditary optic neuropathy (LHON). Methods The nuclear-encoded human ND4 subunit fused to the P1 isoform of subunit C of adenosine triphosphate synthase (ATPc) mitochondrial targeting sequence and FLAG epitope was packaged in scAAV2 capsids or single-stranded (ss) AAV2 capsids. These constructs were injected into the vitreous cavities of mice. The contralateral eyes were injected with scAAV–green fluorescent protein (GFP). One week later, pattern electroretinograms and gene expression of the human ND4 subunit and GFP were evaluated. Quantitative analysis of ND4FLAG-injected eyes was assessed relative to Thy1.2-labeled retinal ganglion cells (RGCs). Results Pattern electroretinogram amplitudes remained normal in eyes inoculated with scAAV-ND4FLAG, ssAAV-ND4FLAG, and GFP. Confocal microscopy revealed the typical perinuclear mitochondrial expression of scAAV-ND4FLAG in almost the entire retinal flat mount. In contrast, scAAV-GFP expression was cytoplasmic and nuclear. Relative to Thy1.2-positive RGCs, quantification of scAAV-ND4FLAG–positive RGCs was 91% and that of ssAAV-ND4FLAG–positive RGCs was 51%. Conclusion Treatment of acute visual loss due to LHON may be possible with a normal human ND4 subunit gene of complex I, mutated in most cases of LHON, when delivered by an scAAV vector. Clinical Relevance Unlike most retinal degenerations that result in slowly progressive loss of vision over many years, LHON due to mutated mitochondrial DNA results in apoplectic, bilateral severe and usually irreversible visual loss. For rescue of acute visual loss in LHON, a highly efficient and rapid gene expression system is required.
Intravitreous Bevacizumab Injection: An Experimental Study in New Zealand White Rabbits [Laboratory Sciences] :
Objectives To determine the effects of intraocular pressure (IOP) and needle diameter on the amount of reflux after intravitreous bevacizumab injection. Methods Prospective randomized interventional study. Twelve New Zealand white rabbits weighing approximately 2.5 to 3.5 kg each were randomized 1:1 to group 1 or group 2. Bevacizumab stained with trypan blue was used for intravitreous injection. To lower the IOP, eyes in group 2 underwent anterior chamber paracentesis before intravitreous injection. Two eyes in each group were injected using 27-, 30-, or 32-gauge needles. If a subconjunctival bleb formed after intravitreous injection, its diameter was measured using a caliper. Results The median IOP in group 1 was 17.5 mm Hg. Eyes injected using 27-gauge and 30-gauge needles showed stained subconjunctival blebs with median sizes of 3 mm and 1.7 mm, respectively; eyes injected using 32-gauge needles showed no subconjunctival bleb formation. The median IOP in group 2 was 10.3 mm Hg. Eyes injected using 27-gauge needles showed stained subconjunctival blebs with a median size of 0.7 mm, and eyes injected using 30-gauge and 32-gauge needles showed no subconjunctival bleb formation. Conclusion Decreasing the IOP before intravitreous injection and using a smaller-gauge needle reduce the risk of drug reflux after intravitreous bevacizumab injection. Clinical Relevance Intravitreous injection is an increasingly common route of drug delivery to treat ocular diseases. Techniques that maximize bioavailability are examined in this study.
Attenuation of Iodine 125 Radiation With Vitreous Substitutes in the Treatment of Uveal Melanoma [Laboratory Sciences] :
Objective To demonstrate attenuation of radiation from iodine 125 (¹²⁵I) to intraocular structures using liquid vitreous substitutes. Methods Four candidate vitreous substitutes were tested for attenuation using empirical measurement and theoretical calculation. In vitro and ex vivo cadaveric dosimetry measurements were obtained with lithium fluoride thermoluminescent dosimeters to demonstrate the attenuation effect of vitreous substitution during ¹²⁵I simulated plaque brachytherapy. Theoretical dosimetry calculations were based on Monte Carlo simulation. Results In a cylindrical phantom at a 17-mm depth, liquid vitreous substitutes as compared with saline showed significant reduction of radiation penetration (48% for 1000-centistoke [cSt] silicone oil [polydimethyl-n-siloxane], 47% for 5000-cSt silicone oil [polydimethyl-n-siloxane], 40% for heavy oil [perfluorohexyloctane/polydimethyl-n-siloxane], and 35% for perfluorocarbon liquid [perfluoro-n-octane]). Human cadaveric ex vivo measurements demonstrated a 1000-cSt silicone oil to saline dose ratio of 35%, 52%, 55%, and 48% at arc lengths of 7.6, 10.6, 22.3, and 28.6 mm from the plaque edge, respectively, along the surface of the globe. Monte Carlo simulation of a human globe projected attenuation as high as 57% using 1000-cSt silicone oil. Conclusions Intraocular vitreous substitutes including silicone oil, heavy oil, and perfluorocarbon liquid attenuate the radiation dose from ¹²⁵I. Cadaveric ex vivo measurements and Monte Carlo simulation both demonstrate radiation attenuation using 1000-cSt silicone oil at distances corresponding to vital ocular structures. Clinical Relevance Attenuation of radiation with silicone oil endotamponade in the treatment of uveal melanoma may significantly reduce radiation-induced injury to vital ocular structures.
Use of Visual Acuity to Screen for Significant Refractive Errors in Adolescents: Is It Reliable? [Epidemiology] :
Objective To detect significant refractive error in a population-based random cluster sample of 12-year-old schoolchildren by using sensitivity and specificity of uncorrected visual acuity (VA). Methods The Sydney Myopia Study randomly selected 21 secondary schools stratified by socioeconomic status. All year 7 students (mean age, 12.7 years) were invited to participate. We tested VA monocularly, unaided at 2.44 m, using a retroilluminated logMAR chart. Cycloplegic autorefraction (induced with instillation of cyclopentolate hydrochloride, 1%) was used to define clinically significant refractive error as a spherical equivalent of –1.00 diopters (D) or less for myopia; at least +2.00 D for hyperopia; and –1.00 D or less cylinder power for astigmatism. Results Data for both eyes were pooled for a total of 4497 observations. The sensitivity and specificity for all clinically significant refractive errors at the best VA cutoff level of 53 letters (6/6_–2) were 72.2% and 93.3%, respectively. Myopia had the highest sensitivity and specificity of any of the refractive errors for detection using VA (97.8% and 97.1%, respectively, for a 45-letter VA cutoff [6/9.5]). The best VA cutoffs for hyperopia and astigmatism were 57 (6/6₊₂) and 55 (6/6) letters, respectively, with sensitivities of 69.2% and 77.4%, respectively, and specificities of 58.1% and 75.4%, respectively. Conclusions In this adolescent group, a VA cutoff of 6/9.5 or less detects myopic refractive error reliably. However, there is no reliable VA cutoff for clinically significant hyperopia or astigmatism. Improved VA screening methods are required to improve detection of these conditions. Even so, with the methods described herein, the prevalence of uncorrected VA may provide a reasonably accurate estimate of the prevalence of myopia.
Refractive Error, Axial Dimensions, and Primary Open-Angle Glaucoma: The Singapore Malay Eye Study [Epidemiology] :
Objective To explore the relationship of refractive error and ocular biometry with primary open-angle glaucoma (POAG) in the Malay population. Methods The Singapore Malay Eye Study is a population-based cross-sectional survey that examined 3280 persons (78.7% response) aged 40 to 80 years. Participants underwent a standardized clinical examination including slitlamp biomicroscopy, Goldmann applanation tonometry, refraction, dilated optic disc assessment, and measurement of axial length (AL) and central corneal thickness (CCT). Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. Results After adjusting for possible confounders, persons with moderate or high myopia (less than –4.0 diopters, right eyes) were more likely to have POAG (odds ratio [OR], 2.87; 95% confidence interval, 1.09-7.53); this association remained significant after controlling for CCT (2.80; 1.07-7.37). Longer AL was associated with POAG (ORs, 2.49, 3.61, and 2.88, comparing quartiles 2, 3, and 4, respectively, with quartile 1 of AL; P = .03 for trend). If CCT was controlled for, persons with AL in quartile 4 were 3 times more likely to have POAG (OR, 3.00; 95% confidence interval, 1.09-8.24) than those in quartile 1. Conclusion This population-based study in Singapore shows an association of moderate myopia and increasing AL with POAG independent of other factors, including CCT.
Misrepresentation by Ophthalmology Residency Applicants [Socioeconomics and Health Services] :
Objectives To determine the percentage of publication misrepresentation among applicants to an ophthalmology residency, to compare that percentage with published percentages from other specialties, and to compare the number of US-trained applicants vs non–US-trained applicants found to misrepresent published articles. Methods Published articles in peer-reviewed journals listed on residency applications to the Jones Eye Institute from October 10, 2000, to December 1, 2004, were searched, excluding applications that were unavailable or were from current residents and faculty. The type of misrepresentation of published articles and the country of medical school training were recorded. Compared were US-trained applicants vs non–US-trained applicants to determine which group was more likely to list published articles and which group was more likely to have a misrepresented published article. Results Eight hundred twenty-one of 852 applications (96.4%) were reviewed. Five hundred fifty applicants (67.0%) were from US medical schools, and 271 applicants (33.0%) were from non-US medical schools. Two hundred one applicants (24.5%) listed peer-reviewed published articles. Misrepresentation of published articles was found in 15 applicants (5 US trained and 10 non-US trained). The mean percentage of applicants with misrepresentation per applicant pool was 1.9%, while the mean percentage per applicants listing published articles was 8.1%. The most common misrepresentation found was self-promotion on the author list (50.0%), followed by omission of other authors (25.0%), nonexistent articles (12.5%), and nonauthorship (12.5%). Foreign medical graduates were more likely to list published articles (P = .008) and to have a misrepresented published article (P = .01). Conclusions Ophthalmology has one of the lowest reported percentages of applicant publication misrepresentation in the literature. Foreign medical graduates were more likely to list published articles and to misrepresent published articles. Self-promotion on the author list was the most common type of misrepresentation found. Residency program directors should request copies of published articles from interviewing applicants.
Chandelier Retroillumination-Assisted Cataract Extraction in Eyes With Vitreous Hemorrhage [Surgical Technique] :
We describe the surgical technique of using an illuminated infusion chandelier for cataract extraction in patients with absent red reflex due to vitreous hemorrhage. A 23-gauge illuminated infusion chandelier was used for cataract extraction in 6 consecutive patients (6 eyes) who underwent combined surgery: phacoemulsification and 23-gauge sutureless vitrectomy. During surgery, the light from the illuminated infusion chandelier was used to enhance the red reflex and to better visualize the lens structure and capsule. Continuous curvilinear capsulorhexis and phacoemulsification were successfully performed. Capsular polishing was also performed safely and easily. The posterior capsule remained intact and the intraocular lens was inserted into the bag in all cases. Thus, the use of the 23-gauge illuminated infusion chandelier can improve visualization of the lens structure and capsule, thereby facilitating successful cataract extraction in select patients with vitreous hemorrhage.

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