Arch Ophthalmol
· 2012 Sep · PMID 22965595
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OBJECTIVE: To describe a large family with a novel mutation in CHM. METHODS: Family members were characterized using clinical examination, wide-field fundus photography, wide-field autofluorescence, and spectral domain o...OBJECTIVE: To describe a large family with a novel mutation in CHM. METHODS: Family members were characterized using clinical examination, wide-field fundus photography, wide-field autofluorescence, and spectral domain optical coherence tomography. The CHM mutation was identified with the National Institutes of Health-sponsored eyeGene program. RESULTS: A novel nonsense CHM mutation (T1194G), resulting in a premature stop (Y398X) and loss of the final one-third C-terminal portion of the protein, was identified. A large pedigree was generated from information provided by the twice-married proband. Seven men (aged 27-39 years) and 7 women (aged 22-89 years) were evaluated. Affected men showed characteristic peripheral chorioretinal atrophy with islands of macular sparing. Female carriers exhibited a wide range of variability, from mild pigmentary alterations to significant chorioretinal atrophy with severe vision loss. Older women tended to have a more severe phenotype. Autofluorescence demonstrating subfoveal loss or absence of retinal pigment epithelium correlated with vision loss in both sexes. Spectral domain optical coherence tomography demonstrated dynamic changes and remodeling of the outer retina over time, including focal thickening, drusenlike deposits, and disruption to photoreceptor inner segment and outer segment junctions in young female carriers. CONCLUSIONS: CHM (T1194G) is a novel mutation that manifests a wide range of phenotypic variability in a single family with a trend toward more severe phenotypes in older female carriers. Our findings emphasize the importance of considering X-linked diseases by carefully evaluating pedigrees in women with severe manifestations of disease. CLINICAL RELEVANCE: These findings demonstrate a novel CHM mutation that emphasizes severe posterior pole carrier phenotypes, age-related changes, and early choroideremia disease.
OBJECTIVE: To assess the prevalence and associated risk factors of angle closure in a defined population as part of the Namil Study. METHODS: In this cross-sectional epidemiologic study for residents aged 40 years or old...OBJECTIVE: To assess the prevalence and associated risk factors of angle closure in a defined population as part of the Namil Study. METHODS: In this cross-sectional epidemiologic study for residents aged 40 years or older in Namil-myon, a rural area in central South Korea, the examination included slitlamp biomicroscopy, applanation tonometry, gonioscopy, autorefraction, fundus photography, corneal thickness measurement, visual field test with frequency-doubling technology, and anterior chamber depth (ACD) and axial length (AL) measurements with partial coherence interferometry. Standard automated field test and optical coherence tomography or scanning laser polarimetry were performed to confirm the glaucomatous visual field/optic disc damage. Angle closure included primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG). Definitions of PACS, PAC, and PACG were based on the recommendations from the International Society for Geographical &Epidemiological Ophthalmology. RESULTS: Among the 1426 individuals enrolled for the assessment, with exclusion of cataract surgery, the prevalence rates of PACS, PAC, PACG, and overall angle closure in at least 1 eye were 2.0% (95% CI, 1.3%-2.8%), 0.5% (95% CI, 0.1%-0.9%), 0.7% (95% CI, 0.3%-1.1%), and 3.2% (95% CI, 2.3%-4.2%), respectively. Multivariate analysis found that older age (odds ratio [OR], 1.8797; 95% CI, 1.4624-2.4162), shallower ACD (OR, 0.9982; 95% CI, 0.9977-0.9987), and shorter AL (OR 0.9978; 95% CI, 0.9969-0.9988) (P < .001 for each) were significantly associated with angle closure. CONCLUSIONS: The overall prevalence of angle closure was 3.2% in the present study. On the basis of these findings, increasing age, shallower ACD, and shorter AL appear to be associated with angle closure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00727168.
Gangnon RE, Lee KE, Klein BE
… +3 more, Iyengar SK, Sivakumaran TA, Klein R
Arch Ophthalmol
· 2012 Sep · PMID 22965593
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OBJECTIVES: To investigate the effect of age, sex, and the Y402H variant in the complement factor H (CFH) gene on the incidence, progression, and regression of age-related macular degeneration (AMD) as well as the effect...OBJECTIVES: To investigate the effect of age, sex, and the Y402H variant in the complement factor H (CFH) gene on the incidence, progression, and regression of age-related macular degeneration (AMD) as well as the effect of these factors and AMD on mortality, using multistate models. METHODS: Analyses included 4379 persons aged 43 to 84 years at the time of the census. The status of AMD on a 5-level severity scale was graded from retinal photographs taken at up to 5 study visits between 1988 and 2010. Multistate models in continuous time were used to model the effects of age, sex, and CFH genotype on the incidence, progression, and regression of AMD and mortality. RESULTS: The CFH Y402H genotype CC was associated, relative to genotype TT (reported as hazard ratio; 95% CI), with increased incidence of AMD (no to minimally severe early AMD, 1.98; 1.57-2.49), progression of AMD (minimally severe early to moderately severe early AMD, 1.73; 1.29-2.33; moderately severe early to severe early AMD, 1.30; 0.86-1.94; and severe early to late AMD, 1.72; 1.01-2.91) but not with regression of AMD or mortality. Late AMD was associated with increased mortality (1.37; 1.15-1.62) relative to no AMD, but earlier stages of AMD were not. CONCLUSIONS: Using the multistate models, we show that the Y402H risk variant is associated with lifetime incidence of early AMD and progression of early to late AMD and that late AMD is associated with mortality risk.
OBJECTIVE: To evaluate the effectiveness of low-vision rehabilitation in 2 cohorts derived from the Veterans Affairs Low-Vision Intervention Trial. METHODS: In a prospective study, we observed 44 participants randomly as...OBJECTIVE: To evaluate the effectiveness of low-vision rehabilitation in 2 cohorts derived from the Veterans Affairs Low-Vision Intervention Trial. METHODS: In a prospective study, we observed 44 participants randomly assigned to outpatient low-vision rehabilitation who did not receive additional treatment after the trial ended at 4-month follow-up and 56 participants randomly assigned to the waiting-list control group and thereafter to standard therapy. The outcome measures included visual ability domains (reading, mobility, visual information processing, and visual motor skills) and overall visual ability estimated from difficulty ratings using the 48-item Veterans Affairs Low-Vision Visual Functioning Questionnaire. Mean visual ability scores for the treatment and control groups were compared at baseline, 4 months, and 1 year. A mixed-effects model was used to test treatment effects between groups over time. Differences in visual ability mean scores from baseline to 1 year were compared between the 2 groups. Within-group changes in visual ability were compared from baseline to 1 year, from baseline to 4 months, and from 4 months to 1 year. RESULTS: At baseline, there were no significant differences in mean visual ability scores between groups. From baseline to 4 months, the treatment effects for all visual ability domains and overall visual ability increased to a maximum in the treatment group (P< .001), whereas the mean scores (except visual motor skills) decreased in the control group (P< .01). From 4 months to 1 year, the differences became smaller. There was a loss of visual ability in reading and visual information processing (but not in visual motor skills, mobility, or overall visual ability) in the treatment group and a gain in all visual ability measures in the control group. Interactions of treatment and follow-up time in the mixed models showed the trend of treatment effects significantly changed over time from baseline to 1 year (P< .001) for all visual ability domains and overall visual ability. Both groups demonstrated improvement in visual ability from baseline to 1 year (P< .001) (except for mobility in the control group). Overall visual ability (but not other visual ability domains) improved more in the treatment group than in the control group (P= .01). CONCLUSIONS: Visual ability improved significantly in both groups from baseline to 1 year. The Low-Vision Intervention Trial treatment effect is robust and well maintained for patients with macular diseases.
Bressler SB, Qin H, Beck RW
… +5 more, Chalam KV, Kim JE, Melia M, Wells JA, Diabetic Retinopathy Clinical Research Network
Arch Ophthalmol
· 2012 Sep · PMID 22965591
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OBJECTIVE: To identify factors that predict the success or failure of treatment with intravitreal ranibizumab for patients with diabetic macular edema. METHODS: A total of 37 baseline demographic, systemic, ocular, optic...OBJECTIVE: To identify factors that predict the success or failure of treatment with intravitreal ranibizumab for patients with diabetic macular edema. METHODS: A total of 37 baseline demographic, systemic, ocular, optical coherence tomographic, and fundus photographic variables were assessed for association with change in visual acuity or central subfield thickness between baseline and 1 year in 361 eyes that were randomly assigned to intravitreal ranibizumab with prompt or deferred laser treatment within a trial of ranibizumab, triamcinolone acetonide, and laser treatment for center-involved diabetic macular edema. A categorical variable describing follow-up anatomic responses to therapy was added to the visual acuity outcome model. RESULTS: After adjusting for baseline visual acuity, a larger visual acuity treatment benefit was associated with younger age (P< .001), less severe diabetic retinopathy on clinical examination (P= .003), and absence of surface wrinkling retinopathy (P< .001). The reduction in central subfield thickness during the first treatment year also predicted better visual acuity outcomes (P< .001). After adjusting for baseline central subfield thickness, the presence of hard exudates was associated with more favorable improvement on optical coherence tomographic scan (P= .004). Because only 11 eyes experienced vision loss and 6 eyes experienced an increase in central subfield thickness, factors for poor outcomes could not be evaluated. CONCLUSIONS: A review of baseline factors and anatomic responses during the first year of ranibizumab therapy for association with visual acuity outcome did not identify any features that would preclude ranibizumab treatment. However, baseline central subfield thickness is the strongest predictor of anatomic outcome, and reduction in central subfield thickness during the first treatment year is associated with better visual acuity outcomes.
OBJECTIVE: To evaluate effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity over time in 2 phase 3 clinical trials (RIDE, NCT00473382; RISE, NCT00473330) of ranibizumab for diabetic macular edema. ME...OBJECTIVE: To evaluate effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity over time in 2 phase 3 clinical trials (RIDE, NCT00473382; RISE, NCT00473330) of ranibizumab for diabetic macular edema. METHODS: Participants with diabetic macular edema (n=759) were randomized to monthly sham, 0.3-mg ranibizumab, or 0.5-mg ranibizumab intravitreal injections. Macular laser was available per protocol-specified criteria. Fundus photographs, taken at baseline and periodically, were graded by a central reading center; clinical examinations were performed monthly. The main outcome measures of this report are secondary/exploratory analyses including a 2-step or more and 3-step or more change on the Early Treatment Diabetic Retinopathy Study severity scale in the study eye and a composite DR progression outcome including photographic changes plus clinically important events such as occurrence of vitreous hemorrhage or need for panretinal laser. RESULTS: At 2 years, the percentage of participants with DR progression (worsening by ≥ 2 or ≥ 3 steps) was significantly reduced in ranibizumab-treated eyes compared with sham-treated eyes, and DR regression (improving by ≥ 2 or ≥ 3 steps) was significantly more likely. The cumulative probability of clinical progression of DR as measured by the composite outcome at 2 years was 33.8% of sham-treated eyes compared with 11.2% to 11.5% of ranibizumab-treated eyes. CONCLUSIONS: Intravitreal ranibizumab reduced the risk of DR progression in eyes with diabetic macular edema, and many ranibizumab-treated eyes experienced improvement in DR severity. Because these results are exploratory, the use of intravitreal ranibizumab specifically to reduce DR progression or cause DR regression requires further study.
Grunwald JE, Alexander J, Ying GS
… +17 more, Maguire M, Daniel E, Whittock-Martin R, Parker C, McWilliams K, Lo JC, Go A, Townsend R, Gadegbeku CA, Lash JP, Fink JC, Rahman M, Feldman H, Kusek JW, Xie D, Jaar BG, CRIC Study Group
Arch Ophthalmol
· 2012 Sep · PMID 22965589
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OBJECTIVE: To investigate the association between retinopathy and chronic kidney disease. METHODS: In this observational, cross-sectional study, 2605 patients of the Chronic Renal Insufficiency Cohort (CRIC) study, a mul...OBJECTIVE: To investigate the association between retinopathy and chronic kidney disease. METHODS: In this observational, cross-sectional study, 2605 patients of the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter study of chronic kidney disease, were offered participation. Nonmydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects. The photographs were reviewed in a masked fashion at a central photograph reading center using standard protocols. Presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed by trained graders and a retinal specialist using protocols developed for large epidemiologic studies. Kidney function measurements and information on traditional and nontraditional risk factors for decreased kidney function were obtained from the CRIC study. RESULTS: Greater severity of retinopathy was associated with lower estimated glomerular filtration rate after adjustment for traditional and nontraditional risk factors. The presence of vascular abnormalities usually associated with hypertension was also associated with lower estimated glomerular filtration rate. We found no strong direct relationship between estimated glomerular filtration rate and average arteriolar or venular calibers. CONCLUSIONS: Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and nontraditional risk factors for chronic kidney disease, suggesting that retinovascular pathology reflects renal disease.
Sohn EH, He S, Kim LA
… +6 more, Salehi-Had H, Javaheri M, Spee C, Dustin L, Hinton DR, Eliott D
Arch Ophthalmol
· 2012 Sep · PMID 22965588
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OBJECTIVES To assess the effect of bevacizumab injection on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the ocular fluids of patients with diabetic traction retinal detachment,...OBJECTIVES To assess the effect of bevacizumab injection on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the ocular fluids of patients with diabetic traction retinal detachment, and to determine whether intraoperative and postoperative complications are decreased in eyes given adjunctive preoperative bevacizumab injection. METHODS Twenty eyes of 19 patients were randomized to receive intravitreal bevacizumab or sham injection 3 to 7 days before vitrectomy for severe proliferative diabetic retinopathy. We collected aqueous samples before injection and at the time of vitrectomy and extracted undiluted vitreous samples. RESULTS Five eyes had decreased vascularization of membranes from preinjection to the time of vitrectomy (all in the bevacizumab treatment arm). Median visual acuities were 20/400 in control eyes at baseline and postoperative month 3 (POM3) and 8/200 in the bevacizumab-treated group at baseline and 20/100 at POM3 (P= .30 between control and bevacizumab-treated groups at POM3). All retinas were attached at POM3. Vitreous levels of VEGF were significantly lower in the bevacizumab group than in the control group (P= .03). Vitreous levels of CTGF were slightly lower in the bevacizumab group compared with the control group, but this difference was not statistically significant (P= .38). Levels of CTGF in the aqueous were strongly correlated with CTGF levels in the vitreous of controls (Spearman correlation coefficient, 0.95 [P< .001]). CONCLUSIONS Intravitreal bevacizumab injection reduces vitreous levels of VEGF and produces a clinically observable alteration in diabetic fibrovascular membranes. Ocular fluid levels of CTGF are not significantly affected within the week after VEGF inhibition. Retinal reattachment rates and visual acuity are not significantly altered by preoperative intravitreal bevacizumab injection at POM3. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01270542.
Lee K, Kwon YH, Garvin MK
… +3 more, Niemeijer M, Sonka M, Abràmoff MD
Arch Ophthalmol
· 2012 Sep · PMID 22965586
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OBJECTIVES To test the hypothesis that the amount and distribution of glaucomatous damage along the entire retinal ganglion cell-axonal complex (RGC-AC) can be quantified and to map the RGC-AC connectivity in early glauc...OBJECTIVES To test the hypothesis that the amount and distribution of glaucomatous damage along the entire retinal ganglion cell-axonal complex (RGC-AC) can be quantified and to map the RGC-AC connectivity in early glaucoma using automated image analysis of standard spectral-domain optical coherence tomography. METHODS Spectral-domain optical coherence tomography volumes were obtained from 116 eyes in 58 consecutive patients with glaucoma or suspected glaucoma. Layer and optic nerve head (ONH) analysis was performed; the mean regional retinal ganglion cell layer thickness (68 regions), nerve fiber layer (NFL) thickness (120 regions), and ONH rim area (12 wedge-shaped regions) were determined. Maps of RGC-AC connectivity were created using maximum correlation between regions' ganglion cell layer thickness, NFL thickness, and ONH rim area; for retinal nerve fiber bundle regions, the maximum "thickness correlation paths" were determined. RESULTS The mean (SD) NFL thickness and ganglion cell layer thickness across all macular regions were 22.5 (7.5) μm and 33.9 (8.4) μm, respectively. The mean (SD) rim area across all ONH wedge regions was 0.038 (0.004) mm2. Connectivity maps were obtained successfully and showed typical nerve fiber bundle connectivity of the RGC-AC cell body segment to the initial NFL axonal segment, of the initial to the final RGC-AC NFL axonal segments, of the final RGC-AC NFL axonal to the ONH axonal segment, and of the RGC-AC cell body segment to the ONH axonal segment. CONCLUSIONS In early glaucoma, the amount and distribution of glaucomatous damage along the entire RGC-AC can be quantified and mapped using automated image analysis of standard spectral-domain optical coherence tomography. Our findings should contribute to better detection and improved management of glaucoma.