Early Visual Functional Outcomes and Morphological Responses to Anti-Vascular Growth Factor Therapy in Diabetic Macular Oedema Using Optical Coherence Tomography Angiography.

PURPOSE: Diabetic macular oedema (DME) is a vision-threatening complication of diabetic retinopathy. Spectral domain optical coherence tomography angiography (OCTA) is useful for assessing DME. We performed serial OCTA measurements before and after 3 monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to understand its relationship with best corrected visual acuity (BCVA), central macular thickness (CMT) and vascular indices. METHODS: OCTA assessment consisting of 6 × 6 mm scans centred on fovea and en-face retinal angiograms were obtained. Scans were done at baseline and at 1 month following each of the 3 intravitreal injections of anti-VEGF (ranibizumab, Lucentis®). RESULTS: Our prospective study included 24 eyes of 24 subjects, aged 63.0 ± 5.0 years. There was a mean gain of 0.07 LogMAR (3 letters) and reduction of CMT, vessel density (VD) and perfusion density (PD) by end of 3rd month. CMT was independently associated with improvement in BCVA. There were significant reductions in FAZ area, VD and PD over 3 months from baseline. CONCLUSION: At three months, intravitreal anti-VEGF therapy is associated with visual function recovery in DME, with reduction in CMT being the most reliable predictor of response. OCTA shows a reduction in VD and PD respectively suggestive of reduced macular perfusion in the short term. Simultaneous reduction in FAZ size can be due to reversal of manual displacement of the retinal capillaries resulting from resolution of intraretinal oedema.

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular, but not macrovascular, disease in individuals with and without (pre)diabetes: The Maastricht Study.

AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown. METHODS: Subjects with normal glucose metabolism (n=1796; age: 57.9±8.2 years; 43.3% men), prediabetes (n=478; age: 61.6±7.6 years; 54.0% men) and T2DM (n=669; age: 63.0±7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO. RESULTS: Fasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥30mg/24h [fasting: 1.12 (95% CI: 0.97-1.29); post-OGTT: 1.19 (1.01-1.41)], eGFR<60mL/min/1.73 m2 [fasting: 1.58 (95% CI: 1.38-1.82), post-OGTT: 1.57 (1.34-1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01-2.53), post-OGTT: 1.38 (0.77-2.48)]. No associations with prior CVD were found. CONCLUSION: Fasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.

Need for manual segmentation in optical coherence tomography angiography of neovascular age-related macular degeneration.

PURPOSE: To compare the characteristics of eyes that had manual vs. automated segmentation of choroidal neovascular membrane (CNVM) using optical coherence tomography angiography (OCTA). METHODS: All patients with CNVM underwent OCTA using the Zeiss Angioplex Cirrus 5000. Slabs of the avascular outer retina, outer retina to choriocapillaris (ORCC) region and choriocapillaris were generated. Manual segmentation was done when there were significant segmentation artifacts. Presence of activity of CNVM was adjudged by the presence of subretinal fluid (SRF) on structural OCT and was compared to activity detected on en face OCTA slabs based on well-defined criteria. RESULTS: Eighty-one eyes of 81 patients were recruited of which manual segmentation was required in 46 (57%). Eyes with automated segmentation had significantly more CNVM in the ORCC (75%) whereas those with manual segmentation had deeper CNVM (sub-RPE = 22%, intra-PED = 22%) (p<0.001). Twenty eyes (25%) were found to have active CNVM on both the structural OCT and OCTA while an additional 19 eyes were presumed to have active CNVM on OCTA alone. There was only modest concordance between disease activity detected using structural OCT and OCTA (Kappa = 0.47, 95% CI = 0.30 to 0.64). CONCLUSIONS: Manual segmentation of OCTA is required in more than 50% eyes with CNVM and this progressively increases with increasing depth of CNVM location from the ORCC to below the RPE. There is moderate concordance between OCTA and structural OCT in determining CNVM activity.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. INTRODUCTION: To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. METHODS: Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. RESULTS: After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (- 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%), cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. CONCLUSIONS: In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.

Adaptive optics imaging of the outer retinal tubules in Bietti's crystalline dystrophy.

PurposeTo study the outer retinal tubules using spectral domain optical coherence tomography and adaptive optics and in patients with Bietti's crystalline dystrophy.MethodsTen eyes of five subjects from five independent families with Bietti's crystalline Dystrophy (BCD) were characterized with best-corrected visual acuity (BCVA), full-field electroretinography, and fundus autofluorescence (FAF). High-resolution images were obtained with the spectral domain optical coherence tomography (SD-OCT) and adaptive optics (AO).ResultsSD-OCT showed prominent outer retinal layer loss and outer retinal tubulations at the margin of outer retinal loss. AO images displayed prominent macrotubules and microtubules with characteristic features in eight out of the 10 eyes. Crystals were present in all ten eyes. There was a reduction in the cone count in all eyes in the area outside the outer retinal tubules (ORT).ConclusionsThis study describes the morphology of the outer retinal tubules when imaged enface on the adaptive optics in patients with BCD. These findings provide insight into the macular structure of these patients. This may have prognostic implications and refine the study on the pathogenesis of BCD.

Correlation of structure and function of the macula in patients with retinitis pigmentosa.

PURPOSE: To correlate the structure of the macula, as measured by spectral-domain optical coherence tomography (SD-OCT) and function, as measured by microperimetry (MAIA) in patients with retinitis pigmentosa (RP) and relatively good visual acuity. DESIGN: Prospective, cross-sectional, non-intervention study. SUBJECTS: Patients with RP. METHODS: Thirty patients with RP and good central visual acuity were identified. Each patient underwent SD-OCT of the macula and microperimetry. The images were overlaid using the custom-designed software. The retinal sensitivity by microperimetry was correlated with corresponding retinal thickness, as measured by the SD-OCT. ELM, COST, and IS/OS junction were scored as intact, disrupted, or absent. MAIN OUTCOME MEASURES: Comparing the retinal sensitivity on the MAIA with various measurements on the SD-OCT. RESULTS: The retinal sensitivity on the MAIA showed a significant correlation with total retinal thickness and outer retinal thickness on the SD-OCT. There was no association with either the inner retinal thickness or the choroidal thickness. ORT showed a statistically significant correlation with the anatomical classification of ELM (r=-0.76, P<0.001), IS/OS (r=-0.800, P<0.001), and COST (r=-0.733, P<0.001). CONCLUSION: This study determined that there was a high correlation of the structure and function of the central macula in patients with RP. These studies are important to establish surrogate markers that can be used as end points for various tests in future therapeutic clinical trials.

Macular pigment optical density measurements: evaluation of a device using heterochromatic flicker photometry.

PURPOSE: Accurate assessment of the amount of macular pigment (MPOD) is necessary to investigate the role of carotenoids and their assumed protective functions. High repeatability and reliability are important to monitor patients in studies investigating the influence of diet and supplements on MPOD. We evaluated the Macuscope (Macuvision Europe Ltd., Lapworth, Solihull, UK), a recently introduced device for measuring MPOD using the technique of heterochromatic flicker photometry (HFP). We determined agreement with another HFP device (QuantifEye; MPS 9000 series: Tinsley Precision Instruments Ltd., Croydon, Essex, UK) and a fundus reflectance method. METHODS: The right eyes of 23 healthy subjects (mean age 33.9 ± 15.1 years) were measured. We determined agreement with QuantifEye and correlation with a fundus reflectance method. Repeatability of QuantifEye was assessed in 20 other healthy subjects (mean age 32.1 ± 7.3 years). Repeatability was also compared with measurements by a fundus reflectance method in 10 subjects. RESULTS: We found low agreement between test and retest measurements with Macuscope. The average difference and the limits of agreement were -0.041 ± 0.32. We found high agreement between test and retest measurements of QuantifEye (-0.02 ± 0.18) and the fundus reflectance method (-0.04 ± 0.18). MPOD data obtained by Macuscope and QuantifEye showed poor agreement: -0.017 ± 0.44. For Macuscope and the fundus reflectance method, the correlation coefficient was r = 0.05 (P = 0.83). A significant correlation of r = 0.87 (P<0.001) was found between QuantifEye and the fundus reflectance method. CONCLUSIONS: Because repeatability of Macuscope measurements was low (ie, wide limits of agreement) and MPOD values correlated poorly with the fundus reflectance method, and agreed poorly with QuantifEye, the tested Macuscope protocol seems less suitable for studying MPOD.

Evaluation of the Lenstar LS 900 non-contact biometer.

BACKGROUND/AIMS: Evaluation of the reproducibility of the Lenstar LS 900 non-contact biometer, and a comparison with the Visante anterior-segment optical coherence tomography (AS-OCT) and the IOLMaster. METHODS: Central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), keratometry (K) values, corneal diameter (CD) and axial length (AL) were obtained in 38 healthy volunteers (76 eyes) to determine the reproducibility of the Lenstar. CCT, ACD, CD, K values and AL measurements measured with the Lenstar were compared with the AS-OCT and IOLMaster. Intraocular lens (IOL) power calculations were done to study the significance of the difference between AL measurements. RESULTS: The reproducibility of the Lenstar was better than 0.9% for CCT, ACD, LT, K values and AL measurements. Although all correlations were highly significant (p<0.001), all comparisons showed a significant difference, except for the comparison of CD measurements using the Lenstar and IOLMaster (p = 0.175). The differences in IOL power calculations for an AL of 20, 25 and 30 mm with a mean difference between Lenstar and IOLMaster AL measurements of 0.03 mm, were 0.13 D, 0.10 D and 0.08 D, respectively. CONCLUSION: The reproducibility of the Lenstar was excellent. Small but significant differences exist between the Lenstar, Visante OCT and the IOLMaster. Therefore, measurements of the Lenstar, AS-OCT and IOLMaster are not interchangeable. Despite the significant difference between AL measurements, there is no clinically significant difference in the IOL power calculation results.

Patient ignorance is the main reason for treatment delay in primary rhegmatogenous retinal detachment in The Netherlands.

AIMS: Treatment delay of progressive vision-threatening conditions should be minimal. In this study, the treatment delay of patients with a rhegmatogenous retinal detachment (RRD) undergoing retinal detachment surgery was quantified, and causes for this delay were evaluated. MATERIALS AND METHODS: Consecutive patients (n=205) presenting with a primary RRD between June 2006 and June 2007 at the tertiary referral center (TRC) were interviewed. Five categories of delay were discerned in the following: 'patient delay,' 'general practitioner's delay,' 'referring ophthalmologist's delay,' 'delay at the TRC' and 'delay before surgery at the TRC'. In addition, overall delay was calculated. RESULTS: In total, 186 eyes were included in the analysis. Median overall delay between the patients' first symptoms and RRD surgery was 10 days. Almost 60% of this overall delay time was due to patient delay and the delay of the general practitioner. More than 50% of patients had a delay owing to unawareness of the symptoms. The median patient delay was significantly lower in patients with a vitreous hemorrhage and in patients with a history of a RRD in the fellow eye. CONCLUSIONS: The major reason for patient delay with a RDD was the patients' unawareness and unfamiliarity with the symptoms of a retinal detachment.

Analysis of visual pigment by fundus autofluorescence.

This study investigated changes of short-wavelength fundus autofluorescence (SW-AF) by retinal bleaching effects. All measurements were performed with the Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done on a healthy eye after dark adaptation. Photopigment was bleached within the central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of this region was performed, and SW-AF of the surrounding, unbleached 25 degrees fundus region was subsequently studied by a wide-field lens. Next, another 30 degrees SW-AF image of the posterior pole was obtained after complete dark adaptation. Then an extra SW-AF examination was performed with 15 degrees temporal eccentricity, overlapping the original examination area. Finally, a successive image series was carried out on the dark-adapted eye to test for bleaching kinetics. The second and third experiments were also performed on eyes with macular dystrophies. Distinct regions of increased SW-AF were observed after strong illumination with the blue excitation light in all eyes studied. During light adaptation mean gray levels showed a saturation plateau after an initial steep increase. The resulting gray-value maps showed significant differences of pixel intensities between bleached and unbleached parts of the fundus. Two-dimensional density difference maps allowed analysis of visual pigment distribution and density in both healthy eyes and eyes with macular dystrophies. Our observations highlight the viability of objective, non-invasive evaluation of visual pigment in the healthy and diseased human retina by means of confocal fundus autofluorescence.

Risk factors for redetachment and worse visual outcome after silicone oil removal in eyes with complicated retinal detachment.

PURPOSE: The goal of this study was to identify risk factors for redetachment and/or a worse visual outcome after silicone oil removal (SOR) for complicated retinal detachment. METHODS: The authors retrospectively analyzed 287 consecutive eyes with SOR between January 1999 and December 2003. RESULTS: Anatomic success after SOR was achieved in 81% of the eyes. The overall anatomic success at the end of follow-up was 94%. Postoperative ocular hypertension was found in 8% of the eyes, hypotony in 6% of the eyes, and keratopathy in 29% of the eyes. After SOR 43% of the eyes had an improvement in visual acuity of at least two Snellen lines. After multivariate analysis, male sex, the presence of preoperative rubeosis, and proliferative diabetic retinopathy (PDR) were found to be risk factors for recurrent retinal detachment. Male sex, preoperative visual acuity of <0.1 Snellen lines, PDR, the performance of three more operations, any size of retinectomy, and hypotony were found to be associated with a poor visual outcome of Snellen visual acuity <0.1. CONCLUSIONS: Retinal detachment after SOR in the current unselected series of eyes occurred in approximately 20%, which is comparable to the Silicone Oil Study reports, published approximately 20 years ago. However, preoperative selection was then made, and less than 50% of the silicone oil-filled eyes had SOR. The higher overall anatomic success in the current study may be due to improved vitreoretinal surgical techniques.

[Lacrimal duct probing in young children with a congenital lacrimal duct obstruction at the Utrecht University Medical Center: generally an effective treatment]. / Traanwegsondage bij jonge kinderen met een aangeboren traanwegobstructie in het Universitair Medisch Centrum Utrecht: doorgaans een effectieve behandeling.

OBJECTIVE: To assess the results of lacrimal duct probing in young children with epiphora, due to a congenital nasolacrimal duct obstruction. DESIGN: Retrospective, descriptive. METHOD: Data were collected from medical dossiers on the results of lacrimal duct probing in children (0-48 months) with epiphora that was done in the period from January 1, 1997 to December 31, 2001 at the University Medical Centre in Utrecht, the Netherlands. The percentage of eyes that showed complete resolution of symptoms three months after the final probing was calculated. RESULTS: Of the 89 children who had undergone lacrimal duct probing, seven were excluded and in three children (six eyes) the data could not be retrieved. In 96 of the remaining 116 eyes (83%), the symptoms disappeared: this included 96% of the age group 0-12 months (n = 25), 85% of the 13-24 months-olds (n = 55), 77% of the 25-36 months-olds (n = 22) and 57% of the 37-48 months-olds (n = 14). No complications of probing were seen. CONCLUSION: In most children in the various age groups, epiphora disappeared. Thus, children do not need to be probed in the first year of life out of fear of failure at an older age. Whether or not probing shortens the duration of epiphora cannot be determined on the basis of either this study or the literature.

Comparison of fluorescence of sodium fluorescein in retinal angiography with measurements in vitro.

To quantify dye leakage in ocular fluorescein angiography, the arterial concentration of sodium fluorescein has to be determined. We investigated whether the nonlinear relationship between the fluorescein concentration and the fluorescence intensity obtained by in vitro measurements corresponds with that measured in vivo in a retinal artery. The time series of fluorescence in a retinal artery were recorded using an in-house-designed and -built confocal scanning laser ophthalmoscope in 11 healthy volunteers. Three different doses of sodium fluorescein were injected successively. About 10 min after the last injection a venous blood sample was drawn. The three in vivo peak intensities were fitted by least squares on the in vitro calibration curve using the first peak concentration and an intensity scaling factor as the two unknown parameters. The fit showed that the saturation of the three in vivo peak intensities corresponded well with the in vitro data. Calculation of the intensity scaling factor from the blood sampling data confirmed the result of the fit. The fitted concentration was verified by showing that the cardiac output necessary to obtain this concentration was within the physiological range. The fluorescence measured in our in vitro experimental setup corresponded well with the in vivo measurements. Therefore, the results from in vitro measurements can be applied in the analysis of fluorescein angiograms.