Matthias Bolz

Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema.

PURPOSE To analyze hyperreflective foci typically seen in diabetic macular edema (DME) in optical coherence tomography (OCT). DESIGN Prospective clinical trial. PARTICIPANTS Twelve consecutive patients with treatment-naïve, clinically significant DME. METHODS During a same-day examination, a standardized visual acuity assessment (Early Treatment of Diabetic Retinopathy Study protocol), infrared fundus imaging, color fundus photography, and biomicroscopy were performed. Additionally, all patients were scanned using Stratus, Cirrus, and Spectralis OCT and results correlated. MAIN OUTCOME MEASURES Morphologic changes secondary to DME. RESULTS In all eyes with DME, distinct hyperreflective foci distributed throughout all retinal layers were found in the OCT scans of all 3 OCT devices. These deposits could not be identified by infrared imaging, fundus photography, or biomicroscopy as long as they were not confluent. Accumulations of such foci at the border of the outer nuclear and in the outer plexiform layer were recognizable clinically as hard exudates showing the same hyperreflective features in OCT. The hyperreflectivity of these foci did not correspond with intraretinal hemorrhage, nor did the lesions cause the characteristic OCT laser beam scattering phenomena typically seen secondary to intraretinal bleedings or microaneurysms. Further, they were detected within the walls of intraretinal microaneurysms. CONCLUSIONS Well-demarcated, hyperreflective foci were identified in the retina of patients with DME. The deposits were located within walls of intraretinal microaneurysms and scattered throughout all retinal layers, forming confluent plaques in the outer plexiform layer. It is suggested that the foci represent extravasated lipoproteins and/or proteins being a very early subclinical barrier breakdown sign in DME.

Angiogenic and inflammatory markers in the intraocular fluid of eyes with diabetic macular edema and influence of therapy with bevacizumab.

Purpose: The purpose of this study was to determine the concentrations of angiogenic and inflammatory markers in human eyes with diffuse diabetic macular edema before and during therapy with intravitreal bevacizumab and their association with disease activity. Methods: In a prospective clinical trial, 10 eyes of 10 consecutive patients with vision loss because of diabetic macular edema were compared with 10 eyes of 10 age-matched controls. Bevacizumab was administered at baseline; retreatments were given monthly according to disease activity. During a follow-up of 6 months, aqueous humor samples were taken each time intravitreal therapy was administered. A multiplex assay was used for measurement of 12 different growth factors and cytokines. Results: Aqueous humor of eyes with diabetic macular edema demonstrated a significantly increased expression of monocyte chemoattractant protein-1 and interleukin-8 and higher, but not significant, levels of interleukin-6 and vascular endothelial growth factor. Intravitreal therapy with bevacizumab resulted in a significant decrease of vascular endothelial growth factor below physiologic levels. This change was not associated with clinical disease activity as measured by visual acuity and central retinal thickness. Conclusion: Eyes with diabetic macular edema showed a different profile of monocyte chemoattractant protein-1 and interleukin-8 as compared with controls. The intraocular vascular endothelial growth factor expression decreased significantly after the first intravitreal injection of bevacizumab; this reduction was prolonged by consecutive monthly retreatment.

A Systematic Correlation between Morphology and Functional Alterations in Diabetic Macular Edema

PURPOSE The aim of this study was to correlate different types of retinal morphologic alterations secondary to diabetic macular disease with their characteristic impact on retinal function. METHODS In the present cross-sectional study, 26 eyes of 26 diabetic patients with clinically significant macular edema were examined. All patients underwent complete standardized ophthalmologic examination, including SD-OCT and microperimetry. Microperimetric values were projected over the scanning laser ophthalmoscope image of the OCT device, allowing direct correlation of functional and morphologic parameters. Results over all 1066 individual areas were analyzed using a general linear model. RESULTS All the characteristic morphologic alterations demonstrated a significant effect on retinal function (P < 0.0002), except for outer nuclear layer (ONL) hyporeflectivity and small ONL cysts. Large ONL cysts (>220 μm) and serous retinal detachment had the greatest estimated negative effect on retinal sensitivity (-3.86 and -3.66 dB), followed by medium-sized ONL cysts, hard exudates associated with an extinction of the scan signal, and inner nuclear layer cysts. CONCLUSIONS In diabetic macular edema, serous retinal detachment and large ONL cysts are the two morphologic changes with the greatest negative impact on retinal function.

A Systematic Correlation of Angiography and High-Resolution Optical Coherence Tomography in Diabetic Macular Edema

PURPOSE To correlate leakage patterns in fluorescein angiography (FA) images and retinal morphologic features in high-definition optical coherence tomography (HD OCT) images in diabetic macular edema. DESIGN Prospective pilot study and case series. PARTICIPANTS Nine consecutive patients (10 eyes) with diabetic macular edema. METHODS All patients were examined using FA (HRA 2; Heidelberg Engineering) and HD OCT (Carl Zeiss Meditec; resolution, 512x128 pixels, 5.8x5.8 mm, and high-resolution scans consisting of 4096 A scans) on the same day. Using Adobe Photoshop (CS2 Version 9.0; Adobe Systems Incorporated, San Jose, CA) a grid containing 15x7 fields was superimposed on the HD OCT en face image and a late-phase FA image according to retinal landmarks. In each patient, a standardized analysis of 105 subfields was performed to provide a characterization of the type of vascular leakage in FA and the associated retinal morphologic changes in corresponding locations. MAIN OUTCOME MEASURES Angiographic leakage type and structural alteration in retinal morphologic features in OCT. RESULTS There was a high consistency between FA and OCT in the petaloid pattern of hyperfluorescence that correlated with the presence of large cystic spaces in the outer nuclear layer (ONL) and the outer plexiform layer (OPL) with or without subretinal fluid in 30.4% and 69.6% of graded fields, respectively. A honeycomblike pattern of hyperfluorescence was associated with swelling and cystic spaces in ONL, OPL, the inner nuclear, and the inner plexiform layer in 71.4% of graded fields. Diffuse patterns of hyperfluorescence did not correlate with characteristic retinal changes in HD OCT, but rather showed diversity in the type of morphologic alteration. The presence of central fluid pooling, such as subretinal fluid, could be identified only by HD OCT and not by FA. CONCLUSIONS In the examined patients, a petaloid pattern and a honeycomb pattern of hyperfluorescence observed in FA were found to correlate to characteristic changes in HD OCT, whereas a diffuse leakage pattern was associated with nonuniform changes in retinal morphologic features. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Linear relationship of refractive and biometric lenticular changes during accommodation in emmetropic and myopic eyes.

Aim: Aim of this study was to investigate the relationship between refractive changes in the eye and biometric changes of the human crystalline lens during accommodation. Furthermore, differences in these relationships between young, healthy emmetropic and myopic subjects were analyzed. Methods: Mean relative change in anterior chamber depth (ACD), lens thickness (LT), anterior segment length (ASL  =  ACD + LT) and in objective refraction were simultaneously assessed during near-point-induced accommodation in 10 emmetropic and 10 myopic subjects. Via a beam splitter, measurements were performed simultaneously using partial coherence interferometry (PCI) and infrared (IR) photorefraction. Results: On average, for each diopter of accommodation LT increased by 0.063 mm in emmetropic and by 0.072 mm in myopic eyes, and ACD decreased by 0.047 mm and 0.057 mm, respectively. Mean ASL, indicating the position of the posterior lens pole, increased by 0.009 mm in emmetropic and by 0.013 mm in myopic eyes. The correlation between refractive and biometric changes was found to be essentially linear in both subgroups. Differences in ACD between emmetropic and myopic eyes were statistically significant at an accommodative stimulus of –1 D (p<0.04) and –2 D (p<0.02). Conclusion: The biometric and refractive changes of the human lens are highly correlated and linear in function in both emmetropic and myopic eyes.

Advantage of three dimensional animated teaching over traditional surgical videos for teaching ophthalmic surgery: a randomised study

Background/aim: Owing to the complex topographical aspects of ophthalmic surgery, teaching with conventional surgical videos has led to a poor understanding among medical students. A novel multimedia three dimensional (3D) computer animated program, called “Ophthalmic Operation Vienna” has been developed, where surgical videos are accompanied by 3D animated sequences of all surgical steps for five operations. The aim of the study was to assess the effect of 3D animations on the understanding of cataract and glaucoma surgery among medical students. Method: Set in the Medical University of Vienna, Department of Ophthalmology, 172 students were randomised into two groups: a 3D group (n = 90), that saw the 3D animations and video sequences, and a control group (n = 82), that saw only the surgical videos. The narrated text was identical for both groups. After the presentation, students were questioned and tested using multiple choice questions. Results: Students in the 3D group found the interactive multimedia teaching methods to be a valuable supplement to the conventional surgical videos. The 3D group outperformed the control group not only in topographical understanding by 16% (p<0.0001), but also in theoretical understanding by 7% (p<0.003). Women in the 3D group gained most by 19% over the control group (p<0.0001). Conclusions: The use of 3D animations lead to a better understanding of difficult surgical topics among medical students, especially for female users. Gender related benefits of using multimedia should be further explored.

In Vivo Retinal Morphology after Grid Laser Treatment in Diabetic Macular Edema

PURPOSE To analyze immediate in vivo intraretinal morphologic changes secondary to standardized grid photocoagulation using spectral domain optical coherence tomography (SD OCT). DESIGN Prospective clinical trial. PARTICIPANTS Thirteen consecutive patients with treatment-naïve clinically significant diabetic macular edema (DME). METHODS Before and 1 day after standardized grid photocoagulation using the PASCAL system (Pattern Scan Laser, OptiMedica Corporation, Santa Clara, CA), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) examinations based on an eye-tracking system, infrared fundus imaging, color fundus photography, and biomicroscopy were performed. A standardized visual acuity assessment (Early Treatment Diabetic Retinopathy Study protocol) and fluorescein angiography were performed at baseline. MAIN OUTCOME MEASURES Morphologic changes secondary to grid laser treatment. RESULTS One day after laser therapy, immediate morphologic alterations of only the outer retinal layers, that is, the retinal pigment epithelium (RPE), the photoreceptor layer (PRL), and the outer nuclear layer (ONL), were observed. The shape of the laser-induced lesions did not show a sagittal alteration pattern throughout all 3 of the layers, however, but rather seemed to follow an oblique pathway throughout the ONL, changing direction at the level of the external limiting membrane and proceeding sagittally through the PRL and RPE. These morphologic changes also induced biometric changes, such as a decrease in central retinal thickness combined with local thickening at the lesion site, especially in the PRL. CONCLUSIONS Spectral domain optical coherence tomography provides new insight into the immediate morphologic changes after laser treatment using the PASCAL laser system. Standardized grid photocoagulation induces characteristic homogenous alteration in the neurosensoric retinal layers. Biometric changes, indicating an immediate effect, were observed within 1 day after treatment.

Effect of anterior capsule polishing on the posterior capsule opacification-inhibiting properties of a sharp-edged, 3-piece, silicone intraocular lens: three- and 5-year results of a randomized trial.

PURPOSE: To evaluate the long‐term effects of anterior capsule polishing on regeneratory posterior capsule opacification (PCO), anterior capsule opacification (ACO), and fibrotic PCO with a silicone intraocular lens (IOL) with sharp optic edges. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: This prospective bilateral randomized patient‐ and examiner‐masked clinical trial comprised 130 eyes of 65 patients with bilateral age‐related cataract. All eyes had implantation of a 3‐piece silicone IOL with a truncated, sharp‐edged optic (CeeOn Edge 911A, Advanced Medical Optics). In 1 eye, the anterior capsule was extensively polished using an aspiration curette after phacoemulsification and cortex aspiration. Regenerative PCO was quantified objectively, while ACO and fibrotic PCO were graded subjectively 1, 2, 3, and 5 years postoperatively. RESULTS: The mean ACO score was significantly lower in the eyes in which the anterior capsule had been polished (1 year, P<.02; 2 years, P<.03; 3 years, P<.01; 5 years, P<.01). The mean difference in regeneratory PCO and fibrotic PCO scores between the 2 groups was not statistically significant. CONCLUSIONS: Three years after cataract surgery, eyes in which the anterior capsule had been polished had significantly less ACO. However, polishing did not lower PCO intensity when a sharp‐edged CeeOn 911A IOL was implanted in the bag. Although results indicate that anterior capsule polishing may enhance the development of regeneratory PCO, this trend did not reach statistical significance.

Morphological and functional analysis of the loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration

Aim To quantify and correlate the morphological and functional effects of the recommended loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration (AMD). Methods In a prospective, interventional clinical trial, 29 consecutive patients (29 eyes) with choroidal neovascularisation secondary to AMD received three initial monthly intravitreal injections of ranibizumab. During this loading regimen, best corrected visual acuity (BCVA) and microperimetry (MP) testing, as well as optical coherence tomography and fluorescein angiography (FA), were performed using a standardised protocol and the results correlated. Results Significant morphological and functional therapeutic effects were observed as early as 1 week following the first treatment. Throughout the loading-dose period, central retinal thickness, including intraretinal cysts and subretinal fluid, decreased fast and significantly (p<0.01); pigment epithelial detachment resolved less rapidly. The mean leakage area by FA decreased (p<0.01) and retinal function (BCVA and MP) increased significantly (both p<0.01). However, the change in morphology and function was only significant between baseline and week 1. There was no significant additional morphological or functional benefit following the second and third injection. Conclusion The initial administration of intravitreal ranibizumab in neovascular AMD induced a significant effect on intra- and subretinal fluid and visual function; subsequent injections had a less pronounced effect. It remains to be determined whether this loading regimen should be mandatory in all patients or if a single dose regimen would lead to a comparable functional and morphological retinal improvement.

Repeated intravitreal bevacizumab (Avastin®) treatment of persistent new vessels in proliferative diabetic retinopathy after complete panretinal photocoagulation

Acta Ophthalmol. 2011: 89: 76–81