3-year-data of combined navigated laser photocoagulation (Navilas) and intravitreal ranibizumab compared to ranibizumab monotherapy in DME patients.

PURPOSE: The prospective, comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema has shown advantage of a combination therapy compared to ranibizumab monotherapy at year 1 with significantly reduced injections. The purpose of this retrospective study was to determine the long-term visual gains and need of injections in a 3 year-follow-up period. METHODS: Retrospective analysis of patients of the original study in the long-term follow-up from month 12 to 36. BCVA measurements following the original 1 year study were taken using logMAR charts. Injections were provided with standard of care using PRN, based on change in BCVA and CRT using SD-OCT scans. Main outcome measures were change in BCVA and mean number of injections from 12 to 36 months. RESULTS: BCVA was stable in both groups from 12 through 36 months, showing a change of 0.16 ± 0.1 log MAR. Following the initial reduction in required injections at month 12, combination therapy patients continued to require 1.3 times fewer injections over the next 24 months (2.91 ± 2.3 vs 3.85±3.7 injections for monotherapy). CONCLUSIONS: Combination of navigated laser and ranibizumab achieved BCVA gains equivalent to anti-VEGF monotherapy. These results could be maintained through month 36. Required injections were 2.0 injections lower in year 1 and further 1.3 times fewer in year 2 and 3 in the combination group compared to monotherapy. Adding navigated laser photocoagulation to intravitreal anti-VEGF therapy may still represent a superior therapeutic approach to DME patients.

Odorant Receptor 51E2 Agonist ß-ionone Regulates RPE Cell Migration and Proliferation.

The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand ß-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.

Anti-VEGF treatment and peripheral retinal nonperfusion in patients with central retinal vein occlusion.

PURPOSE: To evaluate the association between the size of peripheral retinal nonperfusion and the number of intravitreal ranibizumab injections in patients with treatment-naïve central retinal vein occlusion (CRVO). METHODS: Fifty-four patients with treatment-naïve CRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography imaging and ultrawide-field fluorescein angiography. Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmologic Society. Two ophthalmologists quantified the areas of peripheral retinal nonperfusion (group 1= less than five disc areas, group 2= more than five disc areas). Correlation analyses between the size of nonperfusion with best-corrected visual acuity, central subfield thickness, and the number of intravitreal injections were performed. RESULTS: Best-corrected visual acuity improved significantly after intravitreal injections (P<0.001, both groups). Final central subfield thickness after treatment did not significantly differ between both groups (P=0.92, P=0.96, respectively). Mean number of injections in group 1 and group 2 was 4.12±2.73 and 9.32±3.84, respectively (P<0.001). There was a significant positive correlation between areas of nonperfusion and the number of injections in each group. (R=0.97, P<0.001; R=0.94, P<0.001, respectively). CONCLUSION: Peripheral retinal nonperfusion in patients with CRVO correlates significantly with the number of needed intravitreal ranibizumab injections. Ultrawide-field fluorescein angiography is a useful tool for detection of peripheral retinal ischemia, which may have direct implications in the diagnosis, follow-up, and treatment of these patients.

Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion.

AIM: To evaluate the association between the size of peripheral retinal non-perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema. METHODS: A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion. RESULTS: Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23±16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23±15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387±115 µm to 321±115 µm (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61±1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001). CONCLUSION: Peripheral retinal non-perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema.

Evaluation of the New "SAVE" Protocol in Diabetic Macular Edema Over the Course of Anti-VEGF Treatment.

BACKGROUND: To evaluate a recently established grading protocol for diabetic macular edema (DME) over the course of intravitreal anti-VEGF treatment with ranibizumab. METHODS: Fluorescein angiography images and optical coherence tomography scans before treatment and after 3 monthly applied intravitreal ranibizumab injections were retrospectively graded for each included study eye according to the recently introduced "SAVE" grading protocol ("S"= subretinal fluid; "A"= "area of retinal thickening"; "V"="vitreo-retinal abnormalities"; "E"="etiology of leakage focal versus non-focal") and correlated with best-corrected visual acuity (BCVA) in letters (lett). RESULTS: Five of the 39 included study eyes had subretinal fluid ("S") before treatment which resolved during treatment. BCVA of study eyes with an initial retinal thickening smaller than one disc diameter ("A") was non-significantly higher compared to patients with a retinal thickening greater than one disc diameter (34.0 ± 17.9 lett versus 25.3 ± 13.3 lett, p=0.236) but became significant during treatment (40.5 ± 10.0 lett versus 28.3 ± 13.1 lett, p=0.004). No difference in BCVA was observed between patients with or without vitreo-retinal abnormalities ("V") before and during therapy. BCVA in patients with focal leakage ("E") was significantly higher than in patients with non-focal leakage before (33.1 ± 12.3 lett versus 23.3 ± 13.3 lett, p=0.017) and during (38.9 ± 10.9 lett versus 26.3 ± 12.6 lett, p=0.002) therapy. CONCLUSIONS: Applying the grading protocol "SAVE", focal leakage ("E") was the only retrospectively observed parameter which significantly correlated with a better BCVA before therapy and over the course of treatment in patients with fovea-involving DME.

Wide-Field Megahertz OCT Imaging of Patients with Diabetic Retinopathy.

PURPOSE: To evaluate the feasibility of wide-field Megahertz (MHz) OCT imaging in patients with diabetic retinopathy. METHODS: A consecutive series of 15 eyes of 15 patients with diagnosed diabetic retinopathy were included. All patients underwent Megahertz OCT imaging, a close clinical examination, slit lamp biomicroscopy, and funduscopic evaluation. To acquire densely sampled, wide-field volumetric datasets, an ophthalmic 1050 nm OCT prototype system based on a Fourier-domain mode-locked (FDML) laser source with 1.68 MHz A-scan rate was employed. RESULTS. We were able to obtain OCT volume scans from all included 15 patients. Acquisition time was 1.8 seconds. Obtained volume datasets consisted of 2088 × 1044 A-scans of 60° of view. Thus, reconstructed en face images had a resolution of 34.8 pixels per degree in x-axis and 17.4 pixels per degree. Due to the densely sampled OCT volume dataset, postprocessed customized cross-sectional B-frames through pathologic changes such as an individual microaneurysm or a retinal neovascularization could be imaged. CONCLUSIONS: Wide-field Megahertz OCT is feasible to successfully image patients with diabetic retinopathy at high scanning rates and a wide angle of view, providing information in all three axes. The Megahertz OCT is a useful tool to screen diabetic patients for diabetic retinopathy.

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio.

PURPOSE: Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress. METHODS: ARPE-19 cells were treated with 1-100 µM idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono- and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated ß-galactosidase (SA-ß-Gal) activity were investigated under exposure to hydrogen peroxide (H2O2). RESULTS: Idebenone concentrations from 1 to 20 µM showed no toxic effects on ARPE-19 cells. When cells were treated with H2O2, pretreatment with 5, 7.5, 10, and 20 µM idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-ß-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H2O2. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H2O2-induced apoptosis, not necrosis. CONCLUSION: In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio.

Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema.

OBJECTIVE: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME). RESEARCH DESIGN AND METHODS: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12. RESULTS: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001). CONCLUSIONS: Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.

Role of wide-field autofluorescence imaging and scanning laser ophthalmoscopy in differentiation of choroidal pigmented lesions.

AIM: To evaluate the diagnostic properties of wide-field fundus autofluorescence (FAF) scanning laser ophthalmoscope (SLO) imaging for differentiating choroidal pigmented lesions. METHODS: A consecutive series of 139 patients were included, 101 had established choroidal melanoma with 13 untreated lesions and 98 treated with radiotherapy. Thirty-eight had choroidal nevi. All patients underwent a full ophthalmological examination, undilated wide-field imaging, FAF and standardized US examination. FAF images and imaging characteristics from SLO were correlated with the structural findings in the two patient groups. RESULTS: Mean FAF intensity of melanomas was significantly lower than the FAF of choroidal nevi. Only 1 out of 38 included eyes with nevi touched the optic disc compared to 31 out of 101 eyes with melanomas. In 18 out of 101 melanomas subretinal fluid was seen at the pigmented lesion compared to none seen in eyes with confirmed choroidal nevi. In "green laser separation", a trend towards more mixed FAF appearance of melanomas compared to nevi was observed. The mean maximal and minimal transverse and longitudinal diameters of melanomas were significantly higher than those of nevi. CONCLUSION: Wide-field SLO and FAF imaging may be an appropriate non-invasive diagnostic screening tool to differentiate benign from malign pigmented choroidal lesions.

Assessment of ß-zone peripapillary atrophy by optical coherence tomography and scanning laser ophthalmoscopy imaging in glaucoma patients.

PURPOSE: To assess ß-zone peripapillary atrophy (ß-PPA) using spectral domain optical coherence tomography (SD-OCT), scanning laser ophthalmoscopy (SLO), and fundus auto-fluorescence (FAF) imaging in patients with primary open-angle glaucoma with advanced glaucomatous visual field defects. METHODS: A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma were included in this study. All study participants underwent a full ophthalmic examination followed by SD-OCT, wide-field SLO, and FAF imaging of the optic nerve head and the peripapillary region. RESULTS: Eighty-four glaucomatous eyes were included in our prospective study. Correlation analyses for horizontally and vertically obtained ß-PPA for all three imaging modalities (color SLO, FAF, and SD-OCT) revealed highest correlations between FAF and color SLO (Pearson correlation coefficient: 0.904 [P<0.001] for horizontal ß-PPA and 0.786 [P<0.001] for vertical ß-PPA). Bland-Altman plotting revealed highest agreements between color SLO and FAF, with -2.1 pixels ±1.96 standard deviation (SD) for horizontal ß-PPA, SD: 10.5 pixels and 2.4 pixels ±1.96 SD for vertical ß-PPA. CONCLUSION: ß-PPA can be assessed using en-face SLO and cross-sectional SD-OCT imaging. Correlation analyses revealed highest correlations between color SLO and FAF imaging, while correlations between SLO and SD-OCT were weak. A more precise structural definition of ß-PPA is needed.

Scanning laser 'en face' retinal imaging of epiretinal membranes.

PURPOSE: Comparison of scanning laser ophthalmoscopy (SLO) based 'en face' imaging techniques of patients with epiretinal membranes (ERM) and evaluation of the accuracy of preoperative diagnostic imaging. METHODS: A consecutive, prospective series of 53 study eyes of 46 patients with clinically diagnosed and in optical coherence tomography (OCT) confirmed symptomatic ERMs were included in this study. Spectral domain (SD-) OCT volume scans (20° × 20° with 49 horizontal sections, ART 15) including SLO en face and fundus autofluorescence (FAF) images of the macula were obtained with HRA2 (Heidelberg Retina Angiograph-Optical Coherence Tomography, Heidelberg Engineering, Heidelberg, Germany). In addition, wide-field SLO color and FAF images (Optomap 200Tx, Optos PLC, Dunfermline, UK) were performed also covering the macular area. En face images of both devices were graded for each included study eye based on SD-OCT cross sectional scans. RESULTS: Grading of SD-OCT (HRA2) based SLO en face green-blue enhanced multi-color, green reflectance, blue reflectance and standard multi-color visualization revealed a better detectability of ERM than SD-OCT-based en face infrared or FAF images or wide-field SLO (Optomap) based pseudo-color, red laser separation, green laser separation, or FAF images. Both FAF visualizations, HRA2 and Optomap based, achieved low mean scores. SD-OCT based en face thickness map visualization revealed good visualization but poor demarcation of epiretinal membranes. CONCLUSIONS: In summary, en face regular or enhanced multicolor SLO images acquired with HRA2 allow a better visualization of epiretinal membranes for preoperative evaluation compared to SD-OCT based en face thickness map or pseudo-color images acquired with Optomap while infrared or FAF images are least suitable to depict epiretinal membranes.

Megahertz ultra-wide-field swept-source retina optical coherence tomography compared to current existing imaging devices.

BACKGROUND: To investigate the image quality of wide-angle cross-sectional and reconstructed fundus images based on ultra-megahertz swept-source Fourier domain mode locking (FDML) OCT compared to current generation diagnostic devices. METHODS: A 1,050 nm swept-source FDML OCT system was constructed running at 1.68 MHz A-scan rate covering approximately 70° field of view. Twelve normal eyes were imaged with the device applying an isotropically dense sampling protocol (1,900 × 1,900 A-scans) with a fill factor of 100 %. Obtained OCT scan image quality was compared with two commercial OCT systems (Heidelberg Spectralis and Stratus OCT) of the same 12 eyes. Reconstructed en-face fundus images from the same FDML-OCT data set were compared to color fundus, infrared and ultra-wide-field scanning laser images (SLO). RESULTS: Comparison of cross-sectional scans showed a high overall image quality of the 15× averaged FDML images at 1.68 MHz [overall quality grading score: 8.42 ± 0.52, range 0 (bad)-10 (excellent)] comparable to current spectral-domain OCTs (overall quality grading score: 8.83 ± 0.39, p = 0.731). On FDML OCT, a dense 3D data set was obtained covering also the central and mid-peripheral retina. The reconstructed FDML OCT en-face fundus images had high image quality comparable to scanning laser ophthalmoscope (SLO) as judged from retinal structures such as vessels and optic disc. Overall grading score was 8.36 ± 0.51 for FDML OCT vs 8.27 ± 0.65 for SLO (p = 0.717). CONCLUSIONS: Ultra-wide-field megahertz 3D FDML OCT at 1.68 MHz is feasible, and provides cross-sectional image quality comparable to current spectral-domain OCT devices. In addition, reconstructed en-face visualization of fundus images result in a wide-field view with high image quality as compared to currently available fundus imaging devices. The improvement of >30× in imaging speed over commercial spectral-domain OCT technology enables high-density scan protocols leading to a data set for high quality cross-sectional and en-face images of the posterior segment.

Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis--potential role as biomarker of response to ranibizumab treatment.

PURPOSE: To evaluate the influence of a ranibizumab treatment on microaneurysm (MA) turnover in diabetic retinopathy. METHODS: Sixty-nine eyes were included in this retrospective study. We compared a group of 33 eyes with ranibizumab treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) images were obtained at a mean 4.76 ± 1.69 days prior to the first ranibizumab injection (baseline) and again 35.94 ± 2.44 days after the third consecutive injection in a 4-week interval. In untreated controls, images were obtained at baseline and 97.81 ± 3.16 days thereafter. Images were analyzed using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the turnover of MAs was documented and analyzed. Thereafter, MA turnover was correlated with central retinal thickness (CRT) as assessed by OCT. RESULTS: At baseline, patients in the treatment group had 5.64 ± 0.75 MAs. One month after 3 ranibizumab injections, measured MAs decreased to 4.03 ± 0.66. In the untreated control group, the initial number of 3.36 ± 0.6 MAs remained almost unchanged over 3-4 months (2.89 ± 0.57 MAs). Dynamic analysis showed that after ranibizumab treatment 3.06 ± 0.5 new MAs appeared, while 5.09 ± 0.79 disappeared. In the control group, 2.11 ± 0.4 new MAs appeared and 2.61 ± 0.48 disappeared. MA turnover was significantly higher with ranibizumab compared to the control group (8.15 ± 1.14 vs. 4.72 ± 0.81, p < 0.001). Consistently, CRT decreased from 444 to 330 µm in the ranibizumab group, while there was no change in the control group (291 vs. 288 µm). CONCLUSION: The treatment of macular edema using ranibizumab does not only reduce macular thickness, but also has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR analysis showed that more pre-existent MAs disappeared than new MAs developed, and the absolute number of MAs also decreased.

Temsirolimus inhibits proliferation and migration in retinal pigment epithelial and endothelial cells via mTOR inhibition and decreases VEGF and PDGF expression.

Due to their high prevalence, retinal vascular diseases including age related macular degeneration (AMD), retinal vein occlusions (RVO), diabetic retinopathy (DR) and diabetic macular edema have been major therapeutic targets over the last years. The pathogenesis of these diseases is complex and yet not fully understood. However, increased proliferation, migration and angiogenesis are characteristic cellular features in almost every retinal vascular disease. The introduction of vascular endothelial growth factor (VEGF) binding intravitreal treatment strategies has led to great advances in the therapy of these diseases. While the predominant part of affected patients benefits from the specific binding of VEGF by administering an anti-VEGF antibody into the vitreous cavity, a small number of non-responders exist and alternative or additional therapeutic strategies should therefore be evaluated. The mammalian target of rapamycin (mTOR) is a central signaling pathway that eventually triggers up-regulation of cellular proliferation, migration and survival and has been identified to play a key role in angiogenesis. In the present study we were able to show that both retinal pigment epithelial (RPE) cells as wells as human umbilical vein endothelial cells (HUVEC) are inhibited in proliferating and migrating after treatment with temsirolimus in non-toxic concentrations. Previous studies suggest that the production of VEGF, platelet derived growth factor (PDGF) and other important cytokines is not only triggered by hypoxia but also by mTOR itself. Our results indicate that temsirolimus decreases VEGF and PDGF expression on RNA and protein levels significantly. We therefore believe that the mTOR inhibitor temsirolimus might be a promising drug in the future and it seems worthwhile to evaluate complementary therapeutic effects with anti-VEGF drugs for patients not profiting from mono anti-VEGF therapy alone.

Anterior-segment morphology and corneal biomechanical characteristics in pigmentary glaucoma.

PURPOSE: The aim of the study reported here was to evaluate characteristics of the anterior-segment via anterior-segment optical coherence tomography (AS-OCT) and corneal biomechanical properties using an ocular response analyzer and their changes by peripheral laser iridotomy (PI) in patients with pigmentary glaucoma (PG). MATERIALS AND METHODS: Seventeen eyes with PG were included consecutively. AS-OCT and ocular response analyzer measurements were taken before and 3 months after PI. Baseline morphology and change in morphology were analyzed by correlation and multiple linear regression analysis. The main parameters assessed were anterior-chamber (AC) angles and volume as well as corneal hysteresis (CH) and corneal resistance factor. RESULTS: AC angles were found to have decreased significantly in each quadrant after PI (P<0.001), with the highest effect seen in the temporal quadrant, which decreased from 57.0°±9.6° to 44.1°±5.2° (± standard deviation). Mean AC volume decreased significantly from 213.1±36.4 to 187.0±23.4 mm(3) (P<0.001). CH and corneal resistance factor did not change after PI. CH was found to correlate with the preoperative superior and inferior angle width (Spearman's rho 0.553 and 0.615, respectively, P<0.05). Biomechanical parameters showed no predictive value on the change of AC angles or volume. CONCLUSION: PI in eyes with PG results in a highly significant reduction in the AC angles and volume as visualized by AS-OCT, with the largest effect seen in the temporal quadrant. CH is strongly positively correlated with the superior and inferior preoperative AC angles, emphasizing the importance of the biomechanical properties of the cornea for glaucoma pathogenesis in PG, but corneal biomechanical properties cannot predict PI-related AC changes.

Nonmydriatic ultra-wide-field scanning laser ophthalmoscopy (Optomap) versus two-field fundus photography in diabetic retinopathy.

The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.

Systematic analysis of wide-field fundus autofluorescence (FAF) imaging in posterior uveitis.

PURPOSE: To evaluate wide-field fundus autofluorescence (FAF) in patients with uveitis with retinal or chorioretinal involvement. MATERIALS AND METHODS: We included 78 study eyes in this prospective study. Best-corrected visual acuity, a full clinical examination, wide-field green-light FAF and composite color, green and red laser separation fundus imaging with Optomap SLO were performed. In a systematic analysis, the number, extension and margins of central and peripheral retinal or chorioretinal alterations, scars and infiltrates in infectious and non-infectious uveitic study eyes were evaluated. Wide-field FAF and color fundus imaging results were compared regarding their diagnostic properties. RESULTS: Nine out of 78 study eyes were diagnosed with infectious, 69 cases with non-infectious uveitis. Six infectious uveitic study eyes had changes of the peripheral fundus compared with 48 of 69 non-infectious uveitic eyes. In 33 (infectious versus non-infectious: 4 versus 29) cases, wide-field FAF images revealed more retinal or chorioretinal alterations or pathologies with a farther extended demarcation than wide-field composite color fundus imaging. Eleven out of 69 non-infectious study eyes were diagnosed with vasculitis which could be more precisely evaluated with wide-field FAF than wide-field composite color, green or red light filtered fundus imaging. CONCLUSIONS: Non-invasive wide-field FAF detects more retinal or chorioretinal involvement in patients with posterior uveitis than seen in color imaging and thus is useful in diagnosis and follow-up of uveitic patients.

Navigated Laser Therapy for Diabetic Macular Oedema.

Navigated laser therapy introduces computerised assistance systems to retinal laser photocoagulation treatment. Some of the main benefits the Navilas system offers over conventional laser include high precision and safety and provides additional advantages in terms of standardisation of planning, execution, documentation, quality assurance and better overall treatment comfort for the patient. Navigated laser therapy is being used with good success in the treatment of diabetic macular oedema (DMO), retinal vein occlusions (RVO) and fastpattern navigated panretinal photocoagulation in proliferative diabetic retinopathy (PDR). In centre-involving DMO, a combination of anti-vascular endothelial growth factor (VEGF) and macular laser may provide advantages over anti-VEGF monotherapy. In terms of navigated laser therapy, recent study data from our clinic and other institutions indicate that combined initial anti-VEGF and navigated macular laser therapy allows treatment success to be achieved and maintained with a significantly reduced number of interventions.

Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. METHODS: Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. RESULTS: The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. CONCLUSION: Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.

Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma.

PURPOSE: To investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects. METHODS: A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT. RESULTS: Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014). CONCLUSION: Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary.