[Real-life results of anti-VEGF treatment in fellow eyes with nAMD]. / Real-life-Ergebnisse der Anti-VEGF-Therapie bei nAMD der Partneraugen.

PURPOSE: Neovascular age-related macular degeneration (nAMD) often affects both eyes. This study compared real-life outcomes of the first affected eye (1st eye) and the last affected eye (2nd eye) after anti-vascular endothelial growth factor (anti-VEGF) treatment. MATERIAL AND METHODS: For this retrospective monocenter study 3217 eyes from 2793 patients with nAMD were identified, who received at least 3 anti-VEGF injections between 2006 and 2014 at the University Eye Hospital of Munich. Included in the study were patients with bilateral nAMD when the 1st and 2nd eyes were not previously treated and there was a strict adherence with continuous follow-up for at least 5 years. Corrected visual acuity, number of intravitreal injections and visits as well as central macular thickness were compared. RESULTS: A total of 72 eyes of 36 patients were included in this analysis. Before anti-VEGF therapy, the group of 2nd eyes showed significantly better mean visual acuity than the 1st eyes (p < 0.001). This difference in visual acuity between 1st and 2nd eyes was noted at all time points throughout the follow-up period (p < 0.05). The mean number of cumulative injections was higher in the group of 2nd eyes (p = 0.04) with a comparable number of visits between both groups. In more than half of all patients the 2nd eye became affected by nAMD within 12 months following treatment initiation of the 1st eye and the majority (83%) followed within 3 years. CONCLUSION: In unilateral nAMD, regular monitoring of the fellow eye is essential to avoid severe bilateral vision loss. Early diagnosis with rapid initiation of treatment can preserve visual acuity and quality of life.

[Optical coherence tomography biomarkers in epimacular membranes and vitreomacular traction syndrome]. / Optische Kohärenztomographie-Biomarker bei epimakulären Membranen und vitreomakulärem Traktionssyndrom.

Using high-resolution imaging, such as optical coherence tomography (OCT), the different layers of the retina as well as the vitreoretinal interface and its alterations can be very clearly differentiated. This includes the morphological characteristics of tractive maculopathies, such as epiretinal gliosis and vitreomacular traction syndrome. Additionally, structural alterations of the various layers of the neurosensory retina as a result of traction due to these pathologies can be demarcated. The latter have been investigated in clinical trials and evaluated as OCT biomarkers with respect to their prognostic and predictive value. In this review we would like to present and discuss various OCT biomarkers in the context of epimacular membranes and vitreomacular traction syndrome.

[Macular changes in optic disc pits-Optic disc pit maculopathy (ODP-M) : Pathophysiology and possibilities of surgical treatment]. / Makulaveränderungen bei Grubenpapille ­ "Optic disc pit maculopathy" (ODP-M) : Pathophysiologie und Möglichkeiten der chirurgischen Therapie.

An optic disc pit is a rare congenital abnormality of the optic nerve, which in most cases presents as a unilateral finding. Clinically, a greyish oval excavation is seen, most commonly on the temporal side of the optic nerve disc. The optic disc pit alone normally does not lead to substantial symptoms or functional limitations; however, when a maculopathy with intraretinal and/or subretinal fluid and additional other morphological changes in the macula occur, this leads to a decrease in visual acuity. With spectral domain optical coherence tomography (SDOCT) it is possible to identify the various forms of expression, which show different natural courses. Especially the presence of subretinal fluid and defects in the outer retinal layers have a poor prognosis and have the highest risk for further deterioration. Spontaneous resolution can occur but is rare. Observation is recommended in the first step. In cases of progression or pronounced deterioration, surgical intervention is indicated. Many different techniques have been proposed but there is no gold standard at the moment. Most of the surgical approaches comprise pars plana vitrectomy with peeling of the internal limiting membrane (ILM) and gas endotamponade. Newer methods, such as the ILM flap technique also show good results. Generally, it is important to know that postoperative healing and resorption of the fluid often take a long time period of up to 1 year or even longer.

Comparison of the horizontal diameter to a modeled area of traction in eyes with vitreomacular traction: is the diameter close enough to the truth?

PURPOSE: In daily practice, vitreomacular traction (VMT) is described by the horizontal diameter of its attachment site implying a regular round shape of VMT. We investigated the deviation from this circular area of vitreous traction in patients with VMT. METHODS: A retrospective analysis of optical coherence tomography (OCT) scans was performed. The area of vitreomacular attachment was determined using six radial OCT scans (Ameasured). The assumed circular area of traction was calculated based on measuring the maximal horizontal diameter for comparison (Acircular). RESULTS: Thirty-seven eyes of 37 patients with pure VMT were included. Patients' mean age was 72.8 ± 8.2 years. Mean horizontal VMT diameter was 400.8 ± 230.5 µm (median 361 µm; range 44-991 µm). While there was no difference between mean areas of traction for Acircular and Ameasured (P = 0.93), the individual difference (|Acircular - Ameasured|) was 0.042 (± 0.044) mm2 in mean or relative 73.0% (± 135.8%). A difference of ≥ 30% of Ameasured to Acircular was found in 16 eyes (43.2%) and ≥ 100% in 7 eyes (18.9%), respectively. CONCLUSION: Vitreous attachment sites possess an irregular non-circular shape in a significant number of eyes with VMT. Consequently, the area of traction appears inaccurately described by its horizontal VMT diameter alone. As the area of traction is important for therapeutic recommendation, our results emphasize the need for a more precise description of the area of traction in eyes with VMT.

[Lamellar macular holes with hyporeflective epiretinal proliferation : OCT diagnostics and clinical course]. / Makulaschichtforamen mit hyporeflektivem epiretinalem Gewebe : OCT-Diagnostik und klinischer Verlauf.

BACKGROUND: High-resolution spectral domain optical coherence tomography (SD-OCT) is the standard examination for assessment of lamellar macular holes (LMH). According to the current SD-OCT classification of LMHs, they are characterized by (1) an irregular foveal contour, (2) a defect in the inner fovea, and (3) a separation of inner retinal layers from outer retinal layers of the fovea leading to an intraretinal splitting with loss of retinal tissue. OBJECTIVE: The article aims to give an overview on the current knowledge of retinal imaging in LMH diagnostics and clinical course of disease. MATERIALS AND METHODS: This review is based on current literature and analyses of data from different case series from the Department of Ophthalmology, Ludwig-Maximilian University Munich, Germany. RESULTS: In eyes with LMH, a homogenous atypical, hyporeflective epiretinal tissue has been described in addition to conventional tractional epiretinal membranes (ERM). By SD-OCT, this named lamellar hole-associated epiretinal proliferation (LHEP) does not show common signs of traction and is characterized as a thick homogenous layer of moderately reflective material. LHEP has been demonstrated to be related to the occurrence of photoreceptor layer defects, enlargement of LMH diameter and poor visual acuity. CONCLUSION: The correlation of SD-OCT and en-face OCT can help to identify LMH subgroups and morphology progression early on. FAF enables detection of structural changes at a subclinical stage without visual deterioration. With regard to a high variability of intraretinal changes in LMHs and epimacular fibro-cellular proliferation, the current classification of LMH should be discussed and re-evaluated.

[Histopathological correlation of epiretinal tissue in lamellar macular holes and macular pseudoholes]. / Histopathologische Korrelation epiretinalen Gewebes bei Schichtforamen und Pseudoforamen der Makula.

BACKGROUND: Using high-resolution spectral domain optical coherence tomography (SD-OCT), morphologically different types of epiretinal tissue can be distinguished in lamellar macular holes (LMH) and macular pseudoholes (MPH). OBJECTIVE: This article presents the results of histopathological characterization and differentiation of epiretinal tissue in eyes with LMH and MPH, which are classified based on a morphological differentiation in SD-OCT. MATERIAL AND METHODS: This review is based on the currently available literature and own data analyses. Using SD-OCT, a differentiation into hyporeflective epiretinal tissue and contractile epiretinal membranes (ERM) was performed. For fluorescence and transmission electron microscopic analyses, epiretinal tissue harvested by pars plana vitrectomy and peeling of epiretinal tissue was processed. RESULTS: By SD-OCT hyporeflective tissue appears as a thick homogeneous layer of hypodense material located directly on the surface of the inner retina and has no visible signs of traction. Using immunocytochemistry, hyalocytes and glial cells showing no contractile activity are dominant; however, in contractile ERM in MPH, anti-alpha SMA-positive myofibroblasts are predominantly found representing the contractile element. CONCLUSION: The results of ultrastructual investigations demonstrate that morphological cell components of hyporeflective epiretinal tissue from LMH have less contractile properties than cells of contractile ERM. It can therefore be assumed that there are differences in the pathogenesis of epiretinal cell proliferation in LMH. Histopathological investigations support the hypothesis that hyporeflective epiretinal tissue represents modified material from the outer layer of the vitreous body.

[Indications and surgical approach for lamellar macular holes and pseudoholes]. / Indikation und chirurgisches Vorgehen bei Makulaschichtforamen und Pseudoforamen.

BACKGROUND: This article presents a discussion on the indications for surgical interventions of lamellar macular holes and pseudoholes. OBJECTIVE: What are the criteria for deciding on the surgical intervention for lamellar macular holes and pseudoholes? MATERIAL AND METHODS: The article is based on a literature search in PubMed RESULTS: Lamellar macular holes and pseudoholes are subdivided into degenerative and tractive alterations. Both entities are associated with relatively specific morphological and functional criteria, which correlate with the expected functional and morphological results of the surgical intervention. Patients with pseudoholes therefore profit more from a surgical intervention because alterations to the outer retina are less pronounced in these cases. CONCLUSION: The indications for surgery of lamellar macular holes and pseudoholes are established by the type of lamellar defect and the morphological and functional alterations associated with this condition.

[Clinicopathological correlations at the vitreoretinal interface]. / Klinisch-pathologische Korrelationen an der vitreoretinalen Grenzfläche.

BACKGROUND: Clinicopathological studies of the vitreoretinal interface (VRI) improve our understanding of the pathogenesis of vitreal maculopathy, facilitate differential diagnoses and help to develop new treatment strategies. OBJECTIVE: The aim of the study was to provide a comprehensive overview on clinicopathological correlations of the VRI. METHODS: A semi-structured literature search was performed in the Medline and Embase databases for relevant original studies on clinicopathological correlations of vitreal maculopathy, in addition to the latest books and review articles. RESULTS: Age-related vitreous changes with persistent vitreomacular adhesions on the retinal surface promote cellular migration and proliferation onto the vitreal side of the internal limiting membrane (ILM), thereby cementing the vitreomacular adhesions and strengthening the traction forces on retinal layers. Cellular or fibrocellular proliferation at the vitreomacular interface can be seen in all vitreal maculopathies. Furthermore, vitreoschisis in the context of anomalous posterior vitreous detachment causes the presence of vitreous cortex collagen fibrils on the vitreal side of the ILM which is associated with epiretinal membrane formation. Glial cells, hyalocytes and myofibroblasts represent the major cell types in the epiretinal cell proliferation. Glial cells and hyalocytes are capable of transdifferentiation into myofibroblasts which possess strong contractive properties and are well known for the production of extracellular matrix components. CONCLUSION: Removing vitreomacular adhesions and vitreous cortex collagen fibrils from the retinal surface is most important for successful treatment. In cases with epiretinal cell proliferation, however, removal of the ILM during macular surgery is mandatory to avoid reproliferation and recurrence. Improving the detection of epiretinal cell proliferation and cell distribution in patient eyes by optical coherence tomography or by introduction of new technologies should be addressed in the future.

[Importance of morphological and functional diagnostics of the vitreoretinal interface]. / Stellenwert morphologischer und funktioneller Diagnostik an der vitreoretinalen Grenzfläche.

Optical coherence tomography (OCT) is the standard examination for assessment of the vitreoretinal interface (VRI); therefore, it is essential to select the appropriate scan modalities to detect the total amount of morphological changes, not only at the VRI but also in all layers of the retina and in both the foveal and parafoveal areas. For the success of a surgical intervention in the treatment of vitreomacular interface disorders, morphological changes, especially in the outer retinal layers, have been determined to be of prognostic interest in high-resolution OCT. This article gives an overview of current OCT examination procedures as well as correlative aspects of morphological and functional findings.

[Epiretinal gliosis]. / Epiretinale Gliose.

Epiretinal membranes represent avascular cellular proliferations on the retinal surface, preferentially in the area of the macula. Idiopathic, primary epiretinal membranes are a relatively common finding, especially in elderly people. Other secondary pathomechanisms include retinal tears, trauma, ophthalmic surgical procedures including retinal detachment surgery, laser coagulation and cryotherapy of the retina, or as a result of inflammatory diseases. Individual symptoms depend on the degree of cellular proliferation and associated tangential traction forces at the vitreoretinal interface resulting in surface wrinkling of the retina. Patients often complain of a reduction of visual acuity accompanied by metamorphopsia. A surgical intervention using transconjunctival pars plana vitrectomy and membrane peeling is indicated depending on the reduction of visual acuity and the severity of metamorphopsia if present.

Chromovitrectomy and the vitreoretinal interface.

It still remains unclear to which extent the presence and the amount of retinal debris seen in internal limiting membrane (ILM) specimens harvested during macular surgery for macular holes or epiretinal membranes are related to the procedure of ILM peeling itself or to modifications of the surgical technique, such as application of vital dyes for visualization of the ILM, or to pathological conditions with epiretinal membrane formation at the vitreoretinal interface. The presence of cellular fragments on the retinal side of the removed ILM appears to be of multifactorial origin, and additional causes besides dye application need to be considered. However, morphological studies with evaluation of vital dyes are still of relevance and provide additional insights into the ultrastructure of the vitreoretinal interface and its interaction with adjuvants used during macular surgery. Chromovitrectomy is an emerging field in vitreoretinal surgery. It is of importance to better understand the tissue-dye interactions, which not only alter the mechanical properties of the tissue being stained, but may also have an impact on the functional result postoperatively.

Vital dyes increase the rigidity of the internal limiting membrane.

PURPOSE: To assess the stiffness of the natural human internal limiting membrane (ILM) and evaluate potential changes of the mechanical properties following staining with brilliant blue (BB) and indocyanine green (ICG). METHODS: Unstained ILM specimens were obtained during ophthalmic surgical procedures. After removal, the specimens were dissected into five parts. Two fragments were stained with BB and ICG, respectively, for 1 min, another two specimens were stained similarly followed by additional subsequent illumination using a standard light source (PENTA LUX x 50, Ophthalmologische Systeme GmbH Fritz Ruck). The fifth part served as an untreated control. All specimens were then analyzed using atomic force microscopy (AFM) in contact mode with a scan rate of 0.6 Hz. Two scan regions of 10 × 10 µm were chosen and stiffness was determined by using AFM in a force spectroscopy mode. The force curves were plotted with a data rate of 5000 Hz. In all specimens both the retinal side and vitreal side were analyzed. RESULTS: Staining resulted in a significant increase in tissue stiffness. An increase was seen both for the vitreal (BB: P<0.001; ICG: P<0.01) and retinal side (BB: P<0.01; ICG: P<0.01), with the retinal side being significantly stiffer in all control and stained samples. Additional illumination after staining did further increase tissue rigidity in most samples but not significantly. CONCLUSIONS: Staining significantly increases the stiffness of the human ILM. This might explain the fact that the stained ILM can be removed more easily and in larger fragments during vitreoretinal surgical procedures compared with unstained ILM.

An in vivo evaluation of Brilliant Blue G in animals and humans.

BACKGROUND/AIMS: To evaluate the retinal toxicity of Brilliant Blue G (BBG) following intravitreal injection in rat eyes and examine the biocompatibility and the staining properties in humans. METHODS: BBG was injected into the 11 rat eyes to evaluate toxic effects with balanced salt solution (BSS) serving as control. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts and by light microscopy 7 days later. In addition, BBG was applied during vitrectomy for macular hole (MH) (n = 15) or epiretinal membranes (ERM) (n = 3) in a prospective, non-comparative consecutive series of patients. Before and after surgery, all patients underwent a complete clinical examination including measurement of best corrected visual acuity (VA) and intraocular pressure, perimetry, fundus photography and optical coherence tomography. Patients were seen 1 day before surgery and then in approximately four weeks intervals. RESULTS: No significant reduction in RGC numbers and no morphological alterations were noted. A sufficient staining of the internal limiting membrane (ILM) was seen in patients with MH, while the staining pattern in ERM cases was patchy, indicating that parts of the ILM were peeled off along with the ERM in a variable extent. All MHs could be closed successfully. VA improved in 10 eyes (56%; 8/15 MH patients, 2/3 ERM patients), was unchanged in four eyes (22%; all MH patients) and was reduced in four eyes (22%; 3/15 MH, 1/3 ERM). No toxic effects attributable to the dye were noted during patient follow-up. The ultrastructure of tissue harvested during surgery was unremarkable. CONCLUSION: Brilliant Blue provides a sufficient and selective staining of the ILM. No retinal toxicity or adverse effects related to the dye were observed in animal and human studies. The long-term safety of this novel dye will have to be evaluated in larger patient series and a longer follow-up.

[The primary objective in macular hole surgery. Ultrastructural features of the vitreomacular interface]. / Operative Zielvorgabe in der Makulaforamenchirurgie. Neue Aspekte zur Feinstruktur der vitreomakulären Grenzfläche.

We compared the ultrastructure of the inner limiting membrane (ILM) and epiretinal tissue in closed and non-closed, idiopathic macular holes (MH). Peeling of ILM and epimacular tissue during vitrectomy was successfully performed on 77 eyes with stage III MH and on 19 eyes with stage IV MH. In 16 additional eyes with non-closed MH, we performed a second vitrectomy with extended ILM removal. The specimens were processed for transmission electron microscopy. Fibrocellular proliferation at the vitreal side of the ILM was found in 57% of MH that were closed by one operation, and in 100% of non-closed MH. Mono- and multilayered cellular membranes as well as native vitreous collagen at the ILM were significantly more frequent in eyes with stage IV MH than in eyes with stage III MH. In non-closed MH, cellular proliferation was mostly seen as irregular cell accumulation, and masses of newly formed collagen were found. Since ILM remnants and collagen represent a stimulus for the early formation of tangential traction preventing successful MH closure, it appears mandatory to create a complete vitreoretinal separation and to remove the ILM and collagen thoroughly during MH surgery.