Microbiome and Retinal Vascular Diseases.

The gut microbiome consists of more than a thousand different microbes and their associated genes and microbial metabolites. It influences various host metabolic pathways and is therefore important for homeostasis. In recent years, its influence on health and disease has been extensively researched. Dysbiosis, or imbalance in the gut microbiome, is associated with several diseases. Consequent chronic inflammation may lead to or promote inflammatory bowel disease, obesity, diabetes mellitus, atherosclerosis, alcoholic and non-alcoholic liver disease, cirrhosis, hepatocellular carcinoma, and other diseases. The pathogenesis of the three most common retinal vascular diseases, diabetic retinopathy, retinal vein occlusion, and retinal artery occlusion, may also be influenced by an altered microbiome and associated risk factors such as diabetes mellitus, atherosclerosis, hypertension, and obesity. Direct cause-effect relationships remain less well understood. A potential prevention or treatment modality for these diseases could be targeting and modulating the individual's gut microbiome.

Postoperative RNFL-Changes after Successful Trabeculectomy: 2-Year Outcomes. / Zwei-Jahres-Ergebnisse postoperativer RNFL-Entwicklung nach erfolgreicher Trabekulektomie.

BACKGROUND: The most important tool in glaucoma therapy is to lower the intraocular pressure to slow down the apoptosis of retinal ganglion cells. Trabeculectomy (TE) is considered the gold standard in glaucoma surgery. The aim of this study was to analyse the postoperative changes in retinal nerve fibre layer (RNFL) using optical coherence tomography (OCT) after TE. MATERIAL AND METHODS: We examined 40 patients naïve to prior glaucoma surgery retrospectively, who received a TE for medically uncontrolled primary open-angle glaucoma (POAG). Intraocular pressure (IOP), IOP-lowering medication, mean deviation of perimetry, visual acuity and peripapillary RNFL-thickness using OCT were evaluated during the first 24 month after TE. RESULTS: In total 40 eyes from 40 patients were treated with TE. Mean IOP decreased from 25.0 ± 0,9 to 13.9 ± 0.6 (p < 0.01), and the mean number of IOP-lowering eye drops from 3.3 ± 0.2 to 0.5 ± 0.2 (p < 0.01). Visual acuity and mean deviation in perimetry remained stable while mean global RNFL-thickness decreased from 67.8 ± 2.9 to 63.7 ± 2.9 (p < 0.01) and 63.4 ± 2.9 µm (p < 0.01) 12 and 24 months after TE. CONCLUSION: The TE is an effective method to reduce the IOD and the amount of IOP-lowering medication. Nevertheless, a significant further loss in RNFL thickness was observed in the first 12 months after TE. Thus, RNFL changes seem to stabilise only after a protracted period.

Descemet membrane endothelial keratoplasty (DMEK) improves vision-related quality of life.

PURPOSE: To evaluate vision-related quality of life (VRQL) before and after Descemet membrane endothelial keratoplasty (DMEK). METHODS: The study was conducted in patients with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy undergoing DMEK alone or in combination with cataract surgery (triple-DMEK) between August 2019 and March 2020 at the University of Leipzig Medical Center. Best-corrected visual acuity (BCVA) was measured. Visual acuity factor (VAF) and glare factor (GF) scores were calculated using the Visual Function and Corneal Health Status Instrument questionnaire answered by patients before surgery and 6 months thereafter. Subgroup analyses were performed for DMEK versus triple-DMEK, and for first versus second eyes, in addition to correlation analyses of scores with preoperative BCVA. RESULTS: Forty-six patients were included in this analysis. VAF score improved from 0.68 ± 0.54 to 0.02 ± 0.57 (P < 0.0001) and GF score improved from 0.53 ± 0.43 to -0.11 ± 0.39 (P < 0.0001) during follow-up. Both scores improved without significant differences after surgery in the first and in the fellow eye (P < 0.0001) and after DMEK and triple-DMEK (P < 0.0001). The improvement of scores did not correlate with preoperative BCVA (r = 0.06, P = 0.68 for VAF; r = -0.09, P = 0.54 for GF). CONCLUSION: VRQL improves similarly after DMEK and triple-DMEK and between first and second operated eye. The extent of improvement is independent of the preoperative BCVA. The results of this study can be useful when planning DMEK by enabling a prediction of anticipated VRQL gain.

Retinometer predicts visual outcome in Descemet membrane endothelial keratoplasty.

PURPOSE: To analyze the preoperative predictive value of retinometer visual acuity (VA) in eyes following Descemet membrane endothelial keratoplasty (DMEK). METHODS: Patients undergoing DMEK between August 2011 and July 2020 were included. Preoperative interference visual acuity was assessed using Heine Lambda 100 Retinometer. Depending on the presence or absence of concomitant ocular disease, the Retinometer was evaluated for its ability to preoperatively predict best-corrected visual acuity (BCVA) six months after surgery using correlation, simple and multiple linear regression, contingency analyses, and receiver operating characteristic (ROC) analysis. Preoperative corneal backscatter was correlated with Retinometer prediction accuracy. RESULTS: A total of 198 eyes were included in the analysis. There was a significant correlation between Retinometer VA and postoperative BCVA (r = 0.647, P < 0.001). Regardless of the presence or absence of concomitant ocular disease and the surgery procedure (DMEK & triple DMEK), Retinometer VA was the most significant predictor of postoperative BCVA (P < 0.001). ROC analysis revealed reliable diagnostic performance of the Retinometer (AUC = 0.829, P < 0.001). A Retinometer VA ≥ 0.5 accurately predicted a postoperative BCVA ≥ 0.5 in 91% of cases. No association was found between corneal backscatter and prediction accuracy (P = 0.566). CONCLUSIONS: Retinometer VA can be used for preoperative prediction of postoperative BCVA in DMEK and triple DMEK patients, independent of increased backscatter values and the presence or absence of concomitant ocular disease. By using this simple but effective tool, indication for DMEK can be facilitated and postoperative outcomes can be realistically predicted preoperatively.

Vitreoretinal Surgery in Glaucoma. / Netzhaut-Glaskörper-Chirurgie bei Glaukom.

Glaucoma is associated with the demise of retinal ganglion cells and their axons, primarily located in the retina. Vitreoretinal and glaucoma surgery overlap to a not inconsiderable extent in certain diseases. This overview article aims to present these diseases and highlight treatment strategies and the respective modes of action collectively. This article describes malignant glaucoma or aqueous misdirection syndrome, retinal surgery for choroidal detachment and expulsive choroidal hemorrhage, postoperative blebitis and endophthalmitis after glaucoma surgery, and vitrectomy after glaucoma surgery, along with the therapeutic paths for managing complications. The areas of glaucoma and vitreoretinal surgery are tightly linked. Colleagues from both subspecialties should be familiar with a certain overview of diseases concerning both subject areas.

Implantation of XEN After Failed Trabeculectomy: an Efficient Therapy? / Die XEN-Microstent-Implantation nach erfolgloser Trabekulektomie: eine sinnvolle Behandlungsoption?

BACKGROUND: Trabeculectomy (TE) has been the standard procedure in glaucoma surgery for a long time. This study examined the efficacy and safety profile of XEN45 Gel Stent (XEN) after failed and/or scarred trabeculectomy. MATERIAL AND METHODS: We analysed all files of patients, who received a XEN after insufficient TE and examined changes in intraocular pressure (IOP), IOP-lowering medication, best corrected visual acuity, visual field tests as well as the intra- and postoperative complications recorded within a 12-month follow-up period. RESULTS: 31 eyes of 28 patients were analysed in our study (mean age: 66,2 ± 13,4 years; 39% female; 48% right eye; mean follow-up after TE: 70,3 ± 64,9 months). The mean IOP decreased from 23,5 ± 6,5 to 18,0 ± 5,3 mmHg (- 23,5% compared to baseline-IOP; p = 0,01) while the mean IOP-lowering medication could be reduced from 2,8 ± 1,1 to 1,1 ± 1,5 (p < 0,01) 12 months after XEN-implantation. The mean visual acuity did not change significantly (pre-op: 0,5 ± 0,6 logMAR; 12 months post-op: 0,5 ± 0,6 logMAR). The most common complications postoperatively were choroideal detachment due to postoperative hypotony in 4 eyes (13%), a needling procedure in 9 eyes (29%), a Re-XEN-Implantation in 4 eyes (13%), an open revision of the conjunctiva in 3 eyes (10%), and a Re-TE in 1 eye (3%) as well as an Ahmed-Valve implantation in 2 eyes (6%). Overall, neither needling procedure nor further glaucoma surgery was necessary in 19 eyes (61%). In 10 of 22 evaluable eyes (45%) an IOP reduction of > 20% was achieved 12 months after XEN implantation. CONCLUSION: XEN could be an effective method to reduce IOP after failed TE. The rate of complications seems to be low and the rate of needling procedures and/or revisions is acceptable.

Foveal configurations with disappearance of the foveal pit in eyes with macular pucker: Presumed role of Müller cells in the formation of foveal herniation.

Many eyes with macular pucker are characterized by a centripetal displacement of the inner foveal layers which may result in a disappearance of the foveal pit. In this retrospective case series of 90 eyes with macular pucker of 90 patients, we describe using spectral-domain optical coherence tomography different foveal configurations with ectopic inner foveal layers, document the relationship between posterior vitreous detachment (PVD) and idiopathic epiretinal membrane (ERM) formation and spontaneous and postoperative morphological alterations of the fovea, and propose an active role of Müller cells in the development of foveal herniation. We found that ERM were formed during or after partial perifoveal PVD, or after foveal deformations caused by tissue edema. The ERM-mediated centripetal displacement of the inner foveal layers and in various eyes anterior hyaloidal traction caused a disappearance of the foveal pit and an anterior stretching of the foveola with a thickening of the central outer nuclear layer (ONL). After the edges of the thickened inner layers of the foveal walls moved together, continuous centripetal displacement of the inner foveal layers generated a bulge of the fovea towards the vitreous (foveal herniation). Macular pseudoholes with a herniation of the inner foveal layers show that the outer layer of the protruding foveal walls is the outer plexiform layer (OPL). If the ERM covered the foveal walls and parafova, but not the foveola, the inner layers of the foveal walls were not fully centripetally displaced and the foveal pit was present. The visual acuity of eyes with ectopic inner foveal layers was inversely correlated with the thickness of the foveal center. Spontaneous morphological alterations after disappearance of the foveal pit may include the development of cystoid macular edema or additional thickening of the foveal tissue and foveal herniation. The foveal configuration with ectopic inner layers of the foveal walls and a thick central ONL persisted over longer postoperative time periods. The data show that the centripetal displacement of the inner foveal layers in eyes with macular pucker, which results in a disappearance of the foveal pit, may also generate foveal herniation which is suggested to be caused by contraction of Müller cell processes in the OPL. The centripetal displacement of the inner foveal layers and the formation of foveal herniation are suggested to reverse the foveal pit formation during development.

Different modes of full-thickness macular hole formation.

Full-thickness macular holes (FTMH) are an important cause of visual deterioration. However, different modes of FTMH formation are less investigated. It is also not clear whether the development of edematous cysts contributes to FTMH formation. In this retrospective case series of 30 eyes of 30 patients, we describe using spectral-domain optical coherence tomography different modes of FTMH formation. Morphological alterations of established FTMH are shown in 5 eyes of 5 patients. We found in 2 of 30 eyes investigated that anterior hyaloidal traction induced a hyperreflectivity of the inner Müller cell layer of the foveola prior to FTMH formation. In 3 eyes, FTMH were caused by anterior hyaloidal traction which produced foveal pseudocysts that developed to an outer lamellar hole (OLH) characterized by a disruption of the central outer retina. The OLH developed to a FTMH by the disruption of the inner layer of the foveola. FTMH formation from an OLH by hyaloidal traction was observed also in further 7 eyes. In 2 eyes, the OLH, which preceded FTMH formation, was generated by a serous retinal detachment. In 3 eyes, anterior hyaloidal traction caused a detachment of the fovea from the retinal pigment epithelium (RPE); the subsequent disruption of the foveola resulted in a FTMH. Six eyes showed the development of a FTMH from a degenerative lamellar hole (DLH). In 5 eyes with macular pucker, FTMH were formed by traction of epiretinal membranes (ERM) or hyaloidal traction. Two eyes showed the development of a FTMH by anterior or tangential hyaloidal traction likely without a formation of an OLH. FTMH formation from an OLH proceeded with or without an enlargement of cystic cavities in the foveal walls. The formation of FTMH from a DLH, after a detachment of the fovea, and in macular pucker eyes was associated with a formation of cystic cavities in the foveal walls. The best-corrected visual acuity (BCVA) of eyes with an OLH or FTMH was inversely correlated to the base and minimum diameters of the holes, and with the height of the foveal walls; the highest correlation coefficients were found between the BCVA and the base diameter. The data show that FTMH may be formed via different modes by hyaloidal traction and/or traction of ERM, or after a serous retinal detachment. It is suggested that, after FTMH formation, the impaired fluid clearance through the RPE after detachment of the central outer retina causes the development of edematous cysts in the foveal walls which enlarges the FTMH. The BCVA of eyes with an OLH or FTMH mainly depends on the size of the central photoreceptor-free area.

Neuroprotective effects of glial mediators in interactions between retinal neurons and Müller cells.

Progressive retinal ganglion cell (RGC) loss underlies a number of retinal neurodegenerative disorders, which may lead to permanent vision loss. However, secreted neuroprotective factors, such as PEDF, VEGF and IL-6, which are produced by Müller cells, have been shown to promote RGC survival. Assuming that the communication of RGCs with Müller cells involves a release of glioactive substances we sought to determine whether retinal neurons are able to modulate expression levels of Müller cell-derived PEDF, VEGF and IL-6. We demonstrate elevated mRNA levels of these factors in Müller cells in co-cultures with RGCs or R28 cells when compared to homotypic Müller cell cultures. Furthermore, R28 cells were more protected from apoptosis when co-cultured with Müller cells. IL-6 and VEGF were upregulated in Müller cells under hypoxia. Both cytokines, as well as PEDF, induced an altered neuronal expression of members of the Bcl-2 family, which are central molecules in the regulation of apoptosis. These results suggest that in retinal ischemia, via own secreted mediators, RGCs can resist a potential demise by stimulating Müller cells to increase production of neuroprotective factors, which counteract RGC apoptosis.

Retinal nerve fibre layer thickness measurements in childhood glaucoma: the role of scanning laser polarimetry and optical coherence tomography.

PURPOSE: A central diagnostic tool in adult glaucoma is the peripapillary retinal nerve fibre layer (pRNFL) thickness. It can be assessed by scanning laser polarimetry (SLP) or optical coherence tomography (OCT). However, studies investigating the relevance of pRNFL measurements in children are rare. This study aims to compare the glaucoma diagnosing ability of SLP and OCT pRNFL thickness measurements in a paediatric population. METHODS: This retrospective study included 105 children (glaucoma: 22 (21.0%); healthy glaucoma suspects: 83 (79.0%)) aged 4-18 years, examined with SLP (GDxPro/ECC, Carl Zeiss Meditec) and spectral-domain OCT (SPECTRALIS®, Heidelberg Engineering). The thickness of pRNFL sectors was compared between diseased and healthy participants. Areas under the receiver-operating characteristic curves (AUC) and logistic regression results were used to compare the glaucoma discriminative capacity between SLP and OCT measurements. RESULTS: Using OCT, pRNFL thickness was decreased in the superior, nasal, and inferior quadrants of glaucoma patients compared to healthy controls (P < 0.001, each). With SLP, such a difference was only observed in the inferior quadrant (P = 0.011). A correlation between glaucoma diagnosis and OCT-measured pRNFL thickness was found in all quadrants (P < 0.001) other than the temporal. With SLP, a correlation was found for the total average thickness (P = 0.037) and inferior quadrant (P = 0.0019). Finally, the AUCs of OCT measurements were markedly higher than those of SLP (e.g., inferior quadrant: OCT 0.83, SLP 0.68). CONCLUSION: pRNFL thickness measurements using both OCT and SLP, correlate notably with the presence of glaucoma. In general, the diagnostic performance of pRNFL thickness measurements seems higher for OCT than for SLP. Thus, pRNFL thickness measurements could provide important information, complementing conventional clinical and functional parameters in the diagnostic process of paediatric glaucoma.

Degenerative lamellar macular holes: tractional development and morphological alterations.

PURPOSE: The development of degenerative lamellar macular holes (DLH) is largely unclear. This study was aimed at documenting with spectral-domain optical coherence tomography the tractional development and morphological alterations of DLH. METHODS: A retrospective case series of 44 eyes of 44 patients is described. RESULTS: The development of DLH is preceded for months or years by tractional deformations of the fovea due to the action of contractile epiretinal membranes (ERM) and/or the partially detached posterior hyaloid, or by cystoid macular edema (CME). DLH may develop after a tractional stretching and thickening of the foveal center, from a foveal pseudocyst, after a detachment of the foveola from the retinal pigment epithelium, a disruption of the foveal structure due to CME, and after surgical treatment of tractional lamellar or full-thickness macular holes (FTMH). The foveal configuration of a DLH can be spontaneously reestablished after short transient episodes of CME and a small FTMH. A DLH can evolve to a FTMH by traction of an ERM. Surgical treatment of a DLH may result in an irregular regeneration of the foveal center without photoreceptors. CONCLUSIONS: Tractional forces play an important role in the development of DLH and in the further evolution to FTMH. It is suggested that a DLH is the result of a retinal wound repair process after a tractional disruption of the Müller cell cone and a degeneration of Henle fibers, to prevent a further increase in the degenerative cavitations.

Outcome of a single XEN microstent implant for glaucoma patients with different types of glaucoma.

BACKGROUND: The aim of this retrospective study was to compare the efficacy and safety profile of a single XEN-microstent in different types of primary and secondary open angle glaucoma. METHODS: A single XEN microstent was implanted in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pseudoexfoliation glaucoma (PEX) and secondary glaucoma (Sec.Gl). The intraocular pressure (IOP), the active substances of the applied IOP-lowering drugs, the best corrected visual acuity (BCVA) and the mean deviation (MD) of the perimetry were measured at baseline and at regular follow-ups, scheduled at 2 days and 1, 3, 6 and 12 months after surgery. RESULTS: 153 eyes were included in this analysis. 113 eyes were affected by POAG (74%), 5 eyes by NTG (3%), 22 eyes by PEX (14%) and 13 eyes by Sec. Gl (9%). Mean IOP decreased in all treatment groups during the 12 months of follow-up (complete group: 23.9 ± 7.4 to 15.4 ± 5.1 mmHg (p < 0.01); POAG: 22.8 ± 6.5 to 15.1 ± 4.6 mmHg (p < 0.01); NTG: 16.6 ± 3.4 to 11.6 ± 2.2 mmHg (p < 0.05); PEX: 28.0 ± 7.9 to 17.1 ± 6.6 mmHg (p < 0.01); Sec.Gl: 28.9 ± 13.9 to 15.5 ± 6.9 mmHg (p < 0.05)). In the 153 eyes the average number of IOP-lowering drugs applied decreased from 2.6 ± 1.2 to 0.8 ± 1.3 12 months after surgery (p < 0.01). BCVA and mean deviation of automated standard perimetry remained stable in all groups during follow-up. CONCLUSION: As in eyes suffering from POAG, IOP and number of IOP-lowering drugs applied can be effectively reduced by XEN implantation in eyes suffering from NTG, PEX and secondary glaucoma while leaving BCVA and visual field unchanged. TRIAL REGISTRATION: Trial was registered at DRKS (registration number: DRKS00020800 , Registered 25.February 2020 - Retrospectively registered).

Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons.

The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.

[Secondary Neuroprotection in Glaucoma by Reduction of Intraocular Pressure]. / Sekundäre Neuroprotektion beim Glaukom durch Augendrucksenkung.

The central goal of glaucoma treatment is the reduction of intraocular pressure (IOP) by means of medication and/or surgery, in order to prevent further disease progression for as long as possible. Stabilising visual field defects and saving papillary neural tissue are seen as the optimal achievable aims in glaucoma therapy. We performed a systematic literature search and analysis of the published articles dealing with neuroprotection and functional improvement by IOP reduction in glaucoma. On this basis, the known options for anatomical and functional recovery of formerly lost structures and functions will be elucidated. Several studies - some large - have provided evidence for anatomical improvement at the optic nerve head and functional improvement in the results of visual field tests. After glaucoma treatment, there is anatomical and functional improvement in some patients. However, improvement is mostly detectable in patients whose IOP was greatly reduced.

[Analysis of Glaucomatous Changes of the Macula Using Optical Coherence Tomography]. / Analyse glaukombedingter Makulaveränderungen mittels optischer Kohärenztomografie.

BACKGROUND: In glaucoma, progressive retinal nerve fibre loss can be measured in the peripapillary and macular regions using optical coherence tomography (OCT). The goal of this study was to evaluate the impact of glaucoma on all measureable retinal layers using the spectral domain OCT (SD-OCT). MATERIALS AND METHODS: SD-OCT scans using automated retinal layer segmentation were performed in both eyes of primary open-angle glaucoma patients with strictly monocular absolute visual field scotoma in the central 10° of their visual field. The same measurements were performed in one eye per person in a healthy age-matched control group. The mean thickness of all retinal layers in the central 24 × 24° of the macular region was compared between groups. RESULTS: SD-OCT scans were performed in 24 eyes of 12 glaucoma patients (10 female, 2 male) with a mean age of 72.3 ± 8.1 years and in 12 eyes of 12 healthy controls (9 female, 3 male) with a mean age of 66,0 ± 7,6 years. Statistically significant thickness differences between the glaucomatous and the healthy eyes could be demonstrated for the retinal nerve fibre layer, the ganglion cell layer, the inner plexiform layer and the complete retinal thickness, with lower mean thicknesses in the glaucoma group. CONCLUSION: Using SD-OCT, single retinal layers of the macular region can be scanned and measured automatically. In glaucoma, a decrease in thickness of the inner retinal layers containing ganglion cells and their axons or dendrites could be demonstrated compared to healthy eyes. No corresponding difference in thickness could be found for the outer retinal layers using SD-OCT measurements.

Two different populations of Müller cells stabilize the structure of the fovea: an optical coherence tomography study.

PURPOSE: To document with spectral-domain optical coherence tomography the structural stabilization of the fovea and the sealing of outer macular defects by Müller cells. METHODS: A retrospective case series of 45 eyes of 34 patients is described. RESULTS: In cases of a cystic disruption of the foveola as in macular telangiectasia type 2 and vitreomacular traction, the Müller cell cone provides the structural stability of the fovea. In cases of a detachment or disruption of the Müller cell cone, e.g., in foveal pseudocysts, outer lamellar holes, and degenerative and tractional lamellar holes, Müller cells of the foveal walls may provide the structural stability of the fovea by the formation of a hyperreflective external limiting membrane (ELM) which bridges the holes in the central outer nuclear layer (ONL). Müller cells of the foveal walls and parafovea mediate the regeneration of the foveal architecture in cases of outer lamellar and full-thickness macular holes. The regeneration proceeds by a centripetal displacement of photoreceptor cell somata which closes the holes in the central ONL. The closure may be supported by the formation of a glial tissue band at the ELM which seals the hole. CONCLUSIONS: The Müller cell cone provides the foveal stability in cases of a cystic disruption of the foveola. The structural stability of the outer foveal layers is mainly provided by the Müller cells of the foveal walls and parafovea; these cells also mediate the regeneration of the outer fovea in cases of a defect of the central ONL.

Prognostic Factors in Patients with Persistent Full-Thickness Idiopathic Macular Holes Treated with Re-Vitrectomy with Autologous Platelet Concentrate.

PURPOSE: To identify the predictors for anatomical and functional outcome after re-vitrectomy with application of autologous platelet concentrate (APC) in eyes with persistent idiopathic macular hole (MH). METHODS: Retrospective study of 103 eyes with persistent MHs after vitrectomy with peeling of internal limiting membrane (ILM) and expansive gas. All patients underwent re-vitrectomy with APC and endotamponade. The anatomical MH closure rate and postoperative best-corrected visual acuity (BCVA) were evaluated. Further, predictive factors influencing the success of the surgery were analyzed. RESULTS: Median BCVA (logMAR) before the surgery was 1.00 (interquartile range [IQR] 0.80-1.30) and the median of minimum diameter between hole edges was 508 µm (IQR 387-631). The final closure rate after re-vitrectomy with APC was 60.2% (62 of 103 eyes). The following predictors were identified to significantly influence the closure rate: tractional hole index (THI), axial length, time between first and second surgery, and the experience of the surgeon (p < 0.05). CONCLUSIONS: Re-vitrectomy with APC led to the closure of 60.2% of the persistent MHs. The closure rate negatively correlates with increasing axial length, time between the first and second surgery, and the decreased THI. Further, experienced surgeons (with a history of >100 pars plana vitrectomies with ILM peeling) had significantly higher closure rates.

Comparing the efficacy of trabeculectomy and diode laser cyclophotocoagulation in primary open-angle glaucoma.

PURPOSE: The aim was to compare the postsurgical outcomes of trabeculectomy (TET) and transscleral cyclophotocoagulation (CPC) in a similar cohort of eyes diagnosed with primary open-angle glaucoma (POAG). MATERIALS AND METHODS: For this monocentric non-randomized retrospective comparative trial, the records of eyes which underwent TET or CPC between 2013 and 2016 at our institution for the treatment of POAG were reviewed. Parameters analyzed before surgery as well as 1 and 2-3 years afterwards were visual acuity (VA), intraocular pressure (IOP), mean defect (MD) of the visual field, number of glaucoma medications and the objective refraction using which the surgically induced astigmatism (SIA) was calculated. RESULTS: In total, 51 eyes of 51 patients underwent TET and 45 eyes of 45 patients underwent CPC. Mean VA dropped in both groups on the last follow-up after surgery (TET-group: 0.17 ± 0.17 to 0.23 ± 0.28 logMAR, p = 0.01/CPC-group: 0.22 ± 0.22 to 0.26 ± 0.27 logMAR, p = 0.01). In the TET- and CPC-groups IOP decreased significantly (TET: 24.9 ± 6.4 to 14.9 ± 3.1 mmHg, p = 0.001/CPC: 23.0 ± 6.5 to 16.0 ± 4.1 mmHg, p = 0.001) although more pronounced and less depending on IOP-lowering medication in eyes after TET. MD remained stable after TET (7.4 ± 4.8 and 8.1 ± 4.9 dB, p = 0.1) but further deteriorated in eyes after CPC (9.0 ± 4.9 and 10.7 ± 4.6 dB, p < 0.001). SIA was comparable in both groups on the last follow-up (TET: 0.83 ± 0.69 D; CPC: 0.91 ± 0.65 D, p = 0.6). CONCLUSION: The IOP reduction achieved without medication was more pronounced in the TET-group compared with the CPC-group. Visual field remained stable in the TET-group, while further deteriorating in the CPC-group during follow-up. Eyes undergoing CPC had a higher demand for additional medication to reach comparable success rates as TET. Due to this performing TET is favorable over CPC in POAG eyes.

[Protective Effects of Müller Glia Cells Towards Retinal Ganglion Cells]. / Der protektive Einfluss Müllerʼscher Gliazellen auf retinale Ganglienzellen.

INTRODUCTION: Müller glial cells carry out different tasks to warrant normal retinal functions. The aim of this study was to investigate if Müller cells also support retinal ganglion cells (RGC). MATERIALS AND METHODS: RGC were cultured for 24 hours in the presence or absence of Müller glial cells under normoxic (20% O2, 5% CO2) or hypoxic (0.2% O2, 5% CO2, 94.8% N2) culture conditions. The number of vital RGC and the length of the newly developed neurites were evaluated. RESULTS: Under normoxic conditions, RGC vitality was significantly higher (p < 0.01) when cultured with Müller cells (62.85 ± 2.06%) than without (47.29 ± 2.83%). Under hypoxia, RGC vitality was significantly higher (p < 0.01) in co-cultures (41.07 ± 2.28%) than in homotypic RGC cultures (28.49 ± 2.16%). The maximum length of the newly developed neurites was found in the normoxic co-culture (90.7 ± 7.4 µm), but showed only a minor difference (p = 0.04) when compared to the normoxic homotypic RGC culture. CONCLUSION: Müller glial cells support RGC under normoxic and hypoxic culture conditions. Length of newly developed neurites and number of surviving RGC are both parameters to evaluate cell vitality.

Müller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation.

Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. METHODS: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells. RESULTS: Secreted mediators of Müller cells increased survival of RGCs under normoxia or hypoxia to a similar degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3 activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs. Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R attenuated MCM-induced STAT3 activation and compromised the viability of PEDF-exposed R28 cells. CONCLUSIONS: Müller cells are an important source of PEDF, which promotes RGC survival through STAT3 activation and, at least in part, via PEDF-R. Enhancing the secretory function of Müller cells may be useful to promote RGC survival in retinal neurodegenerative diseases.