Ultrastructural Details of Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of this study was to describe differences in the vitreomacular interface (VMI) in idiopathic epiretinal membrane (ERM) foveoschisis compared to macular pseudohole (MPH) and lamellar macular hole (LMH). METHODS: We analysed surgically excised epiretinal material and internal limiting membrane (ILM) specimens obtained from 16 eyes of 16 patients with ERM foveoschisis (6 eyes), MPH (5 eyes), and LMH (5 eyes) during standard pars plana vitrectomy (PPV) with membrane peeling. The three entities were classified according to the newly introduced optical coherence tomography (OCT) terminology. Transmission electron microscopy (TEM) was used to describe the ultrastructural features. RESULTS: We found fibrocellular epiretinal tissues in all samples analysed. However, the cell and collagen composition of the VMI differed between groups. Eyes with ERM foveoschisis were characterized by a higher number of cells, multilayered membranes, and thick strands of vitreous collagen embedding the major cell types of myofibroblasts compared to MPH. Eyes with MPH also showed a predominance of myofibroblasts, but these were located directly on the ILM with no collagen between the cells and the ILM. Eyes with LMH showed a thick, multilayered epiretinal proliferation consisting mainly of non-tractional glial cells, corresponding to hypodense epiretinal proliferation on OCT. Eyes with ERM foveoschisis and MPH were more likely to have incomplete PVD compared to LMH in terms of posterior hyaloid status. DISCUSSION/CONCLUSION: Tractional ERMs in eyes with ERM foveoschisis and MPH differ in their ultrastructure. The main difference is in the amount and topographical distribution of vitreous collagen. However, the epiretinal cell types are predominantly myofibroblasts in both entities. This highlights the importance of distinguishing ERM foveoschisis from both MPH and LMH in terms of pathogenesis and surgical peeling procedures.

[Current aspects of vernal and atopic keratoconjunctivitis]. / Aktuelles zur Keratoconjunctivitis vernalis und atopica.

BACKGROUND: Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are complex and rare diseases. Thus, their diagnosis and treatment are often a challenge. OBJECTIVE: Discussion on the epidemiology, new pathogenetic concepts, interesting clinical findings, diagnostic possibilities and new treatment options and their side effects in severe ocular allergies. Analysis of the presentation of VKC in the internet. MATERIAL AND METHODS: Evaluation of recent review articles, original publications, and case reports on the topics of VKC and AKC over the past 5 years. RESULTS: Ocular allergies have significantly increased over the last decades. Recent concepts discussed in the pathogenesis of VKC and AKC are the role of the local and gut microbiome as well as the influence of neuroinflammation. Keratoconus is significantly more common in patients with VKC and AKC compared to the normal population. It is associated with faster progression and a more severe course of disease. A conjunctival provocation test is only rarely necessary in the diagnosis of allergic conjunctivitis. Treatment of atopic dermatitis with dupilumab, an interleukin 4 receptor alpha (IL-4Ra) antagonist, can cause ocular side effects. Unfortunately, information available on the internet for patients and parents on the topic of VKC is sometimes dangerously incorrect. CONCLUSION: From the abovementioned new pathogenetic concepts, preventive and personalized treatment options could be developed in the future. Keratoconus in AKC/VKC must be recognized and treated early. Official guidelines are now available for a standardized conjunctival provocation test in the diagnosis of allergic conjunctivitis. The unwanted ocular side effects of dupilumab are often difficult to discriminate from the actual underlying AKC and respond well to anti-inflammatory treatment. Patients with VKC must be informed about the incorrect information on the internet regarding their disease.

One-stage versus two-stage bilateral implantable collamer lens implantation: a comparison of efficacy and safety.

Implantable collamer lens implantation (ICL) represents a safe and effective treatment for myopia and myopic astigmatism. To compare the outcomes of a bilateral one-stage same day approach to a two-stage approach, the databases of the University Eye Hospital Munich, Ludwig Maximilians-University and Smile Eyes Linz, Austria were screened for eyes that had undergone ICL implantation. Two-stage surgery was performed at an interval of 1 day (17 patients), 2 days (19 patients) and 1 week (2 patients). Variables analyzed were preoperative, 1-day and last follow-up uncorrected distance (UDVA) and corrected distance visual acuity (CDVA), manifest refraction, refractive spherical equivalent (SEQ), astigmatism, age, endothelial cell count (ECD), intraocular pressure (IOP) and ICL vaulting. In total, 178 eyes (100 eyes one-stage, 78 eyes two-stage) of 89 patients were included in this study. Mean follow-up was 1.1 ± 0.8 and 1.3 ± 0.5 years. Mean preoperative SEQ was - 7.9 ± 2.6 diopters (D) in the one-stage and - 8.0 ± 1.7 D in the two-stage group (p = 0.63) and improved to 0.00 ± 0.40 and - 0.20 ± 0.40 D at end of follow-up, showing slightly better stability in the one-stage group (p = 0.004). There was no difference in the efficacy (1.1 vs. 1.2, p = 0.06) and the safety index (1.2 vs. 1.2, p = 0.60) between the two groups. No eye (0%) in either group lost 2 lines or more of UDVA (p > 0.99). Refraction within ± 0.50 D and ± 1.00 D around target was achieved comparably often (89 vs. 86%, p = 0.65; 99 vs. 99%, p > 0.99). Endothelial cell loss was slightly higher in the two-stage group (1.3 vs. 4.3%). Vaulting at the final follow up was higher in the one-stage group (373.8 ± 205.4 µm vs. 260.3 ± 153.5 µm, p = 0.00007). There were no serious intraoperative complications in either group. In conclusion, this study demonstrates that both the one- and two-stage approaches are equally effective, predictable and safe. Regarding endothelial cell loss, vaulting and SEQ stability, the one-stage group showed slightly better outcomes, but these results are clinically questionable because they are so small. Larger studies are needed to quantitatively evaluate a potential benefit.

[New and future treatment approaches for allergic conjunctivitis]. / Neue und zukünftige Therapieansätze in der Behandlung der allergischen Konjunktivitis.

BACKGROUND: In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief. OBJECTIVE: Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given. MATERIAL AND METHODS: Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented. RESULTS: In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T­helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC). CONCLUSION: A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.

Accuracy of toric intraocular lens power calculation depending on different keratometry values using a novel network based software platform.

Purpose: To compare different corneal keratometry readings (swept-source-OCT-assisted biometry and Scheimpflug imaging) with a novel software platform for calculation of toric intraocular lenses. Setting: Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany. Design: Retrospective, non-randomized, clinical trial. Methods: Twenty-three eyes undergoing toric intraocular lens implantation were included. Inclusion criteria were preoperative regular corneal astigmatism of at least 1.00 D, no previous refractive surgery, no ocular surface diseases and no maculopathies. Lens exchange was performed with CALLISTO eye (Zeiss). For each patient, the expected postoperative residual refraction was calculated depending on three different corneal parameters of two different devices: standard K-front (K) and total keratometry (TK) obtained by a swept-source-OCT-assisted biometry system (IOL Master 700, Zeiss) as well as total corneal refractive power (TCRP) obtained by a Scheimpflug device (Pentacam AXL, Oculus). Barrett's formula for toric intraocular lenses was used for all calculations within a novel software platform (EQ workplace, Zeiss FORUM®). Results were statistically compared with postoperative refraction calculated according to the Harris dioptric power matrix. Results: The standard K values (mean PE 0.02 D ± 0.45 D) and TK values (mean PE 0.09 D ± 0.43 D) of the IOL Master 700 reached similar results (p = 0.96). 78% of eyes in both K and TK groups achieved SE within ±0.5 D of attempted correction and all eyes (100%) were within ±1.0 D of attempted correction in both groups. By contrast, the prediction error in the IOL calculation using the TCRP of the Scheimpflug device was significantly greater (mean PE -0.56 D ± 0.49 D; p = 0.00 vs. standard K and p = 0.00 vs. TK) with adjusted refractive indices. Thirty-nine and Ninety-one percentage of eyes in the TCRP group achieved SE within ±0.5 D (p = 0.008 K vs. TCRP and p = 0.005 TK vs. TCRP) and ± 1.0 D (p = 0.14 vs. TCRP) of attempted correction, respectively. Conclusion: All three corneal parameters (standard K, TK, TCRP) performed well in calculating toric IOLs. The most accurate refractive outcomes in toric IOL implantation were achieved by IOL calculations based on swept-source-OCT-assisted biometry. The SS-OCT-based K-front and TK values achieve comparable results in the calculation of toric IOLs.

Intraocular lens power calculation using total keratometry and ray tracing in eyes with previous small incision lenticule extraction - A case series.

Purpose: To assess the IOL power calculation accuracy in post-SMILE eyes using ray tracing and a range of total keratometry based IOL calculation formulae. Observations: Ray tracing showed excellent predictability in IOL power calculation after SMILE and its accuracy was clinically comparable with the Barrett TK Universal II and Haigis TK formula. Conclusions and importance: Incorporating posterior corneal curvature measurements into IOL power calculation after SMILE seems prudent. The ray tracing method as well as selected TK-based formulae yielded excellent accuracy and should be favored in post-SMILE eyes.

Enhancing ectasia screening using advanced AS-OCT: a case series of challenging refractive candidates.

Purpose: Ectasia screening in candidates for laser refractive surgery is mandatory during preoperative evaluation. Despite the availability of modern imaging techniques, refractive surgeons often face borderline decisions when patients present with suspicious tomographic findings. This case series presents refractive candidates with suspicious tomographic findings and demonstrates how to interpret them using Scheimpflug imaging and additional anterior segment optical coherence tomography (AS-OCT). Setting: Department of Ophthalmology, University Hospital, LMU Munich. Case series: This case series examines six potential candidates for refractive surgery with a mean age of 29.2 ± 3.9 years, whose corneal assessments using Scheimpflug imaging raised suspicion for ectasia. Each candidate was additionally examined with AS-OCT and reevaluated. The mean manifest subjective spherical equivalent was -3.67 ± 1.8 diopters. The total corneal thickness measured 537 µm ± 30 µm at its thinnest point. None of the candidates had any reported underlying corneal or ophthalmic diseases, and slit lamp examinations revealed no abnormal morphological findings. Conclusions: Both Scheimpflug imaging and AS-OCT are appropriate tools for screening refractive candidates for ectasia. While topographic and elevation analyses yielded comparable results regarding corneal structure, the epithelial mapping provided by AS-OCT played a critical role in decision-making for cases with borderline tomographic findings. Establishing a global consensus on the use of epithelial mapping in ectasia screening is necessary.

[Macular hole: Differential diagnosis, treatment options and new guideline recommendations]. / Makulaforamen: Differenzialdiagnose, Behandlungsoptionen und neue Leitlinienempfehlungen.

Full-thickness macular holes (FTMH) usually result in a pronounced reduction of visual acuity and represent one of the most frequent indications for retinal surgery. If diagnosed and treatment is initiated at an early stage, surgery has a high success rate with respect to both hole closure and improvement of visual acuity. Optical coherence tomography (OCT)-based staging and sizing enables an estimation of the surgical outcome. The differential diagnostic distinction from clinically similar disorders, such as lamellar macular holes, macular pseudoholes, and foveoschisis is clinically relevant as the pathogenesis, prognosis and treatment are significantly different. While vitrectomy with peeling of the inner limiting membrane (ILM) and gas tamponade is established as the standard treatment for FTMH, some aspects of treatment are handled differently between surgeons, such as the timing of surgery, the choice of endotamponade and the type and duration of postoperative positioning. For FTMH associated with vitreomacular traction, alternative treatment options in addition to vitrectomy include intravitreal ocriplasmin injection and pneumatic vitreolysis. The current clinical guidelines of the German ophthalmological societies summarize the evidence-based recommendations for diagnosis and treatment of FTMH.

[Vitreomacular traction: diagnostics, natural course, treatment decision and guideline recommendations]. / Vitreomakuläre Traktion: Diagnostik, natürlicher Verlauf, Therapieentscheidung und Leitlinienempfehlungen.

Vitreomacular traction is a tractive foveolar adhesion of the posterior vitreous limiting membrane, resulting in pathological structural alterations of the vitreomacular interface. This must be differentiated from physiological vitreomacular adhesion, which exhibits a completely preserved foveolar depression. Symptoms depend on the severity of the macular changes and typically include reduced visual acuity, reading problems and metamorphopsia. High-resolution spectral domain optical coherence tomography (SDOCT) imaging enables classification of the sometimes only subtle morphological changes. If pronounced vitreomacular traction is accompanied by epiretinal gliosis and alterations to the outer retina, it is referred to as a vitreomacular traction syndrome. Vitreomacular traction has a high probability of spontaneous resolution within 12 months. Therefore, treatment should only be carried out in cases of undue suffering of the patient and with symptoms during bilateral vision and a lack of spontaneous resolution. In addition to pars plana vitrectomy, alternative treatment options, such as intravitreal injection of ocriplasmin and pneumatic vitreolysis are discussed for vitreomacular traction with an associated macular hole; however, ocriplasmin is no longer available in Germany. The best anatomical results in comparative investigations were achieved by vitrectomy. Pneumatic vitreolysis is controversially discussed due to the increased risk of retinal tears. In one of the current S1 guidelines of the German ophthalmological societies evidence-based recommendations for the diagnostics and treatment of vitreomacular traction are summarized.

[Epiretinal membrane: diagnostics, indications and surgical treatment]. / Epiretinale Gliose: Diagnostik, Indikationsstellung und chirurgische Therapie.

An epiretinal membrane (ERM) is a frequently occurring disease affecting the macula, which can be associated with visual impairment and metamorphopsia, depending on the severity and location. A distinction is made between an idiopathic form caused by age-related changes of the vitreous body and a secondary form associated with diseases of the posterior segment. The development of fibrocellular epiretinal membranes formed by dedifferentiation of intraretinal and extraretinal cells at the level of the vitreomacular interface plays a major role in the pathogenesis. The diagnostics and indications for surgical treatment of ERM are based on the visual acuity, evidence of metamorphopsia, ophthalmoscopic findings and optical coherence tomography (OCT) of the macula. In addition to the possibility of observation of the course where benign spontaneous courses are not uncommon, pars plana vitrectomy (PPV) with peeling of the ERM and internal limiting membrane (ILM) to prevent recurrences is the treatment of choice in symptomatic patients. The prognosis after surgical treatment is very good. In approximately two thirds of the cases, an improvement in visual acuity and/or a reduction of metamorphopsia can be achieved, with a number of predictive, primarily OCT-based factors enabling a prediction of the functional prognosis. Comprehensive patient education regarding the generally long duration of postoperative rehabilitation and the possibility of persistent symptoms or visual deterioration despite successful membrane removal is essential.

Epithelial Remodeling and Epithelial Wavefront Aberrometry after Spherical vs. Cylindrical Myopic Small Incision Lenticule Extraction (SMILE).

Background/Objectives: To compare the epithelial thickness changes and the changes in epithelial wavefront aberrometry following spherical versus astigmatic myopic small incision lenticule extraction (SMILE). Methods: Eighty-six eyes of 86 patients who underwent SMILE were included in this retrospective study. A total of 43 eyes underwent myopic spherical correction (spherical group) and 43 eyes underwent myopic cylindrical correction (cylindrical group). The groups were matched according to the spherical equivalent of surgically corrected refraction. Subjective manifest refraction as well as high-resolution anterior segment optical coherence tomography (MS-39; CSO; Florence, Italy) were obtained preoperatively as well as 3 months postoperatively. The latter was utilized for computing epithelial wavefront aberrometry in addition to epithelial thickness mapping. Results: Epithelial thickness increased significantly in both groups after SMILE (p < 0.01). In the cylindrical group, epithelial thickening was more pronounced on the flat meridian compared to the steep meridian (p = 0.04). In both groups, epithelial wavefront aberrometry showed a significant postoperative increase in the epithelium's spherical refractive power, causing a myopization of -0.24 ± 0.42 diopters (D) in the spherical group (p < 0.01) and -0.41 ± 0.52 D in the cylindrical group (p < 0.0001). While no significant changes in epithelial cylindrical refractive power were observed in the spherical group, a significant increase was noted in the cylindrical group from -0.21 ± 0.24 D to -0.37 ± 0.31 D (p = 0.01). In both groups, epithelial higher-order aberrations increased significantly (p < 0.001). Conclusions: Postoperative epithelial remodeling after SMILE alters lower-order (sphere and cylinder) and higher-order aberrations of the corneal epithelial wavefront and might contribute to refractive undercorrection, especially in astigmatic corrections. Epithelial wavefront aberrometry can be used to quantify the refractive effect of epithelial remodeling processes after keratorefractive surgery.

Evaluation of OCT biomarker changes in treatment-naive neovascular AMD using a deep semantic segmentation algorithm.

OBJECTIVES: To determine real-life quantitative changes in OCT biomarkers in a large set of treatment naive patients in a real-life setting undergoing anti-VEGF therapy. For this purpose, we devised a novel deep learning based semantic segmentation algorithm providing the first benchmark results for automatic segmentation of 11 OCT features including biomarkers for neovascular age-related macular degeneration (nAMD). METHODS: Training of a Deep U-net based semantic segmentation ensemble algorithm for state-of-the-art semantic segmentation performance which was used to analyze OCT features prior to, after 3 and 12 months of anti-VEGF therapy. RESULTS: High F1 scores of almost 1.0 for neurosensory retina and subretinal fluid on a separate hold-out test set with unseen patients. The algorithm performed worse for subretinal hyperreflective material and fibrovascular PED, on par with drusenoid PED, and better in segmenting fibrosis. In the evaluation of treatment naive OCT scans, significant changes occurred for intraretinal fluid (mean: 0.03 µm3 to 0.01 µm3, p < 0.001), subretinal fluid (0.08 µm3 to 0.01 µm3, p < 0.001), subretinal hyperreflective material (0.02 µm3 to 0.01 µm3, p < 0.001), fibrovascular PED (0.12 µm3 to 0.09 µm3, p = 0.02) and central retinal thickness C0 (225.78 µm3 to 169.40 µm3). The amounts of intraretinal fluid, fibrovascular PED, and ERM were predictive of poor outcome. CONCLUSIONS: The segmentation algorithm allows efficient volumetric analysis of OCT scans. Anti-VEGF provokes most potent changes in the first 3 months while a gradual loss of RPE hints at a progressing decline of visual acuity. Additional research is required to understand how these accurate OCT predictions can be leveraged for a personalized therapy regimen.

Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.