Advances in management strategies for large and persistent macular hole: An update.

The standard of care to treat small- and medium-sized macular holes (<400 µm diameter) consists of a conventional transconjunctival sutureless pars plana vitrectomy followed by ILM peeling and endotamponade, mainly with gas or in some cases with silicone oil, resulting in closure rates of over 90% and good functional results. Large (>400 µm diameter), chronic and persistent macular holes remain a surgical challenge since closure rates and functional results decrease with larger macular hole diameters. Various modifications of the conventional surgical technique were introduced to improve anatomic and functional success in refractory cases not suitable for conventional macular hole surgery. These techniques comprise the positioning of tissue at the top of the hole to improve closure as performed by an inner limiting membrane flap and free flap preparation or the transplantation of autologous retinal tissue, lens capsule or amniotic membrane. For the treatment of very large and persistent macular holes, the induction of a localized retinal detachment at the posterior pole by subretinal injection of balanced salt solution and a subsequent attenuation of the rim of the hole during fluid-air exchange has been suggested as a promising surgical technique. In particular, accurate patient education about the expected surgical outcome in this specific group of patients appears important.

Natural History and Surgical Outcomes of Lamellar Macular Holes.

PURPOSE: To assess the natural history and surgical outcomes of lamellar macular holes (LMHs). DESIGN: Retrospective and consecutive case series. SUBJECTS: Patients with LMHs from multiple tertiary care centers. METHODS: Clinical charts and OCT scans were reviewed. MAIN OUTCOME MEASURES: The visual acuity (VA) changes and the occurrence rate of full-thickness macular hole (FTMH) were studied in both groups. Within the operated group, factors associated with 6-month VA and development of FTMH were explored. RESULTS: One hundred seventy-eight eyes were included, of which 89 were monitored and 89 underwent surgery. In the observation group, the mean VA decreased from 0.25 ± 0.18 to 0.28 ± 0.18 logarithm of the minimum angle of resolution (logMAR; P = 0.13), with 14 eyes (15.7%) that lost ≥ 0.2 logMAR VA, after 45.7 ± 33.3 months. Nine eyes (10.1%) spontaneously developed an FTMH. In the operated group, the mean VA increased from 0.47 ± 0.23 to 0.35 ± 0.25 logMAR at 6 months (P < 0.001) and 0.36 ± 0.28 logMAR (P = 0.001) after 24.1 ± 30.1 months. By multivariate analysis, better baseline VA (P < 0.001), the presence of an epiretinal membrane (P = 0.03), and the peeling of the internal limiting membrane (ILM; P = 0.02), with a greater effect of ILM perihole sparing, were associated with a greater 6-month VA. Perihole epiretinal proliferation sparing was associated with a better postoperative VA by univariate analysis (P = 0.03), but this was not significant by multivariate analysis. Eight eyes (9.0%) developed a postoperative FTMH. Using Cox proportional hazard ratios [HRs], pseudophakia at baseline (HR, 0.06; 95% confidence interval [CI], 0.00-0.75; P = 0.03) and peeling of the ILM (HR, 0.05; 95% CI, 0.01-0.39; P = 0.004) were protective factors, while ellipsoid zone disruption (HR, 10.5; 95% CI, 1.04-105; P = 0.05) was associated with an increased risk of FTMH. CONCLUSION: Observed eyes with LMH experienced, on average, progressive VA loss. Patients with LMH and altered vision may benefit from surgery. Internal limiting membrane peeling, with perihole ILM sparing, represents a crucial step of the surgery associated with a greater VA and a lower risk of postoperative FTMH. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

[Vitreous body in the treatment of exudative age-related macular degeneration : The medium is the message]. / Glaskörper bei der Therapie der exsudativen altersabhängigen Makuladegeneration : Das Medium ist die Message.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) is the standard treatment for exudative age-related macular degeneration (AMD). The constitution of the vitreomacular interface varies greatly in cases of attached (with or without traction) or detached vitreous body, which can impact the effectiveness of the anti-VEGF treatment. OBJECTIVE: Based on the current literature this article displays the current state of the science on whether the constitution of the vitreous body has an effect on the anti-VEGF treatment. MATERIAL AND METHODS: The published data extracted from current trials and post hoc analyses concerning this topic are presented and put into the clinical context. RESULTS: The presence of a vitreomacular adhesion reduces the efficacy of anti-VEGF treatment of exudative AMD. Posterior vitreous body detachment represents a positive prognostic factor concerning the efficacy of anti-VEGF treatment but not necessarily the prognosis for visual acuity. CONCLUSION: Patients with attached vitreous body need a more intensive treatment monitoring compared to patients with detached vitreous body. Therefore, in eyes with initial posterior vitreous body detachment receiving a treat and extend regimen, the interval between anti-VEGF injections can be extended to 4 instead of 2 weeks without endangering the success of treatment.

[Role of vitreous in the pathogenesis of neovascular age-related macular degeneration]. / Die Rolle des Glaskörpers in der Pathogenese der exsudativen altersabhängigen Makuladegeneration.

Age-related changes in vitreous molecular and anatomic morphology begin early in life and involve two major processes: vitreous liquefaction and weakening of vitreo-retinal adhesion. An imbalance in these two processes results in anomalous posterior vitreous detachment (PVD), which comprises, among other conditions, vitreo-macular adhesion (VMA) and traction (VMT). VMA is more common in patients with neovascular age-related macular degeneration (nAMD) than age-matched control patients, with the site of posterior vitreous adherence to the inner retina correlating with location of neovascular complexes. The pernicious effects of an attached posterior vitreous on age-related macular degeneration (AMD) progression involve mechanical forces, enhanced fluid influx and inflammation in and between the retinal layers, hypoxia leading to an accumulation of vascular endothelial growth factor (VEGF) and other stimulatory cytokines, and probably an infiltration of hyalocytes. It has been shown that vitrectomy not only mitigates progression to end-stage AMD, but existing choroidal neovascularization regresses after surgery. Thus, surgical PVD induction during vitrectomy or by pharmacologic vitreolysis may be considered in non-responders to anti-VEGF treatment with concomitant VMA.

[Vitreoretinal surgery in age-related macular degeneration]. / Vitreoretinale Chirurgie bei altersabhängiger Makuladegeneration.

The structure of the vitreous body, its interaction with the retinal surface and tractive alterations of the vitreoretinal interface may play a role in the pathogenesis and the development of age-related macular degeneration (AMD). From clinical trials it can be concluded that posterior vitreous detachment (PVD) or vitreous removal may protect against the development of neovascular AMD. Vitreomacular adhesions may promote neovascular AMD and may have an impact on the efficacy and frequency of intravitreal vascular endothelial growth factor (VEGF) inhibition. Therefore, vitreomacular surgery may be considered as a treatment option in selected cases. Peeling of epimacular membranes and the internal limiting membrane (ILM) may contribute to stabilizing visual acuity and reducing the treatment burden of current intravitreal pharmacotherapy. At present, surgical interventions in AMD are mainly performed in cases of submacular hemorrhage involving the fovea. The treatment is not standardized and consists of liquefaction of the blood using recombinant tissue plasminogen activator (rTPA) and its pneumatic displacement, potentially combined with VEGF inhibition. Other submacular surgical strategies, such as choroidal neovascularization (CNV) extraction, macular translocation or transplantation of retinal pigment epithelium (RPE) are currently limited to selected cases as a salvage treatment; however, the development of these submacular surgical interventions has formed the basis for new approaches in the treatment of dry and neovascular AMD including submacular or intravitreal gene and stem cell therapy.

[Disorders of the visual system following vitreoretinal and macular surgery]. / Störungen des visuellen Systems nach vitreoretinaler und makulärer Chirurgie.

The visual system is highly complex. Monocular or binocular disorders can develop, for example during tractive alterations of the macula, such as in epimacular membranes, and result in symptoms, such as double vision, aniseikonia or metamorphopsia. These symptoms are also observed following vitreomacular or vitreoretinal surgery, especially after treatment of large retinal detachment involving the macular area using pars plana vitrectomy or scleral buckle surgery but also as a result of vitreomacular interventions, such as membrane peeling in epimacular gliosis. Some patients have preoperatively existing latent conditions, which are not explicitly addressed during routine preoperative diagnostics. For patients and surgeons it is worth noting that these troublesome symptoms are often manifested in patients with good restoration of best corrected visual acuity following vitreomacular surgery. In such cases, patients tend to be dissatisfied with the surgical result despite good visual acuity. Treatment of postoperative metamorphopsia, aniseikonia and double vision is often difficult. In clinical studies, the maximum depth of tractive retinal folds has been described as a reliable morphological biomarker for the occurrence of metamorphopsia in epimacular gliosis. As metamorphopsia tends to postoperatively resolve slowly and even persist in ca. 30% of cases, this biomarker can have an impact on preoperative consulting and postoperative monitoring. Persistent binocular discomfort is often treatable by exact refraction correction and by applying a vertical and, if necessary, a horizontal prism. This often requires patience on the part of both the patient and the physician but is mostly successful due to fusion and adaptability.

[Visual acuity reduction and silicone oil tamponade]. / Visusminderung und Silikonöltamponade.

Silicone oil is an established intraocular surgical aid, which enables the treatment of the most complex starting situations but no other alternative has been found; however, the available data indicate that an unclear loss of visual acuity during or after an intraocular silicone oil tamponade possibly occurs more frequently than assumed from the clinical routine. Various pathological mechanisms are under discussion as causes, but the exact causes are actually unclear. In addition to atrophic alterations in the optical coherence tomography (OCT) examination, there are a clear reduction in visual acuity and mostly a central scotoma with otherwise inconspicuous findings. Unclear loss of visual acuity can also occur after removal of the silicone oil. Whether this is caused by the same pathological mechanism is unclear. Furthermore, there are no reproducible risk factors that appear a priori to possibly cause an unclear loss of vision under silicone oil; however, oil removal as soon as possible and a good adjustment of the intraocular pressure are recommended by the authors. Overall, a silicone oil tamponade should be carefully weighed up even when using modern highly purified silicone oils and it should therefore continue to be reserved particularly for unfavorable initial situations or complicated courses with the necessity for a silicone oil tamponade. Against this background, a study for systematic recording and processing of cases of unclear loss of visual acuity after silicone oil tamponade seems to be meaningful.

A model to quantify the influence of treatment patterns and optimize outcomes in nAMD.

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an 'optimal treatment' control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.

[Hordeolum and chalazion : (Differential) diagnosis and treatment]. / Hordeolum und Chalazion : (Differenzial­)Diagnose und Therapie.

Hordeolum and chalazion are the most frequent inflammatory eyelid tumors. They can occur in association with underlying diseases causing Meibomian gland dysfunction and/or chronic blepharitis. Due to the typical morphological features and clinical course, the diagnosis can mostly be clinically established. The majority of these lesions resolve spontaneously over time. In some instances, surgical intervention is unavoidable. In persistent, recurrent or clinically atypical cases malignant tumors must be excluded as a differential diagnosis by excisional biopsy and histopathological assessment.

[Macular detachment for treatment of large, persistent and chronic macular holes]. / Makulaabhebung zur Therapie des großen, persistierenden und chronischen Makulaloches.

Large, persistent or chronic macular holes still represent a surgical challenge, which can be addressed using the presented surgical technique. A subretinal injection of balanced salt solution (BSS) at the posterior pole of the macular region is performed during transconjunctival pars plana vitrectomy in order to induce an elevation of the neurosensory retina in the macular region. The hole is then attenuated during fluid-air exchange, followed by a gas or silicone oil tamponade. The presented technique appears to be useful for large and persistent macular holes, which are not suitable for conventional macular hole surgery. The exact patient information on the potential outcome of surgery in this specific group of patients seems particularly important.

[Clinical Decision Making for Treatment of Diabetic Macular Oedema with DEX Implant: a Consensus Paper]. / Klinische Entscheidungsfindung bei der Behandlung des diabetischen Makulaödems mit DEX-Implantat: ein Konsenspapier.

BACKGROUND: Currently two intravitreally applied corticosteroids (dexamethasone and fluocinolone) are licensed in Germany for treatment of diabetic macular oedema (DME). The use of DEX implant for DME in daily clinical practice has not been defined in detail. Following a Delphi panel survey, a group of retina experts set out to come up with a consensus for use of the DEX implant in DME. MATERIAL AND METHODS: International and national treatment recommendations were identified from the literature. A steering group generated a catalogue of 72 statements on the aetiology and pathogenesis of DME, therapy with DEX implant, use of DEX implant in patients previously treated with VEGF-inhibitors, use of DEX implant in combination therapy, safety of DME therapies as well as patients' burden of treatment. Twenty-two ophthalmologists from private practice and 6 hospital ophthalmologists participated in the Delphi panel via Survey Monkey. Consensus was reached if at least 75% of participants agreed or disagreed with a statement. Statements for which consensus was not reached were discussed once more during the expert consensus meeting and a vote was taken. Based on these results a treatment algorithm for foveal DME was proposed. RESULTS: If a patient does not show sufficient response after 3 - 6 months of anti-VEGF treatment (visual acuity gain of < 5 ETDRS letters or reduction of central retinal thickness ≤ 20%), a switch to DEX implant should take place. DEX implant is also suitable in eyes with longer presentation of DME, showing e.g. massive lipid exudates. DEX implant is suitable as first-line therapy especially in pseudophakic patients, patients unwilling or able to comply with tight anti-VEGF injection intervals or patients with known vascular diseases. With fixed control visits every 4 - 8 weeks, use of DEX implant is flexible and individual. Decision parameters for repeated use should be visual acuity, retinal thickness and intraocular pressure. Treatment of both eyes on the same day should not take place. CONCLUSION: The algorithm presented reflects survey as well as expert discussion results and may differ from recommendations issued by the German professional society. The consensus recommendations for the treatment of DME generated during the survey and meeting of retina experts are intended to guide use of DEX implant in daily practice.

Application of subretinal fluid to close refractory full thickness macular holes: treatment strategies and primary outcome: APOSTEL study.

INTRODUCTION: Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. METHODS: Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. RESULTS: The mean duration of the MH prior to SR-fluid application was 17 months (6-96 months). The mean age of the patients at the time of surgery was 72 years (54-88). The mean preoperative aperture diameter of the opening was 1212 µm (239-4344 µm), base diameter 649 µm (SD 320 µm). The mean preoperative BCVA prior to surgery was 0.1 (0.01-0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02-0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. CONCLUSION: Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.

Current concepts of pharmacotherapy of diabetic macular edema.

Introduction: Diabetic macular edema (DME) is a sight threatening disease and a major cause for blindness for people in working age. The pathogenesis is multifactorial and complex. The pharmacotherapy of DME addresses both the inhibition of vascular endothelial growth factor (VEGF) by the intravitreal injection of VEGF inhibitors and inflammatory processes by the intravitreal application of steroids. Several trials have been published reporting on the efficacy and safety of these treatments.Areas covered: This review discusses original research articles including basic science and clinical studies as well as review articles focusing on the role of inflammation and VEGF expression in DME. It discusses newly published clinical trials on intravitreal pharmacotherapy for DME. The literature was searched using Medline/PubMed and was selected given its relevance for the topic to be discussed.Expert opinion: Our knowledge regarding the pathophysiology of diabetic macular edema has significantly increased. Some of these insights have been successfully transferred into current treatment strategies already including VEGF suppression or anti-inflammatory treatments using steroids. The identification of additional pathophysiological aspects and their relevance as potential treatment targets will be a future challenge in the treatment of DME. A better knowledge on the complex pathophysiology will also help to establish combination strategies.

[Surgery of large and persistent macular holes]. / Chirurgie des großen und persistierenden Makulaforamens.

Modern macular hole surgery results in high closure rates of over 90% and good functional results especially in macular holes up to 400 µm in diameter. The standard of care in most of these cases consists of transconjunctival sutureless pars plana vitrectomy, peeling of the inner limiting membrane (ILM) around the hole, followed by gas tamponade and positioning of the patient. As closure rates and functional results decrease with larger macular hole diameters over approximately 400 µm, alternative surgical techniques have been introduced to improve anatomical and functional results in these cases. These techniques include the positioning of tissue within the macular hole to improve hole closure. This can be performed using an ILM flap or free flap technique and the transplantation of autologous retinal tissue, lens capsule or homologous amniotic tissue in or under the defect. An alternative promising approach is the attenuation of the rim of the hole by induction of a localized retinal detachment at the posterior pole which is achieved by subretinal injection of balanced salt solution (BSS) using a 41 gauge needle. The operation is completed by an endotamponade using gas or silicone oil.

Lamellar macular hole surgery - current concepts, future prospects.

Lamellar macular holes present distinct morphological features including tractional or non-tractional epimacular membranes, foveal tissue alterations, defects of the outer retinal layers, or a separation of the retinal layers. At present, degenerative lamellar holes are differentiated from tractional holes based on the morphological characteristics seen in OCT. The current treatment approach is based on this gross differentiation. Considering the recent developments in high-resolution imaging, this classification needs to be revisited since morphological features may present simultaneously, making it difficult to separate these entities. In addition, a revisited classification may be of value to better standardize the indication for surgical treatment.

[Vitreomacular Traction Following Anti-VEGF Therapy - Two Cases]. / Vitreomakuläres Traktionssyndrom im Rahmen der Anti-VEGF-Therapie ­ 2 Kasuistiken.

Vitreomacular traction syndrome (VMTS) is defined as an incomplete or anomalous posterior vitreous detachment resulting in tractional forces at the macular region. In the context of anti-VEGF therapy, the formation of vitreoretinal traction has mainly been reported as a potential complication of VEGF inhibition in ischemic proliferative retinal disease, such as proliferative diabetic retinopathy. In this report, we present two patients who developed VMTS during anti-VEGF therapy for exudative age-related macular degeneration and diabetic macular edema. VMTS following anti-VEGF therapy of exudative macular diseases is rare. The exact pathomechanism remains unclear. However, there is a hypothesis that in eyes with adherent vitreous cortex, the induction of fibrosis as a result of the VEGF inhibition may lead to vitreomacular traction.

[Cost Comparison of Licensed Intravitreal Therapies for Insufficiently Anti-VEGF Responding Fovea Involving Diabetic Macular Edema in Germany]. / Kostenvergleich zugelassener intravitrealer Therapien bei nicht ausreichend auf primäre Therapie ansprechendem diabetischem Makulaödem mit fovealer Beteiligung in Deutschland.

BACKGROUND: In the treatment of center-involving diabetic macular edema, despite initial therapy with an anti-VEGF compound, an insufficient response may occur. Further therapy options include a switch of anti-VEGF products or to corticosteroid implants, such as Fluocinolone acetonide or Dexamethasone. OBJECTIVES: Firstly, to investigate systematically which evidence-based study data are available describing the efficacy of in-label treatments after primary anti-VEGF treatment, secondly, to investigate which costs go along for the healthcare provider. METHODS: A systematic literature review (SLR) for randomized controlled trials (RCT) was performed in Medline and Embase. A short-term cost-cost model was built in MS Excel with a 3 year time horizon to compare in-label intravitreal options Ranibizumab (Lucentis®), Aflibercept (Eylea®), Fluocinolone acetonide implant (Iluvien®), and Dexamethasone implant (Ozurdex®). Cost components comprised of drug and injection costs, optical coherence tomography (OCT) procedures, and adverse events such as endophthalmitis, IOP-lowering drugs and surgery and cataract surgery. RESULTS: A total of 42 publications of 20 RCTs were identified. No study had a clearly defined population after first line anti-VEGF treatment, thus no direct efficacy comparison was possible. In the short-term cost-cost model total costs were 17,542 € for Ranibizumab, 15,896 € for Aflibercept, 10,826 € for Fluocinolone acetonide implant and 12,365 € for Dexamethasone implant. For all treatment regimens, drug costs were the predominant cost component, followed by injection costs (with variations dependent on the specific drug) and OCT costs. In the uni- and multivariate sensitivity analyses, the results obtained were robust to changes of model inputs. CONCLUSIONS: In summary, the short-term cost-cost comparison demonstrates that steroid implants can provide significant cost savings versus in-label anti-VEGF treatment for center-involving diabetic macular edema. Single application of the long-lasting Fluocinolone acetonide implant is the most cost-efficient in-label treatment option.

Vitrectomy for Diabetic Macular Edema: Optical Coherence Tomography Criteria and Pathology of the Vitreomacular Interface.

PURPOSE: To correlate spectral-domain optical coherence tomography (SDOCT) criteria and clinical data with pathology of the vitreomacular interface (VMI) in eyes with diabetic macular edema (DME). DESIGN: Retrospective cross-sectional study and laboratory investigation. METHODS: We included specimens of 27 eyes of 26 patients with center-involved DME that underwent vitrectomy with peeling of the internal limiting membrane (ILM). Selection of specimens was consecutive and in retrospect using our register of the Vitreoretinal Pathology Unit. Clinical data and SDOCT examinations were correlated to immunocytochemistry and transmission electron microscopy. Classification of DME comprised sponge-like diffuse retinal thickening, cystoid macular edema, and serous retinal detachment. VMI was evaluated for presence of epiretinal membrane (ERM) and thickened vitreous cortex (tVC). RESULTS: ERMs and tVC were found in all DME types. Diffuse DME showed tVC more often than cystoid DME. Hyalocytes, contractile myofibroblasts, glial cells, matrix metalloproteinases-2 and -9, and collagen type I, II, and III were positive tested irrespective of DME type. There were no significant cell fragments at the retinal side of the ILM. Visual acuity improved in the majority of cases and macular thickness decreased significantly during mean follow-up of 17 ± 10 months. CONCLUSIONS: All eyes presented pathologic VMI changes irrespective of the OCT classification of DME type or presence of ERM. Composition of fibrocellular membranes at the VMI indicated remodeling of vitreous cortex and transdifferentiation of hyalocytes into myofibroblasts. Our findings might argue for an early surgical intervention in eyes with DME irrespective of the presence of traction formation imaged by SDOCT.