Publications by authors named "Carsten H Meyer"

181 Publications

External limiting membrane: retinal structural barrier in diabetic macular edema.

Int J Retina Vitreous 2021 Mar 4;7(1):16. Epub 2021 Mar 4.

Macula Center Graubunden, Davos and Triemli Spital, Zurich, Switzerland.

Advances in spectral-domain optical coherence tomography (SD-OCT) technology have enhanced the understanding of external limiting membrane (ELM) and ellipsoid zone (EZ) in diabetic macular edema. An increase in VEGF has been demonstrated to be associated with sequential ELM and EZ disruption on SD-OCT. An intact ELM is a prerequisite for an intact EZ in DME. Anti-VEGF therapy leads to restoration of barrier effect of ELM. The ELM restores first followed by EZ restoration.
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http://dx.doi.org/10.1186/s40942-021-00284-xDOI Listing
March 2021

Macular microhole and foveal red spot syndrome: a critical review of the literature.

Graefes Arch Clin Exp Ophthalmol 2020 Nov 2. Epub 2020 Nov 2.

Department of Ophthalmology, Saint Louis University School of Medicine, St. Louis, MO, USA.

Purpose: The purpose of this article is to review the literature on nomenclature, natural history, clinical features, diagnosis, management, and prognosis of both macular microhole (MMH) and foveal red spot syndrome (FRS).

Methods: A PubMed primary literature search (February 1, 2020) utilizing the terms macular microhole, foveal red spot syndrome, and outer retinal hole was conducted. All chosen articles were case reports or case series. Articles qualified for inclusion if they documented symptoms, imaging findings, or followed patients longitudinally.

Results: A total of 14 studies from 1988 to 2019 that evaluated either MMH, FRS, or both were included in the review. No comparative study between the two defects was found. Studies often used the terms FRS and MMH interchangeably to reference both partial- and full-thickness lesions of the macula. Spectral-domain optical coherence tomography (SD-OCT) was most frequently able to identify these lesions and revealed an absence of all neural retinal layers from the inner limiting membrane (ILM) to the retinal pigment epithelium (RPE) in the full-thickness lesions while the partial-thickness lesions most often involved the photoreceptor layer (PRL) and less frequently the external limiting membrane (ELM). OCT revealed that vitreomacular traction (VMT) was involved in the natural history of both FRS and MMH for a significant subset of patients.

Conclusion: The terms MMH and FRS have been used interchangeably in the literature. Advances in OCT have revealed that MMHs and FRSs are distinct but sometimes overlapping entities. We suggest that MMH and FRS are similar entities defined as one or more sharply defined lesions in the fovea of the eye < 150 μm in size. MMHs are a full-thickness defect of the entire neuroretina at the center of the foveola while FRSs are partial-thickness lesions. Current literature suggests that there may be subtle differences in the pathogenesis, clinical features, and diagnosis between MMH and FRS; however, prognosis and management for both are favorable. Lastly, we suggest that the terms outer lamellar macular microholes and full-thickness macular microholes may be the more appropriate terminologies to refer to FRS and MMH, respectively.
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http://dx.doi.org/10.1007/s00417-020-04995-zDOI Listing
November 2020

[50 Years Pars-plana Vitrectomy: the Driving Force Derived from Germany].

Authors:
Carsten H Meyer

Klin Monbl Augenheilkd 2020 Sep 23;237(9):1041-1042. Epub 2020 Sep 23.

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http://dx.doi.org/10.1055/a-1218-6606DOI Listing
September 2020

Sequential restoration of external limiting membrane and ellipsoid zone after intravitreal anti-VEGF therapy in diabetic macular oedema.

Eye (Lond) 2020 Jul 20. Epub 2020 Jul 20.

Vitreoretinal and Uveitis Service, Department of Ophthalmology, St. Louis University School of Medicine, St. Louis, MO, USA.

Background/objectives: To study the mechanism of restoration of retinal photoreceptor ellipsoid zone (EZ), after intravitreal bevacizumab (IVB) therapy, in diabetic macular oedema (DMO).

Subjects/methods: Forty-four consecutive patients aged 40-65 years having type 2 diabetes mellitus (DM) with DMO were prospectively recruited for IVB therapy. It comprised of three doses (1.25 mg in 0.05 ml) of IVB at monthly intervals. Patients with other ocular and systemic diseases affecting retinal vessels and earlier ophthalmological interventions were excluded. Visual acuity (logMAR VA) was recorded. Spectral domain optical coherence tomography (SD-OCT) was performed pre and post intervention. Central sub-foveal thickness (CST) and grades of disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) and EZ were assessed. Data were statistically analysed on SPSS software. Clinical trials registry: CTRI/2019/03/018135.

Results: Mean logMAR VA decreased after IVB therapy from 1.78 ± 0.07 pre-intervention to 0.42 ± 0.05 post intervention (p < 0.001). Similarly, CST reduced from 354.23 ± 15.0 µm pre-intervention to 233.18 ± 7.88 µm post intervention (p < 0.001). Among qualitative variables, DRIL decreased from 93.2% pre-intervention to 13.6% post intervention. Likewise, global ELM disruption reduced from 81.8 to 9.1% and global EZ disruption reduced from 79.5 to 11.4%. ELM restoration preceded EZ restoration.

Conclusion: Anti-VEGF therapy restores the barrier effect of ELM. It causes ELM to restore first followed by EZ restoration in DMO.
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http://dx.doi.org/10.1038/s41433-020-1100-0DOI Listing
July 2020

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

Graefes Arch Clin Exp Ophthalmol 2020 Oct 24;258(10):2151-2161. Epub 2020 Jun 24.

Department of Ophthalmology, Herzog Carl Theodor Eye Clinic, Munich, Germany.

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.
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http://dx.doi.org/10.1007/s00417-020-04735-3DOI Listing
October 2020

Critical analysis of techniques and materials used in devices, syringes, and needles used for intravitreal injections.

Prog Retin Eye Res 2021 Jan 18;80:100862. Epub 2020 Apr 18.

Department of Ophthalmology, Federal University of São Paulo, Rua Botucatu, 806, São Paulo, SP, Brazil; Department of Ophthalmology, SSM Health Saint Louis University Hospital, Saint Louis University, 1755, S. Grand Boulevard, Saint Louis, MO, USA.

Intravitreal injections have become the most commonly performed intraocular treatments worldwide. Because intravitreal injections may induce severe adverse events, such as infectious and noninfectious endophthalmitis, cataract, ocular hypertension, vitreous hemorrhage, or retinal detachment, appropriate awareness of the materials and techniques used are essential to reduce these sight-threatening complications. This review provides insights into the needles, syringes, silicone oil coating, sterilization methods, devices to assist intravitreal injections, scleral piercing techniques using needles, syringe handling, anesthesia, and safety issues related to materials and techniques. It is paramount that physicians be aware of every step involved in intravitreal injections and consider the roles and implications of all materials and techniques used. The ability to understand the theoretical and practical circumstances may definitely lead to state-of-the-art treatments delivered to patients. The most important practical recommendations are: choosing syringes with as little silicone oil as possible, or, preferably, none; avoiding agitation of syringes; awareness that most biologics (e.g., antiangiogenic proteins) are susceptible to changes in molecular properties under some conditions, such as agitation and temperature variation; understanding that improper materials and techniques may lead to complications after intravitreal injections, e.g., inflammation; and recognizing that some devices may contribute to an enhanced, safer, and faster intravitreal injection technique.
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http://dx.doi.org/10.1016/j.preteyeres.2020.100862DOI Listing
January 2021

[Closure of Persisting Full Thickness Macular Holes by Subretinal Fluid Application: Technical Approach and Surgical Considerations].

Klin Monbl Augenheilkd 2021 Feb 14;238(2):173-178. Epub 2020 Apr 14.

Augenzentrum Nymphenburger Höfe, München.

Introduction: Firm adhesions between the retina and adjacent retinal pigment epithelium (RPE) may prevent the closure of macular holes (MH) after chromovitrectomy. Controlled application of subretinal (SR) fluid with BSS may release these adhesions leading to closure of the retracted retina in large and or refractory macular holes.

Methods: For a standardized procedure, it is recommended to exclude residues of epiretinal membranes on the retinal surface preoperatively at OCT or intraoperatively by means of vital dyes. Intraoperatively, a perfluorocarbon (PFO) bubble is placed above the MH and lowers the infusion bottle of 20 mmHg. Subsequently, SR-fluid blebs are applied in the upper, temporal and inferior quadrants with a subretinal 41-gauge cannula. After removing decalin bubble, the SR-detachment is enlarged toward the foveal center. This is essential to achieve a complete detachment of the outer macular edges from the RPE. The MH can be closed by a temporary gas endotamponade.

Results: With a standardized procedure, the operation can be carried out safely and with minimal effort. Additional measures, such as care for bubble-free SR-fluid sands or machine assistance, were added. In a pilot study, experienced VR surgeons performed the SR-fluid application safely and without complications. The preoperative diameter of the MH was 1150 µm (651 - 2350 µm). The secondary closure rate for our PMH was 80.9%.

Conclusion: SR-adhesions seem to have a previously unnoticed component in persistent macular holes. An SR-fluid application can be carried out quickly, safely and with minimal material effort. The initial results show a high secondary closure rate.
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http://dx.doi.org/10.1055/a-1120-8673DOI Listing
February 2021

Serum vitamin D is a biomolecular biomarker for proliferative diabetic retinopathy.

Int J Retina Vitreous 2019 5;5:31. Epub 2019 Nov 5.

Department of Ophthalmology, Pallas Klinik, Aarau, Switzerland.

Background: Vitamin D is a multi-functional fat-soluble metabolite essential for a vast number of physiological processes. Non-classical functions are gaining attention because of the close association of vitamin D deficiency with diabetes, and its complications. The present study was undertaken to evaluate the role of vitamin D as a biomarker for proliferative diabetic retinopathy.

Methods: A tertiary care center based cross-sectional study was undertaken. Seventy-two consecutive cases of type 2 diabetes mellitus were included. Diagnosis of diabetes mellitus was made using American Diabetes Association guidelines. Study subjects included: diabetes mellitus with no retinopathy (No DR) (n = 24); non-proliferative diabetic retinopathy (n = 24); and proliferative diabetic retinopathy (n = 24) and healthy controls (n = 24). All of the study subjects underwent complete ophthalmological evaluation. Best Corrected Visual Acuity (BCVA) was measured on the logarithm of the minimum angle of resolution (logMAR) scale. Serum 25-OH Vitamin D assay was done using chemiluminescent microparticle immunoassay technology. Diagnostic accuracy of vitamin D was assessed using receiver operating characteristics curve analysis and area under curve (AUC) was determined for the first time.

Results: ANOVA revealed a significant decrease in serum vitamin D levels with severity of diabetic retinopathy (F = 8.95,  < 0.001). LogMAR BCVA was found to increase significantly with the severity of DR (F = 112.64,  < 0.001). On AUC analysis, a cut off value of 18.6 ng/mL for Vitamin D was found to be significantly associated with proliferative diabetic retinopathy [sensitivity = 86.36% (95% CI 65.1-96.9); specificity = 81.82% (95% CI 59.7-94.7); AUC = 0.91 (excellent); and Z value = 8.17].

Conclusions: Serum vitamin D levels of ≤ 18.6 ng/mL serve as sensitive and specific indicator for proliferative disease, among patients of DR.
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http://dx.doi.org/10.1186/s40942-019-0181-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829921PMC
November 2019

Serum vascular endothelial growth factor is a biomolecular biomarker of severity of diabetic retinopathy.

Int J Retina Vitreous 2019 1;5:29. Epub 2019 Oct 1.

5Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India.

Background: Elevated serum vascular endothelial growth factor (VEGF) levels are associated with diabetic retinopathy (DR). Serum VEGF levels correlate with vitreous levels. Neuroretinal changes occur even before the appearance of vascular signs in DR. Role of VEGF as a biomarker for DR has not been assessed. Serum VEGF as a biomarker for severity of DR, was evaluated for the first time.

Methods: Consecutive cases of type 2 diabetes mellitus [without DR, (no DR, n = 38); non-proliferative DR, (NPDR, n = 38); proliferative DR, (PDR, n = 40)] and healthy controls (n = 40) were included. Serum VEGF was measured using enzyme linked immunosorbent assay. Accuracy of VEGF as a biomarker for severity of retinopathy was measured using the area under the receiver operator characteristic (ROC) curve.

Results: Serum VEGF levels in controls, No DR, NPDR and PDR groups showed significant incremental trend from 138.96 ± 63.37 pg/ml (controls) to 457.18 ± 165.69 pg/ml (PDR) (F = 48.47;  < 0.001). Serum VEGF levels were observed to be significantly elevated even before DR had set in clinically. ROC for serum VEGF levels was significant in discriminating between the cases and the controls and had good accuracy in discerning between subjects with and without retinopathy. The area under curve (AUC ± SE) for discrimination was significant: (a) cases and controls (n = 156): AUC = 0.858 ± 0.029,  < 0.001; (b) DR (NPDR + PDR) and No DR (n = 116): AUC = 0.791 ± 0.044,  < 0.001; and (c) NPDR and PDR (n = 78): AUC = 0.761 ± 0.056,  < 0.001, with over 90% projected sensitivity and specificity at various cut off values.

Conclusion: Serum VEGF level is a simple, effective laboratory investigative test in predicting the onset of DR in eyes showing no evidence of DR and serves as a reliable biomolecular biomarker for severity of DR.
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http://dx.doi.org/10.1186/s40942-019-0179-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771093PMC
October 2019

Anterior chamber paracentesis during intravitreal injections in observational trials: effectiveness and safety and effects.

Int J Retina Vitreous 2019 6;5. Epub 2019 Mar 6.

9Bascom Palmer Eye Institute, University of Miami, Miami, FL USA.

A paracentesis prior to an intravitreal injection is a very safe procedure and can prevent IOP-spikes after injections. As these spikes pose the risk of inducing glaucomatous changes particularly in patients with frequent injections and/or with a risk profile, a regular paracentesis prior to an injection may be considered and discussed with the patient.
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http://dx.doi.org/10.1186/s40942-019-0157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402161PMC
March 2019

Central subfield thickness and cube average thickness as bioimaging biomarkers for ellipsoid zone disruption in diabetic retinopathy.

Int J Retina Vitreous 2018 2;4:41. Epub 2018 Nov 2.

4Department of Ophthalmology, Saint Louis University, St. Louis, USA.

Background: To evaluate the association of central subfield thickness (CST) and cube average thickness (CAT) with ellipsoid zone (EZ) disruption on spectral domain optical coherence tomography (SD-OCT) in patients of diabetic retinopathy (DR).

Methods: Cross sectional study including consecutive patients of type 2 diabetes mellitus [without DR (No DR, n = 97); non-proliferative DR (NPDR, n = 91); proliferative DR (PDR, n = 83)] and healthy controls (n = 82) was undertaken. CST and CAT values were measured using SD-OCT. Data was analyzed using Chi square test, ANOVA and multivariate analysis. Discriminant values of CST and CAT for EZ disruption were evaluated using receiver operator characteristic curve. Area under curve (AUC) was computed.

Results: Mean CAT and CST values in the study subjects showed an incremental trend. Multivariate ordinal logistic regression analysis showed increase in CST (OR = 1.022, p < 0.001) and CAT (OR = 1.029, p < 0.001) as significant independent predictors of EZ disruption. Area under curve showed excellent predictive results of CST (AUC = 0. 943 ± 0.021, 95% CI, 0.902-0.984, p < 0.05) and CAT (AUC = 0.959 ± 0.012, 95% CI 0.936-0.982, p < 0.05), as bioimaging biomarkers, for EZ disruption.

Conclusion: Increase in CST and CAT is associated with increased odds of EZ disruption and these macular parameters serve as bioimaging biomarkers for EZ disruption in DR.
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http://dx.doi.org/10.1186/s40942-018-0144-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214155PMC
November 2018

Evaluation of aflibercept and ziv-aflibercept binding affinity to vascular endothelial growth factor, stability and sterility after compounding.

Int J Retina Vitreous 2018 24;4:39. Epub 2018 Oct 24.

4Vision Institute, Department of Ophthalmology, Federal University of São Paulo, São Paulo, SP Brazil.

Purpose: To investigate the binding affinity, stability, and sterility of aflibercept and ziv-aflibercept to vascular endothelial growth factor (Holash et al. in Proc Natl Acad Sci USA 99(17):11393-11398, 2002. 10.1073/pnas.172398299) after compounding and storage for up to 28 days at 4 °C and - 8 °C.

Methods: Tuberculin-type 1-mL syringes were prepared containing aflibercept (40 mg/mL) and ziv-aflibercept (25 mg/mL). Samples were stored at 4 °C and - 8 °C for 0, 14, and 28 days and evaluated for the binding affinity of anti-VEGF to VEGF and stability using enzyme-linked immunosorbent assays. The evaluation of sample sterility was performed.

Results: Laboratory trials with aflibercept and ziv-aflibercept showed preservation of the drug-binding capability to recombinant VEGF when stored in plastic syringes for up to 28 days at 4 °C and - 8 °C. No significant decrease in mass or concentration were observed. Microbiologic evaluations did not detect contamination in the syringes.

Conclusions: The current study corroborates that compounded anti-VEGF drugs aflibercept and ziv-aflibercept do not loose stability or binding affinity and do not become contaminated if prepared under sterile conditions and stored at 4 °C or - 8 °C for 14 or 28 days.
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http://dx.doi.org/10.1186/s40942-018-0143-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199727PMC
October 2018

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes.

Ophthalmic Surg Lasers Imaging Retina 2018 04;49(4):245-250

Background And Objective: To study the safety and efficacy of intravitreal injections of ziv-aflibercept (IVI-ZA) (Zaltrap; Sanofi-Aventis and Regeneron Pharmaceuticals, Tarrytown, NY) during a period of 48 weeks in patients with diabetic macular edema (DME).

Patients And Methods: Seven consecutive patients with DME were enrolled and submitted to 12 consecutive IVI-ZA with a 4-week interval. The safety parameters included changes in full-field electroretinogram (ERG) and systemic or ocular complications, and the efficacy parameters were the mean change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT).

Results: No significant differences were found in any ERG component after IVI-ZA, and no systemic or ocular complication was observed. The improvement of BCVA was most significant after the first IVI-ZA and remained until week 48 (P < .05). The CRT significantly decreased during the course of 48 weeks.

Conclusion: The 48-week results are consistent with our previous 24-week findings, supporting IVI-ZA as a safe, efficient, and well-tolerated therapy for patients with DME. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:245-250.].
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http://dx.doi.org/10.3928/23258160-20180329-06DOI Listing
April 2018

Resistive index of ophthalmic artery correlates with retinal pigment epithelial alterations on spectral domain optical coherence tomography in diabetic retinopathy.

Int J Retina Vitreous 2018 9;4:12. Epub 2018 Apr 9.

Department of Ophthalmology, Pallas Klinik, Aarau, Switzerland.

Background: Retinal pigment epithelium (RPE) plays a significant role in maintenance of integrity of retinal photoreceptors and choriocapillaries. RPE derives its blood supply through ophthalmic artery (OA) via choriocapillaries. RPE topographic alterations have been observed to be associated with severity of retinopathy. The present study was undertaken to assess the correlation between resistive index (RI) of the OA with RPE topographic alterations on Spectral-Domain optical coherence tomography (SD-OCT), to our knowledge, it is for the first time.

Methods: A tertiary care center based cross-sectional study was undertaken after informed consent. Sample size was calculated using 95% confidence interval. Seventy five consecutive cases of type 2 diabetes mellitus between the ages of 40 and 70 years were included. The cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study classification: diabetes mellitus with no retinopathy (No DR) (n = 24); non-proliferative diabetic retinopathy (n = 27); and proliferative diabetic retinopathy (n = 24). Healthy control subjects of similar age group were included (n = 24). RI in OA was studied using Color Doppler imaging. Grades of RPE topographic alterations and retinal photoreceptor ellipsoid zone (EZ) disruption were studied using SD-OCT. Data was analysed using Chi square (χ) test, analysis of variance (ANOVA), Pearson correlation analysis and Neuman-Keuls test.

Results: LogMAR best corrected visual acuity was found to increase significantly with the severity of DR (F = 105.74,  < 0.001). ANOVA revealed a significant increase in RI of OA (F = 14.23,  < 0.001) with severity of diabetic retinopathy. χ test revealed significant increase in grades of RPE alterations (χ = 71.83,  < 0.001) and EZ disruption (χ = 60.59,  < 0.001) with the severity of diabetic retinopathy. Pearson correlation analyses revealed a significant positive correlation between RI of OA with grades of RPE alterations (r = 0.48,  < 0.001) and also between grades of RPE alterations and EZ disruption (r = 0.82,  < 0.001).

Conclusions: Decrease in ocular blood flow resulting from an increase in RI of OA correlates with severity of DR and grades of topographic alterations in RPE. Integrity of EZ was observed to be dependent on RPE.
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http://dx.doi.org/10.1186/s40942-018-0116-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890348PMC
April 2018

Subretinal fluid application to close a refractory full thickness macular hole.

Int J Retina Vitreous 2017 27;3:44. Epub 2017 Nov 27.

Pallas Clinics, Bahnhofplatz 2, 5000 Aarau, Switzerland.

Background: To close a refractory full thickness macular hole (FTMH) by adjacent subretinal fluid application to release the elastic retina from the retinal pigment epithelium (RPE).

Case Presentation: A 83 years old patient presented an old FTMH with a diameter of 1444 μm. After confirming intraoperatively the complete release of the epiretinal membrane around the FTMH, we installed 3 small subretinal blebs around the hole, to release the adjacent retina from the RPE. The mobilized retina was gently moved towards the macular center. A silicone oil tamponade was installed to secure a proper healing and observation of the FTMH. The closure of the 1444 μm FTMH was seen on indirect ophthalmoscopy and confirmed by OCT 5 days after surgery by restoring the retinal architecture. A late reopening was not apparent at the postoperative observations. Visual acuity improved from hand motion to 20/200 at 4 weeks postoperative.

Conclusion: Although FTMH develop by epiretinal tangential traction, large FTMH may persist even after complete release of its epiretinal traction. Subretinal fluid application may release the flexible retina from the RPE to achieve a relocation at the central fovea facilitating an anatomical closure of the macular hole.
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http://dx.doi.org/10.1186/s40942-017-0094-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702967PMC
November 2017

[Laser Iridotomy - In Cases of Acute Angle Closure Only?]

Klin Monbl Augenheilkd 2017 Nov 3;234(11):1372-1377. Epub 2017 May 3.

Augenklinik, Universität Bonn.

The narrowing of the chamber angle-as a result of anatomic predispositions like high hyperopia or increasing lens thickness-poses the greatest risk for acute angle closure. A laser iridotomy counts as a standard procedure in cases of acute angle closure, whereas there are no coherent recommendations or guidelines for a prophylactic therapy. Modern imaging techniques, such as anterior segment optical coherence tomography or Scheimpflug photography, can give valuable information for the planning of treatment. This review presents traditional and modern imaging techniques and summarises recommendations for action in relation to recent publications.
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http://dx.doi.org/10.1055/s-0043-105272DOI Listing
November 2017

INCREASED SERUM LEVELS OF UREA AND CREATININE ARE SURROGATE MARKERS FOR DISRUPTION OF RETINAL PHOTORECEPTOR EXTERNAL LIMITING MEMBRANE AND INNER SEGMENT ELLIPSOID ZONE IN TYPE 2 DIABETES MELLITUS.

Retina 2017 Feb;37(2):344-349

*Retina Service, Department of Ophthalmology, King George's Medical University, Lucknow, India;Departments of †Social and Preventive Medicine, and‡Pathology, King George's Medical University, Lucknow, India;§Department of Ophthalmology, Pallas Klinik, Olten, Switzerland;¶Department of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia;**Department of Cardiovascular Diseases, International Clinical Research Center, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic; and††Department of Ophthalmology, Saint Louis University Eye Institute, Saint Louis University, St. Louis, Missouri.

Purpose: To evaluate the role of serum urea and creatinine as surrogate markers for disruption of retinal photoreceptor external limiting membrane (ELM) and inner segment ellipsoid zone (EZ) in Type 2 diabetic retinopathy (DR) using spectral-domain optical coherence tomography, for the first time.

Methods: One hundred and seventeen consecutive cases of Type 2 diabetes mellitus (diabetes without retinopathy [No DR; n = 39], nonproliferative diabetic retinopathy [NPDR; n = 39], proliferative diabetic retinopathy [PDR; n = 39]) and 40 healthy control subjects were included. Serum levels of urea and creatinine were assessed using standard protocol. Spectral-domain optical coherence tomography was used to grade the disruption of ELM and EZ as follows: Grade 0, no disruption of ELM and EZ; Grade 1, ELM disrupted, EZ intact; Grade 2, ELM and EZ disrupted. Data were analyzed statistically.

Results: Increase in serum levels of urea (F = 22.93) and creatinine (F = 15.82) and increased grades of disruption of ELM and EZ (γ = 116.3) were observed with increased severity of DR (P < 0.001). Increase in serum levels of urea (F = 10.45) and creatinine (F = 6.89) was observed with increased grades of disruption of ELM and EZ (P = 0.001).

Conclusion: Serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor ELM and EZ on spectral-domain optical coherence tomography in DR.
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http://dx.doi.org/10.1097/IAE.0000000000001163DOI Listing
February 2017

The potential of spectral domain optical coherence tomography imaging based retinal biomarkers.

Int J Retina Vitreous 2017 9;3. Epub 2017 Jan 9.

Harvard Medical School, Massachusetts Eye and Ear, Boston, MA USA.

Background: Biomarker", a merged word of "biological marker", refers to a broad subcategory of medical signs that objectively indicate the state of health, and well-being of an individual. Biomarkers hold great promise for personalized medicine as information gained from diagnostic or progression markers can be used to tailor treatment to the individual for highly effective intervention in the disease process. Optical coherence tomography (OCT) has proved useful in identifying various biomarkers in ocular and systemic diseases.

Main Body: Spectral domain optical coherence tomography imaging-based biomarkers provide a valuable tool for detecting the earlier stages of the disease, tracking progression, and monitoring treatment response. The aim of this review article is to analyze various OCT based imaging biomarkers and their potential to be considered as surrogate endpoints for diabetic retinopathy, age related macular degeneration, retinitis pigmentosa and vitreomacular interface disorder. These OCT based surrogate markers have been classified as retinal structural alterations (macular central subfield thickness and cube average thickness); retinal ultrastructural alterations (disruption of external limiting membrane and ellipsoid zone, thinning of retinal nerve fiber layer and ganglion cell layer); intraretinal microangiopathic changes; choroidal surrogate endpoints; and vitreoretinal interface endpoints.

Conclusion: OCT technology is changing very quickly and throughout this review there are some of the multiple possibilities that OCT based imaging biomarkers will be more useful in the near future for diagnosis, prognosticating disease progression and as endpoint in clinical trials.
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http://dx.doi.org/10.1186/s40942-016-0054-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220620PMC
January 2017

Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy.

Mol Vis 2016 2;22:1352-1360. Epub 2016 Dec 2.

CSIR - Indian Institute of Toxicology and Research, Lucknow, India.

Purpose: To study the correlation between serum levels of vitamin B, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT).

Methods: In a tertiary care center-based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40-65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables.

Results: Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001).

Conclusions: This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135738PMC
January 2018

IMPACT OF VITREORETINAL INTERFACE ARCHITECTURE ON SUCCESSFUL VITREOMACULAR TRACTION RESOLUTION IN EYES SCHEDULED FOR INTRAVITREAL OCRIPLASMIN THERAPY.

Retina 2017 Jul;37(7):1252-1260

*Department of Ophthalmology, Philipps-University Marburg, Germany; †Institute of Medical Biometry and Epidemiology, Philipps-University Marburg, Marburg, Germany; ‡Department of Ophthalmology, University of Cologne, Cologne, Germany; §Internationale Innovative Ophthalmochirurgie (IIO), Düsseldorf, Germany; ¶Department of Ophthalmology, Knappschaftskrankenhaus Sulzbach, Sulzbach, Germany; **Department of Ophthalmology, Feldkirch State Hospital, Feldkirch, Austria; ††Department of Ophthalmology, Pallas Clinic, Aarau, Switzerland; ‡‡Department of Ophthalmology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany; §§Department of Ophthalmology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany; and ¶¶Department of Ophthalmology, University Medical Center Goettingen, Goettingen, Germany.

Purpose: To evaluate the impact of the vitreoretinal interface architecture, in specific the angle between the posterior vitreous cortex and the internal limiting membrane, on vitreomacular traction (VMT) resolution in eyes treated with intravitreally injected ocriplasmin (Jetrea).

Methods: Retrospective, multicenter cohort study and exploratory data analysis. Spectral domain optical coherence tomography assessments were performed before scheduled ocriplasmin injections. General (age and sex) as well as ocular variables (lens status, presence of epiretinal membrane formations, horizontal diameter of VMT, central retinal thickness, and in particular various prespecified angles between the posterior vitreous cortex and internal limiting membrane) were analyzed to evaluate their impact on successful VMT resolution.

Results: Fifty-nine eyes of 59 patients were included. Univariate analysis of age (odds ratio [OR]: 0.881; 95% CI: [0.812-0.955]; P = 0.0022) and lens status (OR: 11.03; 95% CI: [2.23-54.57]; P = 0.0033) had a significant impact on successful VMT resolution, whereas sex (OR: 0.668; 95% CI: [0.126-2.065]; P = 0.4906), epiretinal membrane formation (OR: 0.581; 95% CI: [0.168-2.006]; P = 0.3903), horizontal diameter of VMT (OR: 0.99930; 95% CI: [0.99825-1.00035]; P = 0.1886), and central retinal thickness (OR: 0.9985; 95% CI: [0.9934-1.00436]; P = 0.56) failed. The angle at 500 μm apart from the fovea centralis, irrespective if measured nasally (OR: 1.135; 95% CI: [1.013-1.272]; P = 0.0289) or temporally (OR: 1.099; 95% CI: [1.001-1.208]; P = 0.0485), showed a significant correlation with VMT resolution.

Conclusion: The angle between the posterior vitreous cortex and the internal limiting membrane 500 μm apart from the fovea centralis correlates with VMT resolution and may be a clinically useful marker for selection of patients to be treated with ocriplasmin. This observation needs to be proven in a prospective confirmatory investigation.
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http://dx.doi.org/10.1097/IAE.0000000000001371DOI Listing
July 2017

Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion.

Graefes Arch Clin Exp Ophthalmol 2017 Mar 8;255(3):457-462. Epub 2016 Sep 8.

Eye Clinic Sulzbach, Knappschaftsklinikum Sulzbach Saar, An der Klinik 10, 66111, Sulzbach/Saar, Germany.

Purpose: Vision loss in central retinal vein occlusion (CRVO) is mostly caused by macular edema (ME) and can be treated with intravitreal bevacizumab injections. The goal of this study was to identify predictive factors for improvement in visual acuity.

Methods: Three hundred and sixteen eyes of six centres having received intravitreal bevacizumab for ME due to CRVO were enrolled in this multicentre, retrospective, interventional case series. The follow-up time was 24 to 48 weeks. Investigated patient characteristics were pretreatment, duration of CRVO prior to the first injection, initial best-corrected visual acuity (BCVA), baseline central retinal thickness as measured by optical coherence tomography, gender, eye, age, comorbidity with glaucoma, systemic hypertension, or diabetes mellitus.

Results: Multiple regression analysis confirmed the following baseline predictive factors for an increase in visual acuity: low BCVA (p < 0.001), high CRT (p < 0.02), and treatment naïve patients (p = 0.03). None of the other investigated patient characteristics could be identified as prognostic factors for increase in visual acuity (p > 0.1).

Conclusions: Intravitreal injections of bevacizumab in a routine clinical setting effectively improved and stabilized BCVA in CRVO. Our large multicenter study identified initial BCVA, baseline CRT, and pre-treatment as prognostic factors for visual improvement.
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http://dx.doi.org/10.1007/s00417-016-3471-2DOI Listing
March 2017

Biocompatibility of the vital dye Acid Violet-17 on retinal pigment epithelial cells.

Clin Ophthalmol 2016 29;10:1435-45. Epub 2016 Jul 29.

Department of Ophthalmology, University of Schleswig-Holstein, Lübeck, Germany.

Purpose: To examine the viability and differentiation of retinal pigment epithelial (RPE) cells after exposure to the vital dye Acid Violet-17 (AV-17).

Methods: Bovine RPE cells were incubated with AV-17 (0.0625-0.5 mg/mL) for 30 seconds or 5 minutes. Viability was determined by live/dead staining, cleaved CASP3 immunostainings, and MTT test. Actin cytoskeleton was visualized by Alexa 488-phalloidin. Immunocytochemistry was performed to determine the levels of ZO-1, CTNNB1, and KRT19.

Results: Exposure to AV-17 at the concentrations of 0.25-0.5 mg/mL resulted in a dose-dependent decrease in viability, the loss of ZO-1 from tight junctions, translocation of CTNNB1 into the cytoplasm and nucleus, disarrangement of the actin cytoskeleton, and a slight increase in KRT19.

Conclusion: AV-17 at a concentration <0.125 mg/mL is likely to be well tolerated by the RPE cells, whereas the concentrations from 0.25 mg/mL onward can reduce viability and induce dedifferentiation particularly after long-term exposure.
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http://dx.doi.org/10.2147/OPTH.S105695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975140PMC
August 2016

Superior Rim Stability of the Lens Capsule Following Manual Over Femtosecond Laser Capsulotomy.

Invest Ophthalmol Vis Sci 2016 05;57(6):2839-49

Department of Ophthalmology, University of Basel, Basel, Switzerland 6Winterthur Cantonal Hospital, Winterthur, Switzerland 7Centro Ticinese di Chirurgia Ambulatoriale Avanti, Lugano, Switzerland.

Purpose: Cataract surgery requires the removal of a circular segment of the anterior lens capsule (LC) by manual or femtosecond laser (FL) capsulotomy. Tears in the remaining anterior LC may compromise surgical outcome. We investigated whether biophysical differences in the rim properties of the LC remaining in the patient after manual or FL capsulotomy (FLC) lead to different risks with regard to anterior tear formation.

Methods: Lens capsule samples obtained by either continuous curvilinear capsulorhexis (CCC) or FLC were investigated by light microscopy, laser scanning confocal microscopy, and scanning electron microscopy; atomic force microscopy (AFM) was used to test the biomechanical properties of the LC. The mechanical stability of the LC following either of the two capsulotomy techniques was simulated by using finite-element modeling.

Results: Continuous curvilinear capsulorhexis produced wedge-shaped, uniform rims, while FLC resulted in nearly perpendicular, frayed rims with numerous notches. The LC is composed of two sublayers: a stiff epithelial layer that is abundant with laminin and a softer anterior chamber layer that is predominantly made from collagen IV. Computer models show that stress is uniformly distributed over the entire rim after CCC, while focal high stress concentrations are observed in the frayed profiles of LC after FLC, making the latter procedure more prone to anterior tear formation.

Conclusions: Finite-element modeling based on three-dimensional AFM maps indicated that CCC leads to a capsulotomy rim with higher stress resistance, leading to a lower propensity for anterior radial tears than FLC.
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http://dx.doi.org/10.1167/iovs.15-18355DOI Listing
May 2016

INTRAVITREAL INJECTIONS OF ZIV-AFLIBERCEPT FOR DIABETIC MACULAR EDEMA: A Pilot Study.

Retina 2016 Sep;36(9):1640-5

Department of Ophthalmology, Federal University of São Paulo-Paulista Medical School, São Paulo, Brazil.

Purpose: Diabetic macular edema is the leading cause of blindness in young adults in developed countries. Beyond metabolic control, several therapies have been studied such as laser treatment and intravitreal injections of corticosteroids or anti-vascular endothelial growth factor drugs. In terms of public health the long-term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study sought to evaluate the efficacy and safety of intravitreal injections of ziv-aflibercept for the treatment of diabetic macular edema.

Methods: Seven consecutive patients with diabetic macular edema were enrolled. A complete examination, including full-field electroretinography, visual acuity, central retinal thickness, and evaluation of systemic and ocular complications, was performed before and at 24 weeks after intravitreal injections of ziv-aflibercept. The seven patients were submitted to six consecutive intravitreal injections of ziv-aflibercept with a 4-week interval.

Results: No significant differences were found in the amplitude or implicit time of any electroretinography component after intravitreal injections of ziv-aflibercept, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at 24 weeks (P < 0.05). The central retinal thickness significantly decreased during the course of 24 weeks.

Conclusion: Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.
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http://dx.doi.org/10.1097/IAE.0000000000001000DOI Listing
September 2016

Association of serum N(ε)-Carboxy methyl lysine with severity of diabetic retinopathy.

J Diabetes Complications 2016 Apr 11;30(3):511-7. Epub 2015 Dec 11.

Developmental Toxicology Division, CSIR- Indian Institute of Toxicology Research, Lucknow, India.

Purpose: To correlate serum levels of N-epsilon-carboxy methyl lysine (N(ε)-CML) with severity of retinopathy, in vivo macular edema and disruption of external limiting membrane (ELM) and photoreceptor ellipsoid zone in type 2 diabetes mellitus (DM).

Methods: Consecutive cases of type 2 DM [diabetes mellitus with no retinopathy (No DR) (n=20); non- proliferative diabetic retinopathy (NPDR) with diabetic macular edema (n=20); proliferative diabetic retinopathy with diabetic macular edema (PDR) (n=20)] and healthy controls (n=20) between the ages of 40 and 65 years were included (power of study=93.8%). In vivo histology of retinal layers was assessed using spectral domain optical coherence tomography. Every study subject underwent macular thickness analysis using the macular cube 512×128 feature. Disruption of ELM and photoreceptor ellipsoid zone was graded: grade 0, no disruption of ELM and ellipsoid zone; grade 1, ELM disrupted and ellipsoid zone intact; grade 2, both ELM and ellipsoid zone disrupted. Data were statistically analyzed.

Results: The mean levels of N(ε)-CML were 31.34±21.23 ng/ml, 73.88±35.01 ng/ml, 91.21±66.65 ng/ml, and 132.08±84.07 ng/ml in control, No DR, NPDR and PDR respectively. N(ε)-CML level was significantly different between the study groups (control, No DR, NPDR and PDR) (p<0.001). Mean logMAR visual acuity decreased with increased levels of N(ε)-CML (p<0.001). The association of N(Ɛ)CML with the grades of disruption was found to be statistically significant (F value=18.48, p<0.001). Univariate analysis was done with N(Ɛ)-CML as a dependent variable. The values of N(Ɛ)-CML were normalized (log10) and were subjected to univariate analysis with fasting blood glucose level, glycosylated hemoglobin, central subfield macular thickness and cube average thickness among the diseased groups (NPDR and PDR) that act as confounders. It was found that none of the variables had significant effect on N(Ɛ)-CML (fasting blood glucose p=0.12, HBA1c p=0.65, central subfield macular thickness p=0.13, cube average thickness p=0.19). N(Ɛ)-CML tends to be a significant and important predictor of grade of ELM and ellipsoid zone disruption in diabetic retinopathy.

Conclusions: Increased N(ε)-CML levels are associated with increased severity of diabetic retinopathy, macular edema and structural changes in macula that is ELM and ellipsoid zone disruption, which serves as a prognosticator of visual outcome.
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http://dx.doi.org/10.1016/j.jdiacomp.2015.12.009DOI Listing
April 2016

Routes for Drug Delivery to the Eye and Retina: Intravitreal Injections.

Dev Ophthalmol 2016 26;55:63-70. Epub 2015 Oct 26.

The advantage of intravitreal injections is an immediate and increased therapeutic effect in the intended retinal tissue. The accuracy, precision and reproducibility of the delivered volume depend on the size of the syringe and the physician's manual experience. The eyelids and eyelashes are usually disinfected using a povidone-iodine solution (10%); a sterile speculum is placed and drops of povidone-iodine (5%) are applied. The use of adequate anesthetic topical lidocaine 2% is required. The injection site should be located 3.5-4 mm posterior to the limbus. The angle of the incision through the sclera may be directed in an oblique fashion of 30°. The diameter of the needle should be smaller than 25 G, and the injected volume should be limited to 0.15 ml without a routine paracentesis. The incidence of lens injury is 0.006% (2/32,318) and 0.013% (5/35,942) for rhegmatogenous retinal detachments. The rate of suspected endophthalmitis is 0.018% after bevacizumab and 0.027% after ranibizumab injections. Sterile inflammations have been observed after Avastin injections. The concentrations of vascular endothelial growth factor inhibitors decline in a monoexponential fashion. The half-life of unbound bevacizumab is 9.82 days and that of ranibizumab 7.19 days.
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http://dx.doi.org/10.1159/000431143DOI Listing
June 2016