Accelerated corneal cross-linking (18mW/cm2 for 5 min) with HPMC-riboflavin in progressive keratoconus - 5 years follow-up.

PURPOSE: To evaluate long-term results of accelerated corneal cross-linking (ACXL) in patients with progressive keratoconus, seventy-four eyes of 53 patients with progressive keratoconus (documented Kmax progression > 1D/a) who underwent ACXL (18mW/cm2 for 5 min) were included in a retrospective observational clinical study. The investigation focused on tomographic and keratometric parameters, refractive data, and visual outcomes at 5 years follow-ups. METHODS: Corrected distance visual acuity (CDVA), slit lamp, and Pentacam® examinations were conducted, including assessments of thinnest corneal point (TP), minimum radius (Rmin), corneal astigmatism, and maximum anterior keratometry (Kmax). These examinations were performed two weeks before the surgery and, on average, 56 months after the surgery. In a subgroup of 24 eyes, Pentacam® examination data from an intermediate visit at 12 months until the final visit was evaluated to confirm continuous stability. The ACXL protocol included corneal abrasion, hydroxypropylmethylcellulose (HPMC)-riboflavin eye drops administered every 5 min for a total duration of 30 min, and irradiation with 18mW/cm2 for 5 min using riboflavin eye drops applied every minute during the irradiation process. Intraoperatively, minimal corneal pachymetry of > 400 µm was ensured in every patient. RESULTS: After 56 months, all values exhibited statistically significant changes (paired t-test; CDVA p = 0.002; Kmax p < 0.001; Rmin p < 0.001; astigmatism p = 0.03; TP p < 0.001). In the subgroup analysis of 24 eyes, which included tomographical and keratometric parameters, no statistically significant changes were observed during the last 12 months of observation (paired t-test; Kmax p = 0.72; Rmin p = 0.67; astigmatism p = 0.72). Treatment failure was strictly defined as an increase in Kmax (> 1D) during the 5-year follow-up and was observed in only 3 eyes (4%). CONCLUSIONS: ACXL is an effective and safe treatment for patients with progressive keratoconus. Our results demonstrate improvements in functional and tomographical outcomes even after high-energy ACXL (18mW/cm2 for 5 min) over a long-term period of 56 months. Our analysis indicates stable conditions in previously progressive keratoconus, particularly during the final year of the observation period. The treatment failure rate was 4%.

VERTICAL AND HORIZONTAL METAMORPHOPSIA ONE YEAR AFTER SURGERY FOR MACULAR HOLES ≤ 500 µ m WITH AND WITHOUT INVERTED INTERNAL LIMITING MEMBRANE FLAP.

PURPOSE: To investigate the effect of an inverted internal limiting membrane flap (IF) and other factors on metamorphopsia after macular hole surgery. METHODS: Prospective case series of patients undergoing pars plana vitrectomy with gas tamponade, with either conventional internal limiting membrane peeling (CP) or an IF, for primary idiopathic macular holes ≤ 500 µ m. Vertical and horizontal metamorphopsia were measured as M-scores (degrees) using M-charts preoperatively and at 2, 6, and 12 months postoperatively. RESULTS: Fifty-three eyes of 53 patients were included of whom 27 underwent CP and 26 were treated with an IF. After macular hole surgery, all patients were pseudophakic. Vertical and horizontal metamorphopsia improved from 1.08 (±0.51) and 0.98 (±0.70) preoperatively to 0.58 (±0.37) and 0.45 (±0.36) at 2 months ( P < 0.01), with no further significant improvement at 6 months (0.39 [±0.31], P = 0.07 and 0.31 [±0.28], P = 0.18) or at 12 months (0.37 [±0.30], P = 0.72 and 0.28 [±0.28], P = 0.99). There was no significant difference in the mean vertical and horizontal metamorphopsia between patients with CP and with an IF at 2 months ( P = 0.063, P = 0.10), 6 months ( P = 0.25, P = 0.16), or 12 months ( P = 0.62, P = 0.22). Preoperative vertical M-score improved at 12 months after macular hole surgery by 61% and 64% in the CP and IF groups, respectively ( P = 0.84), and the horizontal M-score by 65% and 71%, respectively ( P = 0.98). CONCLUSION: The use of an IF has no evident bearing on the degree of postoperative metamorphopsia 12 months after surgical repair of macular holes ≤ 500 µ m.

LASER FLARE PHOTOMETRY IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: An Evaluation of 2,487 Cases.

PURPOSE: Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD). METHODS: The authors measured laser flare values of all 3,048 prescreened patients excluding those with comorbidities. A mixed regression analysis evaluated the strength of the influencing factors like age, sex, lens status, and presence and extent of RRD on laser flare. RESULTS: Rhegmatogenous retinal detachment was more frequent in men (65.8%) than in women (34.2%, P < 0.001) and in right (52%) than in left eyes (48%, P = 0.045). Phakic RRD affected less quadrants and was less likely to be associated with macula-off status than pseudophakic RRD (48.4% vs. 58.0% macula off, 23% vs. 31% ≥3 quadrants, P < 0.001). Laser flare of affected eyes was significantly higher compared with fellow eyes (12.6 ± 15.2 vs. 8.3 ± 7.4 pc/ms, P < 0.001). The factors age, sex, lens status, presence of RRD, and the number of quadrants affected were independent influencing factors on laser flare. R 2 was 0.145 for phakic and 0.094 for pseudophakic eyes. CONCLUSION: The results indicate that there may be more factors affecting laser flare than previously assumed. This might limit flare as predictive value for PVR and retinal redetachment.

INFLUENCE OF PREOPERATIVE POSTURING ON SUBFOVEAL FLUID HEIGHT IN MACULA-OFF RETINAL DETACHMENTS.

PURPOSE: To evaluate the effect of preoperative posturing on subfoveal fluid height (SFFH) in macula-off retinal detachment. METHODS: A prospective study including patients with macula-off retinal detachment with SFFH measurable on optical coherence tomography (OCT) and duration of loss of central vision (LCV) ≤ 7 days. Linear OCT volume scans were performed at baseline, after 1 minute, 1 hour, 4 hours, and on the next morning. For the first hour, all patients remained in an upright position. Patients were then either instructed to posture until the surgery according to the location of the primary retinal break (posturing group) or were not given any instructions (control group). RESULTS: Twenty-four patients were included in the posturing group and 11 patients in the control group. There was no significant change in SFFH between baseline, 1 minute, 1 hour, and 4 hours. The mean SFFH in the control group increased by 243 µ m from 624 (±268) µ m at baseline to 867 (±303) µ m the next morning ( P < 0.01) but decreased in the posturing group by 150 µ m from 728 (±416) to 578 (±445) µ m ( P = 0.03). There was a significant association of the SFFH the next morning with posturing ( P < 0.01) and SFFH at baseline ( P < 0.01), but not with location of primary break ( P = 0.20). The change in SFFH from baseline to the next morning was significantly associated with posturing and primary break location ( P < 0.01), but not with SFFH at baseline ( P = 0.21). CONCLUSION: Preoperative posturing is an effective measure to prevent progression of macular detachment in macula-off retinal detachment.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Optical coherence tomography angiography indicates subclinical retinal disease in neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are neuroinflammatory diseases of the central nervous system. Patients suffer from recurring relapses and it is unclear whether relapse-independent disease activity occurs and whether this is of clinical relevance. OBJECTIVE: To detect disease-specific alterations of the retinal vasculature that reflect disease activity during NMOSD. METHODS: Cross-sectional analysis of 16 patients with NMOSD, 21 patients with relapsing-remitting multiple sclerosis, and 21 healthy controls using retinal optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), measurement of glial fibrillary acidic protein (GFAP) serum levels, and assessment of visual acuity. RESULTS: Patients with NMOSD but not multiple sclerosis revealed lower foveal thickness (FT) (p = 0.02) measures and an increase of the foveal avascular zone (FAZ) (p = 0.02) compared to healthy controls independent to optic neuritis. Reduced FT (p = 0.01), enlarged FAZ areas (p = 0.0001), and vessel loss of the superficial vascular complex (p = 0.01) were linked to higher serum GFAP levels and superficial vessel loss was associated with worse visual performance in patients with NMOSD irrespective of optic neuritis. CONCLUSION: Subclinical parafoveal retinal vessel loss might occur during NMOSD and might be linked to astrocyte damage and poor visual performance. OCT-A may be a tool to study subclinical disease activity during NMOSD.

Visual improvement and regeneration of retinal layers in eyes with small, medium, and large idiopathic full-thickness macular holes treated with the inverted internal limiting membrane flap technique over a period of 12 months.

PURPOSE: This study aims to compare the improvement of best-corrected visual acuity (BCVA) and the reduction in defect length of external limiting membrane (ELM) and ellipsoid zone (EZ) in small ([Formula: see text] 250 µm), medium ([Formula: see text] 250 µm), and large ([Formula: see text] 400 µm) full-thickness macular holes (FTMH) treated with inverted internal limiting membrane (I-ILM) flap technique over a follow-up period of 12 months. METHODS: Ninety-one eyes of 87 patients were enrolled in this retrospective study. BCVA and spectral-domain optical coherence tomography (SD-OCT) were conducted preoperatively as well as after 1, 3, 6, 9, and 12 months postoperatively. The defect length of the ELM and the EZ was measured using the caliper tool at each follow-up time point. RESULTS: BCVA improved significantly in the group of small, medium, and large FTMH over the time of 12 months, whereby the improvement did not depend on FTMH size over 9 months. Only after 12 months, large FTMH showed significantly higher BCVA improvement compared to small and medium FTMH. The closure rate was 100% (91/91). The defect length of ELM and EZ reduced continuously over the period of 12 months. There was a significant correlation between defect length of ELM and EZ with postoperative BCVA. CONCLUSION: The I-ILM flap technique has very good morphological and functional outcomes in small, medium, and large FTMH over a long-time period, indicating that it can be considered as a treatment option in small and medium FTMH. The defect length of ELM and EZ is directly connected to postoperative BCVA.

Anatomical and functional outcomes of pneumatic vitreolysis for treatment of vitreomacular traction with and without macular holes.

PURPOSE: To evaluate the outcome of pneumatic vitreolysis (PVL) for vitreomacular traction (VMT) with or without full thickness macular hole (MH) < 400 µm. METHODS: Forty-seven eyes of 47 patients were included who had undergone PVL for VMT with or without MH. Main outcome measures were release of VMT, MH closure, best-corrected visual acuity (BCVA) and adverse events. RESULTS: Thirty-three patients had isolated VMT and 14 patients VMT with a MH. Four weeks after PVL, the overall VMT release rate was 35/47 (74.5%): 25/37 (67.6%) in phakic and 10/10 (100%) in pseudophakic eyes (p = 0.03). Four of 14 MH (28.6%) were closed. Twenty-two of 47 (46.8%) eyes required a subsequent PPV: 12/33 (36.4%) in the VMT only group and 10/14 (71.4%) in the VMT with MH group. Mean BCVA improved from 0.48 (± 0.24) to 0.34 (± 0.23) logMAR at 6 months in patients with VMT alone (p < 0.001), and from 0.57 (± 0.27) to 0.41 (± 0.28) logMAR in patients with VMT and MH (p = 0.008). Adverse events included new formation of a large MH in 4/33 (12.1%) eyes, failure of MH closure in 10/14 (71.4%) eyes, progression of mean minimum linear diameter (MLD) MH size from baseline 139 (± 67) to 396 (± 130) µm (p < 0.001) and development of a retinal detachment in 4/47 (8.5%) eyes. CONCLUSION: While PVL leads to a high VMT release rate particularly in pseudophakic eyes, it is associated with a relatively high incidence of MH formation, MH size progression and retinal detachment.

Detection of SARS-CoV-2-RNA in post-mortem samples of human eyes.

PURPOSE: To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. METHODS: In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. RESULTS: SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. CONCLUSION: SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.

A Tool for High-Resolution Volumetric Optical Coherence Tomography by Compounding Radial-and Linear Acquired B-Scans Using Registration.

Optical coherence tomography (OCT) is a medical imaging modality that is commonly used to diagnose retinal diseases. In recent years, linear and radial scanning patterns have been proposed to acquire three-dimensional OCT data. These patterns show differences in A-scan acquisition density across the generated volumes, and thus differ in their suitability for the diagnosis of retinal diseases. While radial OCT volumes exhibit a higher A-scan sampling rate around the scan center, linear scans contain more information in the peripheral scan areas. In this paper, we propose a method to combine a linearly and radially acquired OCT volume to generate a single compound volume, which merges the advantages of both scanning patterns to increase the information that can be gained from the three-dimensional OCT data. We initially generate 3D point clouds of the linearly and radially acquired OCT volumes and use an Iterative Closest Point (ICP) variant to register both volumes. After registration, the compound volume is created by selectively exploiting linear and radial scanning data, depending on the A-scan density of the individual scans. Fusing regions from both volumes with respect to their local A-scan sampling density, we achieve improved overall anatomical OCT information in a high-resolution compound volume. We demonstrate our method on linear and radial OCT volumes for the visualization and analysis of macular holes and the surrounding anatomical structures.

Functional recovery after macula involving retinal detachment and its correlation with preoperative biomarkers in optical coherence tomography.

To introduce an ETDRS grid-based classification for macula involving retinal detachment (MIRD) with or without center (foveal) involvement and to identify biomarkers in preoperative optical coherence tomography (OCT) associated with a favorable postoperative functional outcome in eyes with center involving retinal detachment (CIRD). One hundred and two eyes of 102 consecutive patients (f/m: 35/67) with primary rhegmatogenous retinal detachment, preoperative evidence of MIRD (perifoveal involvement of ≤ 6.0 mm), and successful retinal surgery were included in this retrospective cohort study. Eyes were assigned to 5 grades of MIRD (G1-G5), based on the extent of detachment in the ETDRS grid. Eyes with a detached foveal status (CIRD) were assigned to G4 or G5. In CIRD, the following OCT biomarkers were quantified and correlated with mean BCVA (logMAR) at 3 months postsurgery, using univariate and multivariable regression models: grade of detachment, extent of intraretinal edema, height of foveal detachment, subretinal folds, and epiretinal membrane. Forty-one of 102 eyes (40.2%) presented with an attached foveal status, defined as either outer (G1: 11.8%) or inner (G2: 18.6%) macular involvement or fovea-threatening MIRD (G3: 9.8%). Sixty-one eyes (59.8%) showed CIRD (G4 or G5). Eyes with CIRD had significantly worse postoperative BCVA than eyes without foveal involvement (0.355 logMAR vs. 0.138 logMAR, p<0.001). If CIRD was limited to three outer ETDRS quadrants (G4), mean BCVA was better compared to CIRD involving all four ETDRS quadrants (G5) (0.254 logMAR vs. 0.522 logMAR, p<0.001). Reading ability (BCVA ≤ 0.4 logMAR) was restored in 97.6% of eyes with G1-G3 compared to 86.9% of eyes with G4 (p=0.072) and 52.4% of eyes with G5 (p<0.001). In multivariable regression analysis of eyes with CIRD, a lower grade of detachment (G4 vs. G5: p<0.05) and lower extent of cystoid edema (focal/none vs. wide: p<0.001) were both associated with better postoperative function. The functional outcome after MIRD may be worse in the presence of foveal involvement (CIRD), but a lower grade of detachment and the absence of intraretinal edema can predict a good recovery in spite of CIRD.

Inverted internal limiting membrane flap technique in eyes with large idiopathic full-thickness macular hole: long-term functional and morphological outcomes.

PURPOSE: To investigate morphological and functional outcomes of the inverted internal limiting membrane (I-ILM) flap technique in large (≥ 400 µm) idiopathic full-thickness macular holes (FTMH) over a follow-up period of 12 months. METHODS: In this retrospective study, 55 eyes of 54 consecutive patients were enrolled. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT, Heidelberg, Spectralis) were performed preoperatively as well as 1, 3, 6, 9, and 12 months postoperatively. Special focus was put on the reintegration of outer retinal layers and the different ILM flap appearances. RESULTS: FTMH closure rate was 100% (55/55). BCVA significantly improved over the follow-up period of 12 months from 0.98 ± 0.38 LogMAR preoperatively to 0.42 ± 0.33 LogMAR at 12 months postoperatively (p < 0.001). There was no significant correlation between the three different ILM flap appearances and BCVA. Better preoperative BCVA, complete restoration of the external limiting membrane (ELM), higher macular hole index (MHI), and smaller MH base diameter were associated with higher improvement of BCVA. CONCLUSION: Our study highlights the favorable morphological and functional outcomes of the I-ILM flap technique in the short as well as in the long term. While complete ELM restoration revealed to be an important factor for improvement in BCVA, the different postoperative ILM flap appearances seem not to be related to BCVA.

[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.

Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis.

BACKGROUND: Patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) may show alterations of retinal layer architecture as measured by optical coherence tomography. Little is known about changes in the retinal vascular network during MS. OBJECTIVE: To characterize retinal vessel structures in patients with MS and CIS and to test for associations with MS disease activity. METHOD: In all, 42 patients with MS or CIS and 50 healthy controls underwent retinal optical coherence tomography angiography (OCT-A) with analysis of the superficial and deep vascular plexuses and the choriocapillaries. We tested OCT-A parameters for associations with retinal layer volumes, history of optic neuritis (ON), and the retrospective disease activity. RESULTS: Inner retinal layer volumes correlated positively with the density of both the superficial and deep vascular plexuses. Eyes of MS/CIS patients with a history of ON revealed reduced vessel densities of the superficial and deep vascular plexuses as compared to healthy controls. Higher choriocapillary vessel densities were associated with ongoing inflammatory disease activity during 24 months prior to OCT-A examination in MS and CIS patients. CONCLUSION: Optic neuritis is associated with rarefaction of the superficial and deep retinal vessels. Alterations of the choriocapillaries might be linked to disease activity in MS.

[Retinal Vascular Occlusion: Modern Therapeutic Approaches]. / Retinale Gefäßverschlüsse: Moderne Therapieansätze.

Retinal artery occlusion (RAO) should be evaluated as an emergency and can be seen as an ocular analogue to the cerebral apoplex. Both have the same arteriosclerotic risk factors, which are also responsible for cardiac, circulatory and cerebrovascular diseases. That is why an intensive interdisciplinary clarification is necessary to recognize possible comorbidities in time and, if necessary, to treat them. The current therapeutic possibilities of an acute RAO are very limited in their efficiency regarding visual improvement. Methods for systemic lysis cannot be recommended in routine care because of their significantly increased side-effect profile. However, there is a limited window of time of up to 6 hours after the onset of symptoms in which an intervention appears to be useful at all. On the other hand, the new therapeutic possibilities of retinal vein occlusions (RVO) led to marked visual improvements, especially due to the intravitreal application of anti-VEGF. Safety and efficiency of the individual anti-VEGF drugs are comparable according to clinical trials. Alternatively, the use of intravitreal steroids can be considered, whereby the side-effect profile should be carefully weighed. In the presence of retinal ischaemia, peripheral laser coagulation can have a stabilizing effect on visual acuity and prevents neovascularization. It is postulated that the combination of anti-VEGF and laser therapy might have a symbiotic effect.

[Intraoperative Optical Coherence Tomography in Vitreoretinal Surgery: Clinical Experiences and Future Developments]. / Die intraoperative optische Kohärenztomografie in der Netzhaut-Glaskörper-Chirurgie. Aktuelle Erfahrungen und Ausblick auf künftige Entwicklungsschritte.

PURPOSE: High resolution optical coherence tomography (OCT) enables better visualization of ophthalmic microstructures than conventional imaging. When using an ophthalmic microscope, integrated optical coherence tomography (iOCT) high resolution real time visualization is possible. METHODS: We report on the first 110 patients operated on using a microscope integrated OCT (iOCT) during surgical procedures for the treatment of various posterior segment pathologies. RESULTS: Microstructural changes that appeared during surgery were depicted precisely by iOCT, and the morphology visualized before and after each surgical step was used to help deciding how to adapt the surgical flow. The iOCT data and real-time imaging of retinal anatomy gives the surgeon the possibility of deploying patient- and operation-specific interventional procedures. DISCUSSION: To date, iOCT is only available in standing microscopes with no measurement or tracking features. Moreover, metal instruments currently obscure the scanned images. In the future, non-metal, transparent instruments (OCT-friendly surgical tools), tracking features, an autofocus and higher resolution could enable full and immediate intraoperative SD-OCT diagnostics in real time.

The predictability of ocriplasmin treatment effects: is there consensus among retinal experts? Results from the EXPORT study.

PURPOSE: To evaluate the agreement and predictability of ocriplasmin treatment effects among retinal experts (raters) by assessment of retinal imaging data of eyes treated for vitreomacular traction in nine different centers in Germany and Austria. METHODS: Retrospective cohort study. Combined confocal near-infrared scanning laser ophthalmoscopy and spectral-domain optical coherence tomography images (Spectralis® device, Heidelberg Engineering GmbH, Germany) from 136 eyes of 135 subjects were reviewed by 14 raters using an internet-based grading database and a standardized questionnaire. In addition to the images taken within 2 days prior to treatment, age, gender, and lens status were disclosed to the raters. Treatment success was defined as a complete cleavage of the posterior vitreous cortex at day 28±5. Main outcome was the agreement and predictability among raters for assessment of treatment success. RESULTS: Raters generally accepted starting ocriplasmin treatment (chance for treatment success ≥ 1%) in 22.4 to 69.1% (median 53.2%) of eyes (moderate intra- and interrater agreements with kappa-values of 0.6 and 0.48). The likelihood for a high potential treatment success (equal or higher than 25%) was judged by the raters in 43.4% to 86.0% (median 62.6%) of eyes (moderate intra- and fair interrater agreements with kappa-values of 0.56 and 0.22). Allocating eyes for high potential treatment success overall increased the odds by 3.07, with odds ratios of single raters up to 4.06 to 6.16. CONCLUSIONS: These results underscore the importance of training health care providers in the evaluation of retinal imaging data and also to define characteristic morphological features better in the presence of vitreoretinal interface diseases. The better results of single raters in the predictability of treatment success by the allocation of eyes in the high-potential group indicates the high relevance of the meticulous analysis of retinal images.

VITRECTOMY FOR PERSISTENT MACULAR HOLES FOLLOWING OCRIPLASMIN INJECTION: A Comparative Multicenter Study.

PURPOSE: To determine functional and anatomical outcomes of pars plana vitrectomy for persistent full-thickness macular hole (MH) after intravitreal injection of ocriplasmin. METHODS: This is a multicenter retrospective interventional study of 37 eyes of 37 patients who underwent pars plana vitrectomy with internal limiting membrane peeling for persistent MH after ocriplasmin treatment between December 2013 and December 2015 and comparison with 35 eyes of 35 patients who were offered ocriplasmin injection but underwent pars plana vitrectomy alone without pharmacologic vitreolysis before surgery. In addition, 24 matched pairs (MH diameter at baseline ±5 µm) were analyzed. Clinical data such as visual acuity, intraoperative characteristics, and spectral domain optical coherence tomography images were reviewed. Main outcome measures were visual acuity and MH closure rate. RESULTS: After a mean follow-up period of 9 months, postoperative mean visual acuity showed no significant differences between ocriplasmin-treated eyes (logarithm of minimum angle of resolution 0.37 ± 0.26, Snellen 20/47) and eyes without ocriplasmin treatment (logarithm of minimum angle of resolution 0.39 ± 0.25; Snellen 20/49) (P > 0.9). After ocriplasmin injection, mean MH diameter enlarged from 217 ± 102 µm to 384 ± 239 µm (P < 0.001). Matched-pair analysis revealed no difference in gain of visual acuity between the first visit and the last follow-up (P = 0.29). Macular hole closure was observed in similar proportion in ocriplasmin-treated eyes (97%) and vitrectomy-only eyes (94%) (P > 0.5). CONLCUSION: Eyes with persistent MH after ocriplasmin injection showed significant visual improvement after pars plana vitrectomy. Matched-pair analysis revealed no statistical differences in functional and anatomical postoperative results comparing with eyes of similar MH diameter that proceeded directly to surgery without ocriplasmin pretreatment.