[Diagnosis, treatment and monitoring of diabetic eye disease (Update 2023)]. / Diagnostik, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung (Update 2023).

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these disorders correlates with disease duration and quality of metabolic control. Regular ophthalmological examinations are needed to prevent sight-threatening advanced stages of diabetic eye diseases.

Cytosolic glutaredoxin 1 is upregulated in AMD and controls retinal pigment epithelial cells proliferation via ß-catenin.

Thioredoxin (Trx) family proteins are key players in redox signaling. Here, we have analyzed glutaredoxin (Grx) 1 and Grx2 in age-related macular degeneration (AMD) and in retinal pigment epithelial (ARPE-19) cells. We hypothesized that these redoxins regulate cellular functions and signaling circuits such as cell proliferation, Wnt signaling and VEGF release that have been correlated to the pathophysiology of AMD. ARPE-19 cells were transfected with specific siRNAs to silence the expression of Grx1 and Grx2 and were analyzed for proliferation/viability, migration capacity, ß-catenin activation, and VEGF release. An active site-mutated C-X-X-S Grx1 was utilized to trap interacting proteins present in ARPE-19 cell extracts. In both, AMD retinas and in ARPE-19 cells incubated under hypoxia/reoxygenation conditions, Grx1 showed an increased nuclear localization. Grx1-silenced ARPE-19 cells showed a significantly reduced proliferation and migration rate. Our trapping approach showed that Grx1 interacts with ß-catenin in a dithiol-disulfide exchange reaction. Knock-down of Grx1 led to a reduction in both total and active ß-catenin levels. These findings add redox control to the regulatory mechanisms of ß-catenin signaling in the retinal pigment epithelium and open the door to novel therapeutic approaches in AMD that is currently treated with VEGF-inhibitors.

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.

[Diagnosis, treatment and monitoring of diabetic eye disease (Update 2019)]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung (Update 2019).

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow-up depending on stage of diabetic eye disease are summarized.

Calculating the individual probability of successful ocriplasmin treatment in eyes with VMT syndrome: a multivariable prediction model from the EXPORT study.

BACKGROUND/AIMS: To evaluate predictive factors for the treatment success of ocriplasmin and to use these factors to generate a multivariate model to calculate the individual probability of successful treatment. METHODS: Data were collected in a retrospective, multicentre cohort study. Patients with vitreomacular traction (VMT) syndrome without a full-thickness macular hole were included if they received an intravitreal injection (IVI) of ocriplasmin. Five factors (age, gender, lens status, presence of epiretinal membrane (ERM) formation and horizontal diameter of VMT) were assessed on their association with VMT resolution. A multivariable logistic regression model was employed to further analyse these factors and calculate the individual probability of successful treatment. RESULTS: 167 eyes of 167 patients were included. Univariate analysis revealed a significant correlation to VMT resolution for all analysed factors: age (years) (OR 0.9208; 95% CI 0.8845 to 0.9586; p<0.0001), gender (male) (OR 0.480; 95% CI 0.241 to 0.957; p=0.0371), lens status (phakic) (OR 2.042; 95% CI 1.054 to 3.958; p=0.0344), ERM formation (present) (OR 0.384; 95% CI 0.179 to 0.821; p=0.0136) and horizontal VMT diameter (µm) (OR 0.99812; 95% CI 0.99684 to 0.99941, p=0.0042). A significant multivariable logistic regression model was established with age and VMT diameter. CONCLUSION: Known predictive factors for VMT resolution after ocriplasmin IVI were confirmed in our study. We were able to combine them into a formula, ultimately allowing the calculation of an individual probability of treatment success with ocriplasmin in patients with VMT syndrome without FTHM.

Ocriplasmin treatment for vitreomacular traction in real life: can the indication spectrum be expanded?

PURPOSE: To evaluate the efficacy of intravitreal ocriplasmin for the resolution of vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) in the clinical setting and to assess whether the indication spectrum of this treatment modality can be expanded beyond that of the MIVI-TRUST trials. METHODS: The records of patients with VMT with or without FTMH, who were treated with intravitreal ocriplasmin were reviewed. Patients were divided in two groups. In the first group, VMT with or without FTMH was present without any other macular pathology. In the second group, VMT with or without FTMH occurred alongside of other macular disease including age-related macular degeneration, diabetic maculopathy and post-operative pseudophakic cystoid macular edema. RESULTS: Release of the VMT was achieved in 12/20 patients (12/20 eyes) of the first group. 16 eyes in this group met 3 or more criteria known to be associated with favorable prognosis after intravitreal ocriplasmin treatment. No cases of release of the VMT were observed in the second group, which included 15 patients (15 eyes). Significant improvement of visual acuity and reduction of the central macular thickness was observed only in the subgroup of eyes which responded to treatment. CONCLUSIONS: Concomitant macular pathology was a significant factor for treatment failure and we suggest that ocriplasmin should be regarded with caution in these cases. Careful patient selection for treatment with ocriplasmin using specific criteria in the clinical setting can provide superior results to those reported in the MIVI-TRUST trials.

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.

Outcome of intravitreal dexamethasone implant for the treatment of ranibizumab-resistant macular edema secondary to retinal vein occlusion.

To assess the effect of intravitreal dexamethasone implant (Ozurdex) for the treatment of macular edema secondary to retinal vein occlusion (RVO) resistant to repeated intravitreal ranibizumab injection. Retrospective review of 11 patients (11 eyes) with ranibizumab-resistant macular edema secondary to RVO. Macular edema was considered refractory to ranibizumab if no change of the pattern of macular fluid on optical coherence tomography and no change of best-corrected visual acuity (BCVA) was observed after at least three consecutive monthly injections, excluding the loading dose. A single Ozurdex injection was performed and BCVA and central foveal thickness (CFT) were reviewed 2, 3, and 6 months after treatment. Mean BCVA improved significantly from 0.51 logarithm of the minimal angle of resolution (log MAR) at baseline to 0.3 log MAR (p = 0.03) at 2 months and 0.29 log MAR (p = 0.003) at 3 months. There was no significant difference in the BCVA between baseline at 6 months (p = 0.62). Mean CFT reduced significantly from 538 µm at baseline to 281 µm at 2 months (p = 0.00003), 281 µm at 3 months (p = 0.00003), and 445 µm at 6 months (p = 0.03). Treatment with Ozurdex results in improvement of BCVA and reduction of CFT in patients with ranibizumab refractory macular edema due to RVO at 3 months. However, it seems that the visual acuity gain may not last up to 6 months, so that a re-injection before this time point could be considered.

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

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.

[Diagnosis, treatment and monitoring of diabetic eye control]. / Diagnose, Therapie und Verlaufskontrolle der diabetischen Augenerkrankung.

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these defects correlates with disease duration and quality of metabolic control. Recommendations of the Austrian Diabetes Association for diagnosis, therapeutic procedures and requirements for adequate follow up depending on stage of diabetic eye disease are summarized.

Is Optical Coherence Tomography a Useful Tool to Objectively Detect Actual Posterior Vitreous Adhesion Status?

Purpose. To objectively detect true posterior vitreous cortex (PVC) adhesion status using a commercially available swept-source OCT device (DRI OCT-1, Atlantis(©)). Material and Methods. Case report, review of the literature, and methodical discussion of concepts to improve OCT-guided PVC imaging. Results. Standard OCT imaging misdiagnosed PVC adhesion status as totally detached in this case report when using a horizontal 6 mm scan only. Contrariwise imaging the same eye with a 12 mm horizontal scan, partial posterior vitreous detachment (PVD) and the presence of a bursa premacularis were clearly discernible. Besides a broader scan, specific scan patterns, highest resolution, and contrast sensitivity, an anterior-to-posterior adjusted scan through the entire vitreous as well as the detection of characteristic undulating aftermovements might enhance the capability of OCT imaging to detect true PVC adhesion status. Conclusions. Further developments are needed to address these issues and to establish OCT recordings as the standard and objective method of choice in PVC adhesion status imaging.

The impact of posterior vitreous adhesion on ischaemia in eyes with retinal vein occlusion.

PURPOSE: To evaluate whether posterior vitreous adhesion (PVA) contributes to retinal ischaemia in eyes suffering from central (CRVO) or branch retinal vein occlusion (BRVO). METHODS: Retrospective patient chart analysis of eyes with CRVO/BRVO receiving pars-plana vitrectomy (ppV). Prior to surgery fluorescence angiography was conducted to classify RVO as ischaemic or not. RESULTS: Sixty eyes were included, thereof 36 (60%)/24 (40%) with CRVO/BRVO. In the CRVO group, 17 (47%)/19 (53%) eyes were classified as ischaemic/non-ischaemic. Respective results for BRVO-affected eyes were 16 (67%)/8 (33%). PVA/posterior vitreous detachment (PVD) was found in 33 (92%)/3 (8%) eyes with CRVO and in 23 (96%)/1 (4%) patients suffering from BRVO. Value differences of PVA/PVD between ischaemic- and non-ischaemic-typed RVO failed statistical significance for both, CRVO (p = 0.095) and BRVO (p = 1.0). CONCLUSIONS: Posterior vitreous adhesion had no impact on retinal ischaemia in this investigation. As an attached posterior vitreous cortex acts as a scaffold and thus significantly increases neovascularization (NV) development in ischaemic-typed RVO, a prospective study evaluating the effect of enzymatic vitreolysis is indicated.

20 g PPV with indocyanine green-assisted ILM peeling versus 23 g PPV with brilliant blue G-assisted ILM peeling for epiretinal membrane.

To compare the anatomical and visual outcomes of 20 gauge (g) pars plana vitrectomy (PPV) with indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling and 23 g PPV with brilliant blue G (BBG)-assisted ILM peeling for idiopathic epiretinal membrane (ERM). 38 eyes of 38 patients with idiopathic ERM were included. They were divided in two groups: group 1 (18 eyes) underwent 20 g PPV with ICG-assisted ILM peeling and group 2 (20 eyes) 23 g PPV with BBG-assisted ILM peeling. Postoperative best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared. Average BCVA in group 1 improved significantly from 0.60 logarithm of the minimal angle of resolution (log MAR) at baseline to 0.3 log MAR postoperatively. Average BCVA in group 2 improved significantly from 0.60 log MAR at baseline to 0.3 log MAR postoperatively. Mean CMT reduced significantly from 473 to 375 µm in group 1 and from 486 to 396 µm in group 2. There were no significant differences in the BCVA and CMT between the groups. Both surgical methods appeared to be safe and provided similar anatomical and visual outcomes.