[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.

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.

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.

[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.

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.

Intravitreal functional plasminogen in eyes with branch retinal vein occlusion.

PURPOSE: To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown. METHODS: Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown. RESULTS: Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03-3.9%N). Patients suffering from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003). CONCLUSIONS: Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations.

Intravitreal vascular endothelial growth factor.

PURPOSE: To evaluate whether a specific pre-analytical stabilization regimen is needed for naïve vitreous taps to detect true values of intrinsic VEGF levels. METHODS: Fourteen consecutive patients with different vitreomacular pathologies without blood-retina-barrier breakdown were scheduled for standard 23-gauge three-port pars plana vitrectomy, and naïve vitreous taps were sampled at the beginning of each procedure. The extracted vitreous specimen was split; one half was immediately stored in a -20 °C freezer (unstabilized samples) and the other half was instantly stabilized with albumin (2.5 % final conc.), followed by arginine stabilization (1.25 M final conc.) and consecutively stored in a -20 °C freezer (stabilized samples). RESULTS: Intravitreal VEGF was detected in all 14 analyzed samples (100 %). VEGF levels were shown to be 46.5 pg/ml ± 62.3 pg/ml (MV ± SD; range: 5.99-232.3 pg/ml) in unstabilized, and 120.4 pg/ml ± 94.4 pg/ml (range: 42.9 pg/ml-289.6 pg/ml) in stabilized vitreous samples. Intravitreal VEGF levels in stabilized vitreous samples were on average 2.6-fold, and thus significantly higher than in unstabilized taps of same eyes (p = 0.001, Wilcoxon test). VEGF levels in stabilized vitreous samples can be up to 8.5 times higher than in corresponding unstabilized vitreous taps of same eyes (bootstrap analysis). Intravitreal VEGF levels in unstabilized samples correlate with those in stabilized vitreous taps (r = 0.594; p = 0.025; Pearson). CONCLUSIONS: An adequate pre-analytic stabilization regimen is needed to evaluate the most accurate intravitreal VEGF levels. This in turn will result in a better understanding of the physiological as well as pathological role of VEGF within the eye. Furthermore, knowing the true value of intravitreal VEGF levels will help to calculate the dosage of intravitrealy applied anti-VEGF drugs.

Intravitreal functional plasminogen is elevated in central retinal vein occlusion.

PURPOSE: To detect intravitreal functional plasminogen in vitreous samples of patients with recent onset of central retinal vein occlusion (CRVO) and to demonstrate significantly higher intravitreal plasminogen in CRVO patients in comparison to controls. METHODS: Prospective clinical case series of 13 consecutive patients with recent onset of CRVO scheduled for core pars plana vitrectomy and 10 consecutive patients undergoing standard pars plana vitrectomy for routine macular surgery or vitreal floater removal. In all 23 cases, vitreous taps were extracted from the central vitreous body, and plasminogen was functionally determined in a new ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). RESULTS: Plasminogen was detected in all analyzed samples (n = 23), and mean plasminogen was revealed to be 1.33 ± 1.73% (mean ± SD), with a range of 0.03-7.8%N. Patients with recent onset of CRVO exhibited significantly higher intravitreal plasminogen (2.19 ± 1.89%N) in comparison to controls (0.20 ± 0.21%N; p < 0.001, Mann-Whitney U test). CONCLUSION: Due to significantly increased intravitreal plasminogen in patients with recent onset of CRVO, intravitreally administered tissue plasminogen activator might be an option to induce posterior vitreous detachment (enzymatic vitreolysis) in CRVO patients.

Intracameral concentrations of the fibrinolytic system components in patients with age-related macular degeneration.

PURPOSE: To detect the intracameral concentrations and activities of plasminogen and other components of the fibrinolytic system, and to investigate whether those concentrations and activities are higher in patients with age-related macular degeneration (AMD) in comparison to healthy controls. METHODS: Prospective case series of 93 patients scheduled for standard phacoemulsification. RESULTS: Mean plasminogen activity in patients with non-exsudative AMD (n = 24) revealed to be 0.06%N, in patients with exudative AMD (n = 7) 0.03%N and in healthy controls (n = 43) 0.02%N (p = 0.38, ANOVA). Plasminogen activator inhibitor I (PAI-1) was detected in neither group. Alpha2-antiplasmin activity was 1.61 U/ml in the non-exudative AMD group (n = 27), 0 U/ml in the exudative AMD group (n = 7) and 0.54 U/ml in the control group (n = 48) (p = 0.1, ANOVA). Concentrations of plasmin-a2-antiplasmin complex (PAP) were detected at levels of 17.91 ng/ml in the non-exudative AMD group (n = 11), of 16.6 ng/ml in the exudative AMD group (n = 5), and of 17.43 ng/ml in the control group (n = 14) (p = 0.92, ANOVA). CONCLUSIONS: Plasminogen is present with a very low activity in aqueous humor. There are no significant differences in aqueous humor concentrations or activities of plasminogen and other components of the fibrinolytic system between patients with non-exudative AMD, exudative AMD, and healthy controls. Further studies should investigate vitreous samples instead of aqueous humor samples. A careful and accurate workup of obtained intraocular fluids is needed to detect the low concentrations and activities of the parameters analyzed.

The vitreomacular interface in retinal vein occlusion.

PURPOSE: To evaluate the posterior vitreous adhesion status in patients with a history of central or branch retinal vein occlusion and to compare the results with the natural time-course of posterior vitreous detachment in healthy age-related controls. METHODS: A retrospective chart review in terms of the posterior vitreous adhesion status was performed in 132 patients (133 eyes) with a history of a central (CRVO) or branch (BRVO) retinal vein occlusion. All patients underwent vitrectomy. Based on the operation reports, the vitreous adhesion status was classified as attached, partially detached or completely detached. The results were compared to the natural time-course of posterior vitreous detachment development in healthy age-related controls. RESULTS: Eighty-one eyes met the inclusion and exclusion criteria. Fifty-two eyes (64%) had a history of CRVO and 29 eyes (36%) a history of BRVO, respectively. In the CRVO group, the posterior vitreous was attached in 47 eyes (90%) and completely detached in five eyes (10%). In the BRVO group, the posterior vitreous was attached in 27 eyes (93%), partially detached in 1 eye (3%) and completely detached in another eye (3%). A subdivision into age classes and a comparison with healthy age-related controls [data by Weber-Krause & Eckardt (1997) Ophthalmologe, 94, 619-623] showed in patients between 65 and 69 years of age an attached posterior vitreous cortex in 72% in healthy eyes, in 100% in CRVO (p = 0.109) and in 89% in BRVO (p = 0.440), in patients between 70 and 79 years of age an attached posterior vitreous cortex in 56% in healthy eyes, in 86% in CRVO (p = 0.010) and in 100% in BRVO (p = 0.038) and in patients between 80 and 89 years of age an attached posterior vitreous cortex in 43% in healthy eyes, in 100% in CRVO (p = 0.191) and in 67% in BRVO (p = 0.582) (Fisher's exact t-test). CONCLUSION: In patients with a history of CRVO or BRVO, the posterior vitreous cortex stays attached more frequently in all age groups in comparison with the healthy age-related controls.

Incidence of rhegmatogenous retinal detachments after intravitreal antivascular endothelial factor injections.

PURPOSE: To determine the incidence of rhegmatogenous retinal detachments (RD) after intravitreal injection in six high-volume centres. METHODS: A consecutive, interventional, multicenter case series measured the incidence of RD in patients receiving intravitreal anti-VEGF. A total of 35 942 intravitreal anti-VEGF injections (the number of the injections determined by review of injection log books over a 3 year period) were performed under sterile conditions with the patient in a supine position. Injections were given 3.5-4.0 mm behind the limbus in a tunnelled fashion. RESULTS: During 36 consecutive months, five RD were reported, between 2 and 6 days after the injection. Of the affected eyes, four were myopic -1.75 to -5.5 dpt. The incidence rate of rhegmatogenous RD was 0.013% (5/35 942) per injection. CONCLUSIONS: The incidence of RD in our community setting was very low (1 per 7188 injections). All RD occurred during the early postoperative period. The risks of RD can be minimized by a careful injection technique.

Combined intravitreal anti-vascular endothelial growth factor (Avastin) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma.

OBJECTIVE: Retinal capillary haemangioma complications are characterized by progressive exudation with consecutive intraretinal and subretinal leakage. A successful therapy without side-effects has not been found. We report a case of retinal juxtapapillary capillary haemangioma causing consecutive leakage with macular involvement. The tumour was treated with a combination of anti-vascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) and was followed for 1 year. METHODS: A 44-year-old woman with retinal juxtapapillary capillary haemangioma in the right eye experienced a decrease of visual acuity from 20/20 to 20/60 because of a severe leakage from the tumour involving the macula with lipid depositions. Two sessions of PDT (sparing the part of the haemangioma located within the optic disc) and five injections of bevacizumab were applied in a period of 5 months. Visual acuity, visual field testing, retinal thickness measurements, fundus photography and fluorescein angiography were performed to evaluate the treatment effect. RESULTS: One year after the last injection, visual acuity increased to 20/40. All lipid exudates at the posterior pole resolved. Retinal thickness decreased from 490 to 150 microm with the restoration of normal central macular architecture. Leakage in fluorescence angiography reduced significantly, but hyperfluorescence of the tumour was still evident. Visual field testing and angiography did not show any treatment-related vaso-occlusive side-effects. CONCLUSION: In this single case, the combination of anti-VEGF and PDT appeared to be an effective strategy for the treatment of retinal juxtapapillary capillary haemangioma without side-effects. Further studies with a greater number of eyes and adequate follow-up are necessary to support these first clinical results.