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Purpose: Central serous chorioretinopathy (CSCR) presents itself as a serous detachment of the central neurosensory retina (NR), which may be accompanied by focal detachment of the retinal pigment epithelium (RPE) and changes in the RPE itself. It is often self-limiting; however, if the macular region is affected, visual impairment can be serious. If spontaneous remission does not occur, data on the effectiveness of further treatment options are sparse. We therefore decided to examine the effectiveness of subthreshold laser photocoagulation (ST-LP) on best-corrected visual acuity (BCVA) and subretinal fluid (SRF) resorption. We conducted a retrospective analysis of all patients who underwent ST-LP based on the diagnosis of CSCR in a German university eye hospital from 2009 to 2014., Methods: The diagnosis of CSCR was based on the following criteria: detachment of the NR and possibly the RPE visible on ophthalmoscopy, evidence of SRF on optical coherence tomography (OCT), visualization of one or more source points typical for CSCR in fluorescein angiography, and exclusion of differential diagnoses. The time between the anamnestic onset of symptomatic complaints and ST-LP was determined as well as BCVA and OCT before ST-LP. ST-LP was performed as a subthreshold thermal laser coagulation with a frequency-doubled Nd:YAG continuous-wave laser. Follow-up examinations were scheduled at 4, 8, and 12 weeks after ST-LP., Results: Fifty-four eyes of 49 patients were included in the study. The median age of patients was 47 years. Eighty-nine percent of the included patients were male. Twenty percent of patients had a first manifestation of CSCR, 69% had a recurrence, and 11% had persistent SRF for >6 months. The median visual acuity rose from 0.30 at baseline (BL) to 0.10 at 4 weeks and 0.00 at 8 weeks, before dropping slightly to 0.05 at 12 weeks. Changes of visual acuity in comparison to BL were statistically significant (p < 0.05). The initial median retinal thickness of 397 μm at BL decreased to 264 μm at 4 weeks, to 236 μm at 8 weeks, and to 239 μm at 12 weeks (decreases to BL all statistically significant p < 0.05)., Conclusion: In our cohort, we were able to achieve substantial and significant clinical benefit through ST-LP measured by improvement in BCVA. Furthermore, we were also able to demonstrate measurable, significant morphological improvements as decreased retinal thickness and increased resorption of SRF as probable mechanisms explaining clinical improvement of CSCR with ST-LP. The advantage of ST-LP over other methods is the low risk of adverse events and its high availability. Controlled, randomized studies are necessary to confirm the data and demonstrate the effect over a longer period of time., (© 2021 S. Karger AG, Basel.)

Purpose: To characterize preretinal neovascularizations (NV) and their corresponding branching routes in proliferative diabetic retinopathy (PDR) with optical coherence tomography angiography (OCTA) and compare the findings with fluorescein angiography (FA)., Methods: In patients with PDR, angiograms were acquired with spectral-domain OCTA (CIRRUS 5000, OCTA AngioPlexTMCarl Zeiss Meditec, Inc.) and FA (Zeiss FF450PlusIR fundus camera or Spectralis HRA-OCT SLO, Heidelberg Engineering Inc.) and were consecutively evaluated. Neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) were analyzed with 6 × 6 and 8 × 8 mm OCTA flow images and B-scans with flow registration. Segmentations of the vitreoretinal interface (VRI) and superficial retina were performed for analysis. Two independent investigators examined OCTA findings and compared them to corresponding FA., Results: Forty-two eyes of 30 patients with PDR were analyzed. A total of 76 NV with their corresponding proliferation routes were visualized and characterized, with 55 (72.4%) proliferating along the posterior hyaloid membrane (PHM), 14 (18.4%) along the epiretinal membrane, and 7 (9.2%) along the fibrovascular membrane. The posterior vitreous was partially detached in 37 of 42 eyes (88.1%), completely detached in 1 of 42 eyes (2.4%), and adherent in 1 of 42 eyes (2.4%). In 38 of 42 cases, OCTA was superior (n = 23) or equivalent (n = 15) to FA in detecting NV and provided a more detailed information of the neovascular vessels. In 4 of 42 study eyes, OCTA was inferior to FA., Conclusions: OCTA is a useful tool to detect NV in PDR. In comparison to FA, OCTA has the advantages that it is noninvasive and the image capture takes only seconds. We were able to identify all NV and characterize their corresponding proliferation routes in the VRI, the superficial retina slab, or the B-scan with flow registration. Through evading the masking effect of dye leakage in FA, OCTA is capable of better visualization of NV. FA, however, remains essential for the detection of all NV, since OCTA supplies a smaller detection field. Additionally, we identified the PHM as the main proliferating route of diabetic NV (72.4%), marking it as an important structure for sprouting vessels in neoangiogenesis in PDR., (© 2021 S. Karger AG, Basel.)

Objective: To compare typical findings of diabetic retinopathy in optical coherence tomography angiography (OCTA) and fluorescein angiography (FA)., Subjects/methods: 42 patients were enrolled in this study. We performed FA and obtained en face 3 × 3 mm OCTA images of the macular region. The count of microaneurysms (MAs) and the size of the foveal avascular zone (FAZ) were compared. The assessability of the imaging modalities was graded in each eye., Results: 53 eyes of 42 patients with a mean age of 61 years were included. 36/53 eyes revealed nonproliferative diabetic retinopathy, 17/53 eyes had proliferative diabetic retinopathy. The mean size of the FAZ was 0.39 mm2 in FA and 0.42 mm2 in OCTA. The mean MA count was 14 in FA and 13 in OCTA. The assessability was favorable to OCTA in 38-41/53 eyes regarding the FAZ and favorable to FA in 45-49/53 eyes regarding MAs., Conclusion: We found a good agreement for the size of the FAZ and a weak agreement regarding the count of MAs in both imaging modalities. The readers favored OCTA for the assessment of the FAZ and FA for the assessment of MAs. Complementary use of FA and OCTA ensures the best diagnostic approach in patients with diabetic retinopathy., (© 2019 S. Karger AG, Basel.)

The isozyme protein kinase C (PKC) β is involved in several processes that are deregulated in different retinal cell types by hyperglycemia. This family of serine/threonine-specific protein kinases comprises several different members, which differ in their structure, cofactor requirement and substrate specificity. Therefore, PKCβ was considered a valuable target for therapeutic intervention. However, there is now evidence that even inhibition of different PKC isozymes is not sufficient to normalize vascular endothelial growth factor (VEGF)-induced barrier damage of retinal endothelial cells. On the other hand, PKCβ inhibition prevents hyperglycemia-induced VEGF expression in retinal pericytes, suggesting that PKC inhibitors should be administered before increased VEGF expression is established in the diabetic retina. Although initial studies have indicated that the treatment of diabetic patients with ruboxistaurin, a specific inhibitor of PKCβ, may reduce visual loss in patients with diabetic retinopathy, the overall benefit seems to be small., (© 2016 S. Karger AG, Basel.)

Diabetic retinopathy is one of the major complications of diabetes mellitus and a leading cause of visual loss. Diabetic macular edema (DME) is an ocular manifestation of the disease causing visual deterioration. The prevalence of visual impairment due to DME is estimated to be 5.4% in Europe. Vascular endothelial growth factor (VEGF) is overexpressed in diabetic eyes and plays a key role in the development of DME. VEGF levels were proven to be elevated in the vitreous and retina in patients with diabetic retinopathy. VEGF causes a breakdown of the blood-retinal barrier by influencing the tight junctions of retinal endothelial cells and leading to accumulation of fluid in the macula. Therefore, intravitreal VEGF inhibitors are ideal candidates to treat DME by counteracting VEGF overexpression. This review summarizes the results of the most recent prospective, controlled studies on DME with promising novel VEGF inhibitors. It focuses on the efficacy and safety aspects of anti-VEGF treatment of DME., (Copyright © 2012 S. Karger AG, Basel.)

Ophthalmoscopy, fundus photography and fluorescein angiography are the common tools to diagnose diabetic retinopathy and diabetic macular edema. However, there is an increasing demand for high-resolution imaging of ocular tissues to improve the diagnosis and management of diabetic retinopathy. Optical coherence tomography (OCT) provides important additional information about the retina. It produces reliable, reproducible and objective retinal images especially in diabetic macular edema and provides information about vitreoretinal relationships that can clearly only be detected with OCT. It enhances the ability to exactly diagnose diabetic macular edema, epiretinal membranes, vitreomacular or vitroretinal traction. OCT also brings new insights into morphological changes of the retina in diabetic retinopathy. It demonstrates that macular edema is a complex clinical entity with various morphology. With the OCT, structural changes and quantitative assessment of macular edema have become feasible as determined with retinal thickness and volume. OCT is more sensitive to small changes in retinal thickness than slit-lamp biomicroscopy.

Laser treatment of diabetic retinopathy is still the gold standard of treatment for focal and diffuse diabetic macular edema and proliferative diabetic retinopathy. When properly treated, the 5-year risk of blindness is reduced by 90% in patients with proliferative diabetic retinopathy and the risk of visual loss from macular edema is reduced by 50%. However, only about 35-50% of patients with diabetes mellitus receive regular eye examinations, which are important for timely diagnosis and proper treatment. The necessary goals are better patient education to improve the control of diabetes and better screening programs to reduce the risk of blindness from diabetic retinopathy.

Despite the better options of controlling diabetes mellitus and although the prognosis of diabetic retinopathy has markedly improved by laser treatment and vitreoretinal surgery, diabetic retinopathy still is the leading cause of blindness in working age people in industrialized countries. Little has changed in the last decades regarding the prognosis of ocular complications in diabetes mellitus. We therefore need better tools and new therapeutic approaches for the prevention and treatment of diabetic ocular complications. Newer therapeutic options are directed at the causative mechanisms of diabetic retinopathy. Experimental and clinical evidence suggests that pharmacological compounds like somatostatin analogues and protein kinase C (PKC) inhibitors may be effective in the treatment of diabetic retinopathy. Chronic overproduction of growth hormone and insulin-like growth factor 1 play an important role in the pathogenesis of diabetic retinopathy. In the treatment of diabetic retinopathy somatostatin receptors are the targets of somatostatin analogues like octreotide. Octreotide has shown to be a promising treatment of diabetic retinopathy and diabetic macular edema. One important pathomechanism in the development of diabetic retinopathy is the activation of PKC induced by high glucose due to an increased diacylglycerol level. The selective PKC-beta inhibitor ruboxistaurin mesylate enables a new therapeutical approach for the treatment of diabetic retinopathy. Ongoing prospective clinical trials investigate whether the treatment with the specific PKC-beta inhibitor can prevent the progression of diabetic retinopathy and diabetic macular edema., (Copyright (c) 2007 S. Karger AG, Basel.)

Despite better options of controlling diabetes mellitus and although the prognosis of diabetic retinopathy has markedly improved by laser treatment and vitreoretinal surgery, diabetic retinopathy is still the leading cause of blindness in working-age people in industrialized countries. Little has changed in the last decades concerning the prognosis of ocular complications in diabetes mellitus. Therefore, we need better tools for prevention and treatment of diabetic ocular complications due to diabetic retinopathy that go beyond reduction in glycemia, blood pressure and cholesterol levels. Newer therapeutic options are directed at the causative mechanisms of diabetic retinopathy. Experimental and clinical evidence suggests that pharmacological compounds like protein kinase C subtype Beta (PKC-Beta) inhibitors may be effective in the treatment of diabetic retinopathy. One important pathomechanism in the development of diabetic retinopathy is the activation of PKC induced by high glucose due to an increased diacylglycerol level. The selective PKC-Beta inhibitor ruboxistaurin mesylate enables a new therapeutical approach for the treatment of diabetic retinopathy and diabetic macular edema. Ongoing prospective clinical trials investigate if treatment with the specific PKC-Beta inhibitor ruboxistaurin mesylate can prevent the progression of diabetic retinopathy and diabetic macular edema.

Background: To examine the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and transforming growth factor beta 2 (TGF(beta2)) on bovine retinal pigment epithelial (RPE) cell migration and proliferation., Materials and Methods: Cultured bovine RPE cells were treated with 10 ng/ml PDGF, bFGF, aFGF, IGF-1, EGF, or TGF(beta2). RPE cell migration studies were performed in multiwell plates confluently covered with RPE cells. After inhibition of proliferation and denudation of half of each well, cells were incubated with various growth factors. Migration was measured as the number of cells that had entered the denuded area after 20 h. RPE cell proliferation was determined by [(3)H]thymidine incorporation after growth factor stimulation for 24 h., Results: RPE cell migration was significantly enhanced after incubation with PDGF (stimulation of 213% compared to the negative control, p = 0.002), bFGF (206%, p = 0.003), aFGF (175%, p = 0.003), IGF-1 (150%, p = 0.003), and EGF (144%, p = 0.003). RPE cell proliferation was stimulated by bFGF (322% compared to the negative control, p < 0.005), PDGF (119%, p < 0.005), aFGF (121%, p < 0.005), and EGF (94%, p < 0.005). IGF-1 showed no significant effect on RPE cell proliferation; TGF(beta2) displayed no effect on RPE cell migration nor on proliferation., Conclusions: The peptide growth factors PDGF, bFGF, aFGF, IGF-1, and EGF play an important role in initiating RPE cell migration. Basic FGF, PDGF, aFGF, and EGF stimulate RPE cell DNA synthesis., (Copyright 2004 S. Karger AG, Basel)

Thalidomide and prednisolone were recently introduced as treatment modalities in age-related macular degeneration (AMD). Growth factor-induced activation of retinal pigment epithelial (RPE) cells is a crucial event in this disease. The purpose was to examine the effect of thalidomide and prednisolone on growth factor-preactivated RPE cells. Human RPE cells were stimulated with 10 ng/ml platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), or vascular endothelial growth factor (VEGF) for 24 h. Afterwards, thalidomide (50 microg/ml) or prednisolone (100 ng/ml) were added for 24 h. RPE cell proliferation was determined by [3H]-thymidine incorporation. PDGF and bFGF significantly stimulated human RPE cell proliferation (p < 0.005), the value for VEGF stimulation was not significant (p = 0.3). The effect of the growth factors was diminished after addition of thalidomide and prednisolone (p < 0.005). The current study shows that the inhibitory properties of thalidomide and prednisolone remain even after growth factor activation of the cells., (Copyright 2001 S. Karger AG, Basel)

Purpose: To address the question whether positron emission tomography (PET) can identify malignant ocular tumors., Methods: In patients with ocular tumors, PET was performed using the incorporation of the glucose analogue (18)F-2-fluoro-2-deoxy-D-glucose. The diagnosis of the ocular lesions was based on conventional diagnostic procedures including histologic examination., Results: Nineteen patients with a mean age of 62.8 +/- 14.2 years were included in this study. Nine patients with a mean age of 62.9 +/- 13.1 years displayed the presence of a malignant tumor including metastatic lesions (4), malignant melanomas (4) and squamous cell carcinoma (1). Additionally, 10 patients with a mean age of 62.8 +/- 15.9 years with benign lesions were studied. There was a statistically significant difference (p = 0.012) in tumor height and tumor volume, but not in tumor diameter between benign and malignant lesions. The smallest PET positive lesion measured 7 x 3 mm. PET was positive in 7 out of 9 malignant lesions and negative in all 10 benign lesions, i.e. there was no false-positive and two false-negative results. The two false-negative tumors represented malignant melanomas of the choroid. Additionally, results of the PET examination were independent of tumor size., Conclusion: PET seems to be of limited value for the diagnosis of malignant melanoma of the choroid, i.e. a negative result does not exclude a malignant process., (Copyright 2001 S. Karger AG, Basel)

Background: The retinal pigment epithelium (RPE) has been implicated in the development of diabetic retinopathy and it has been suggested that insulin-like growth factors (IGF) and glucose may be among those factors which are responsible for the RPE changes in diabetics. The purpose of this study was to investigate the effect of IGF-1, IGF-2, and glucose on the migration and proliferation of bovine RPE cells in vitro., Methods: Primary cultures of bovine RPE cells were established from freshly enucleated eyes and passages 5-8 were used for these experiments. RPE cell migration was studied in confluent RPE cultures grown in multiwell plates. After inhibition of proliferation with mitomycin C (10 microg/ml) and partial denudation of the RPE in each well, the cells were incubated with IGF-1 (10 ng/ml), IGF-2 (10 ng/ml) or glucose (10 mM). Migration was measured as the number of cells that had entered the denuded area after 20 h. RPE cell proliferation was determined by [(3)H]-thymidine incorporation after incubation with IGF-1, IGF-2, and glucose for 24 h. Statistical analysis was performed with the paired Student's t test., Results: Exposure of RPE cells to IGF-1, IGF-2, and glucose resulted in a significantly higher RPE cell migration as compared to the control medium (p < 0.008) with 21, 20, 17, and 9 cells/raster field, respectively. Additionally, IGF-1 (p = 0.004) and IGF-2 (p = 0.008) but not glucose caused a statistically significant stimulation of DNA synthesis with 761, 747, and 593 ccpm, respectively, as compared to the negative control (352 ccpm)., Conclusion: This study indicates that IGF-1 and IGF-2 influence RPE cell migration and proliferation. This is further evidence that these factors are among those which have to be kept in mind when trying to modulate the development of diabetic eye diseases., (Copyright 2000 S. Karger AG, Basel)

Purpose: The aim of our study was to describe two different manifestations of retinal pigment epithelial changes associated with systemic corticosteroid treatment., Methods: We report 4 patients who developed maculopathy during treatment with systemic corticosteroids. Additionally, the literature was reviewed for similar cases., Results: Two patients showed diffuse retinal pigment epitheliopathy. Two patients developed central serous chorioretinopathy with localized changes in the retinal pigment epithelium. A review of the literature revealed 51 patients with similar changes during treatment with corticosteroids., Conclusion: These 4 patients provide further evidence that systemic treatment with corticosteroids may cause central serous chorioretinopathy or diffuse retinal pigment epitheliopathy. Ophthalmologic examination is recommended on a regular basis for patients treated with systemic corticosteroids.