Morphometric analyses in patients treated with subthreshold laser photocoagulation for central serous chorioretinopathy.

BACKGROUND AND OBJECTIVE: To analyze changes in selected parameters in optical coherence tomography (OCT) after subthreshold laser coagulation (ST-LP) in patients with central serous chorioretinopathy (CSCR). MATERIALS AND METHODS: Fifty-four eyes of 49 patients with CSCR were included in the study. Each patient underwent therapy with ST-LP with a frequency-doubled Neodym-YAG Laser and OCT imaging. In OCT the thickness of the central subfield, cube volume, average cube thickness, volume under the ETDRS grid, and average thickness under the ETDRS grid were collected. RESULTS: Decreases in total OCT volume and central retinal subfield thickness were statistically significant (p < 0.05). Possible correlations were observed between visual acuity at V3 (3 months after ST-LP) and Baseline and between central retinal subfield thickness at V1 (4 weeks after ST-LP) and visual acuity at BL. CONCLUSION: A decrease in retinal thickness and retinal volume could be shown after ST-LP. Central retinal subfield thickness measured by OCT could be a more sensitive measure than mean retinal thickness or macular volume for early detection of disease recurrence occurring in some patients 3 months after ST-LP.

[New Possibilities in Retinal Diagnostics Using OCT Angiography]. / Neue Möglichkeiten in der retinalen Diagnostik mittels OCT-Angiografie.

BACKGROUND: Instruments for using OCT angiography (OCTA) in daily clinical practice have recently become available. The aim of this paper is to report the possibilities, advantages and limitations of OCTA in the clinical diagnosis of diseases of the posterior segment of the eye. PATIENTS/METHODS: Patients with diabetic retinopathy, retinal vascular occlusions, and age-related macular degeneration who had been assigned to fluorescein angiography (FA) additionally underwent an AngioPlex™-OCTA examination, which captures a 6 × 6 mm scanning area centred on the fovea. If deemed necessary, 3 × 3 mm volume scans were created in regions of interest. The findings of FA and OCTA were correlated and compared. RESULTS: The OCTA procedure took only a few seconds, was easily integrated into the standard OCT diagnostic imaging procedure, and delivered highly detailed, three dimensional images of the entire microvasculature of the retina and choroid. Microvascular changes, such as microaneurysms, intraretinal microvascular abnormalities, non-perfused areas, alterations in the foveal avascular zone (FAZ) and neovascularization were reliably detected. Overall, OCTA results were in good agreement with the results of the FA. Additionally, OCTA provided more detailed and three dimensional information and thus permitted a better assessment of the spatial extension of microvascular abnormalities. Due to OCTA's limited scanning area, vascular alterations in the mid-periphery were detected only if their location had already been determined by FA. Although OCTA does not show leakage, macular oedema can be diagnosed from OCTA, together with OCT thickness measurements. CONCLUSION: OCTA provides important three dimensional information on vascular alterations and is already an indispensable diagnostic method. As the procedure takes just a few seconds and can be performed non-invasively, OCTA is well suited as a monitoring method and may allow early diagnosis. In this sense, prospective studies are required to determine precise OCTA analytical strategies for specific diseases. It is very likely that OCTA will revolutionise the diagnosis of retinal and choroidal diseases; however, it is not yet clear estimated to what extent it will replace FA.

[Ophthalmoscopy in the era of optical coherence tomography]. / Ophthalmoskopie im Zeitalter der optischen Kohärenztomographie.

For more than one and a half centuries ophthalmoscopy has been the main diagnostic procedure in ophthalmology for diagnosing retinal diseases. The techniques have improved over the years and ophthalmoscopy is still the gold standard for all retinal diseases, especially for peripheral retinal diseases. The introduction of optical coherence tomography (OCT) has revolutionized ocular diagnostics of macular diseases as OCT is able to detect retinal changes that cannot be diagnosed as well with ophthalmoscopy alone. Nevertheless, diagnosis of a retinal disease should not be made on the basis of OCT findings alone but always in combination with ophthalmoscopy. If necessary further diagnostic procedures should be added to improve the accuracy of diagnosis, to follow the course of the disease and to control the success of treatment.

[Basic in vitro studies on VEGF inhibition with aflibercept: similarities and differences to other VEGF-binding therapeutic proteins]. / Grundlegende In-vitro-Untersuchungen zur VEGF-Inhibition mit Aflibercept: Gemeinsamkeiten und Unterschiede zu anderen VEGF-bindenden therapeutischen Proteinen.

Patients suffering from various retinal diseases benefit from therapies directed against the vascular endothelial growth factor (VEGF). Aflibercept (Eylea) is another VEGF-binding protein available for intravitreal injection, in addition to the antibody bevacizumab (Avastin) and the F(ab) fragment ranibizumab (Lucentis). Aflibercept's distinct structure and broader binding specificity may have clinically relevant consequences, which is supported by basic in vitro studies and observations in animal eyes. All pathological processes involving neovascularisation are driven by the dominant action of VEGF, but other factors including placenta growth factor (PlGF), a mitogenic protein for retinal endothelial cells, potentially modulate its effects. Aflibercept is an inhibitor of both VEGF and PlGF and therefore may have superior therapeutic effects in some cases. However, whether or not aflibercept's broader binding specificity or different affinities for the different VEGF-binding proteins to VEGF result in substantially diverse therapeutic efficiencies has not yet been clarified. In vitro studies confirm that aflibercept efficiently prevents or normalises VEGF-stimulation of retinal cells and disturbance of their barrier function. These experiments also show that aflibercept is taken up by important retinal cell types and affects their normal function, i.e., migration of endothelial cells and phagocytosis of pigment epithelial cells. In accordance with a role of the Fc domains of aflibercept and bevacizumab, substantial amounts of both proteins are internalised, whereas only a small portion of ranibizumab enters the cells. Internalisation and storage by ocular cells, also observed in vivo after intravitreal injection into eyes of monkeys, may result in not yet recognised side effects during long-term treatment of patients with certain VEGF-binding proteins.

[Treatment of diabetic macular oedema with the VEGF inhibitors ranibizumab and bevacizumab: conclusions from basic in vitro studies]. / Therapie des diabetischen Makulaödems mit den VEGF-Inhibitoren Ranibizumab und Bevacizumab: Schlüsse aus grundlegenden In-vitro-Untersuchungen.

Diabetic macular oedema (DMO) which may occur at all stages of diabetic retinopathy (DR) is a severe vision-threatening complication. In most cases, laser treatment does not improve visual acuity. Therefore research in ophthalmology focuses on the improvement of the prognosis of DMO patients with a drug-based DMO therapy. Vascular endothelial growth factor (VEGF) is considered the most important therapeutic target because this growth factor also is the most potent permeability factor affecting the inner retinal barrier formed by endothelial cells (ECs). Compared to its angiogenic stimulation of proliferation and migration of ECs, effects of VEGF on permeability have not been studied in all details. In vitro investigations on the behaviour of primary or immortalised retinal endothelial cells confirmed the key role of VEGF in the regulation of the permeability of the inner retinal barrier. Despite the presence of a variety of other factors found to be elevated in DR, a VEGF-disrupted barrier can be completely restored with the VEGF-inhibiting ranibizumab (Lucentis®) and bevacizumab (Avastin®) when applied at clinically achievable concentrations. The antibody bevacizumab, but not the antibody fragment ranibizumab, accumulates in both retinal EC and pigment epithelial cells during prolonged treatment. This observation might be relevant because patients are often treated for several years and additional long-term side effects may be recognised in the future.

[Mechanisms of retinal neurodegeneration as a result of diabetes mellitus]. / Mechanismen retinaler Neurodegeneration als Folge von Diabetes mellitus.

Diabetic retinopathy is characterised by microvascular damage to the retina caused by diabetes mellitus. Early vascular findings are microaneurysms and a breakdown of the blood-retina barrier. Recent studies indicate that neurodegeneration and neuroinflammation of the retina play an important role in the pathogenesis of diabetic retinal changes. They can occur early and preceed vascular changes. Important features of neurodegeneration of the retina are apoptosis and glia activation. This results in the loss of neuroretinal tissue.

New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel.

The current standard therapy for patients with diabetic macular oedema (DME)--focal/grid laser photocoagulation--usually does not improve impaired vision, and many patients lose vision despite laser therapy. Recent approval of ranibizumab by the European Medicines Agency to treat visual impairment due to DME fulfils the previously unmet medical need for a treatment that can improve visual acuity (VA) in these patients. We reviewed 1- and 2-year clinical trial findings for ranibizumab used as treatment for DME to formulate evidence-based treatment recommendations in the context of this new therapy. DME with or without visual impairment should be considered for treatment when it fulfils the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria for clinically significant oedema. For DME with centre involvement and associated vision loss due to DME, monthly ranibizumab monotherapy with treatment interruption and re-initiation based on VA stability is recommended. Laser therapy based on ETDRS guidelines is recommended for other forms of clinically significant DME without centre involvement or when no vision loss has occurred, despite centre involvement. Because these recommendations are based on randomised controlled trials of 1-2 years duration, guidance may need updating as long-term ranibizumab data become available and as additional therapeutic agents are assessed in clinical trials.

[Ocular findings in hematological diseases]. / Augenveränderungen bei hämatologischen Erkrankungen.

Hematological diseases can lead to ocular manifestations in up to 90% of patients and sometimes the ophthalmological findings are the presenting symptom of the disease. The ocular manifestation is often asymptomatic. The diagnosis can be difficult especially when the ocular manifestation represents the first symptoms. In most cases the conjunctiva and retina are involved and are particularly found in patients with anemia, leukemia, Hodgkin and non-Hodgkin lymphoma, myeloproliferative and myelodysplastic syndromes and coagulopathies. Even opportunistic infections in cases of hematological diseases can lead to ocular manifestations. For unexplained retinal alterations with hemorrhage and cotton-wool spots an underlying hematological disease should be excluded.

[New developments in the pharmacological treatment of macular oedema due to retinal vein occlusion]. / Neue Entwicklungen in der pharmakologischen Therapie des Makulaödems bei retinalen Venenverschlüssen.

The therapeutic options for retinal vascular diseases have changed due to new study results and the approval of dexamethasone (Ozurdex®) and ranibizumab (Lucentis®) by the EU commission for visual loss caused by macular oedema in retinal vein occlusion. In addition to laser treatment, we have now two approved drugs for the treatment of macular oedema. Therefore it is important to make decisions about the best treatment in retinal vein occlusion. This necessitates knowledge of the posology of the drug and assessment of the advantages and risks of the different treatment modalities. Therefore it is important to know the efficacy and safety data of the different therapies. The approval of dexamethasone and ranibicumab for the treatment of macular oedema in branch and central retinal vein occlusions improves the chances for the outcome, especially concerning visual acuity. The new results from the dexamethasone and ranibizumab studies in matters of efficacy and safety and treatment recommendations are described.

[Photocoagulation of age-related juxtapapillary choroidal neovascularisation]. / Lasertherapie der altersbezogenen juxtapapillären chorioidalen Neovaskularisation.

BACKGROUND: The aim of this study was to evaluate retrospectively the clinical outcome of retinal photocoagulation of age-related juxtapapillary choroidal neovascularisation (CNV) with macular oedema. Juxtapapillary CNV represents a rare form of extrafoveal CNV in age-related macular degeneration (AMD). PATIENTS AND METHODS: In 15 eyes of 14 patients with age-related juxtapapillary choroidal neovascularisation, CNV was treated with several rows of frequency doubled Nd:YAG laser (532 nm) irradiation to protect the fovea. Classification of the CNV was performed with fluorescein angiography. Best corrected visual acuity was determined before and after photocoagulation. Follow-up time was 1 - 32 months. RESULTS: In 13 eyes the juxtapapillary CNV was occult (87 %), one eye had a classic, one eye a minimally classic form. In 13 eyes (87 %) the centre of the fovea showed macular oedema in spite of the extrafoveal location of the CNV. Of these 13 eyes, in 10 eyes (77 %) visual acuity increased after photocoagulation. 7 eyes (53 %) had an increase in visual acuity of 1 or 2 lines, 3 eyes of ≥ 4 lines. 2 eyes showed a stable visual acuity, in 1 eye visual acuity deteriorated after photocoagulation. In 2 eyes without foveal involvement of macular oedema, CNV was located in the papillo-macular bundle and threatened the centre of the fovea. Postoperative visual acuity in theses eyes was stable after 1 and 5 months. CONCLUSION: The therapeutic benefit of photocoagulation of juxta- and extrafoveal classic CNV has already been proven. According to our results, photocoagulation is an effective therapeutic approach in the treatment of age-related juxtapapillary CNV especially, in the occult form, when the fovea is threatened by or involved in the macular oedema.

[Rare ocular manifestation of Horton's disease]. / Seltene okuläre Manifestationen bei Morbus Horton.

BACKGROUND: Ocular manifestations of giant cell arteritis are anterior ischaemic optic neuropathy (AION) or retinal vessel occlusion. Rarely, it can also cause choroidal infarction or tonic pupil. METHODS: Five patients with the diagnosis of giant cell arteritis and rare ocular manifestations are described. The analysis comprises: age, sex, best corrected visual acuity, anterior eye segment, fundus findings, fluorescein angiography (FAG), C-reactive protein, erythrocyte sedimentation rate and biopsy of the temporal artery. RESULTS: The age ranged from 71 to 82 years (median: 76.5), sex distribution f : m = 4 : 1. The visual acuity was between light perception and 1 / 7.5 (median: 1 / 15 LT) on first examination and between light perception and 0.4 (median: 0.3) after therapy. 4 / 5 patients revealed chorioidal ischaemia combined with an AION, an atypical central-arterial-occlusion or a branch retinal artery occlusion on FAG. 1 / 5 showed an anterior ischaemia with corneal oedema, anterior chamber inflammation and pupillotonia, but without involvement of the fundus. The patients had typical symptoms for Horton's disease, such as headache, jaw claudication and weight loss. At first examination, the C-reactive protein was 17.8 - 144 mg/L (median: 76) and the ESR was 28 - 92 mm/h (median: 83.5). After mega dose therapy with decortin H (500 mg/day) i. v. for 3 days and then slowly tapering from 1 mg/kg BW orally the CRP decreased to 1.8 - 50 mg/L (median: 113) and the ESR to 1 - 30 mm/h (median: 15). The diagnosis of giant cell arteritis was proven in 3 / 5 cases with a biopsy of the temporal artery, two patients refused the biopsy. CONCLUSIONS: There are different ocular manifestations of giant cell arteritis. In rare cases it can cause an ischaemia of the anterior eye segment or chorioidal infarctions. Especially in combined occlusions of the retinal and choroidal vessels with AION or tonic pupil Horton's disease must be ruled out because of the high risk of blindness in one or even both eyes. Therefore early diagnosis and treatment of giant cell arteritis is important.

[Objective measurement of macular optical density]. / Möglichkeiten der objektiven Messung der optischen Dichte der Makula.

Determination of the optical density of the macular pigment may be used for an assessment of the efficacy of oral lutein supplementation in patients with dry AMD. Beside subjective methods like heterochrome flicker photometry, objective methods like the 2-wavelength auto-fluorescence method and the 1-wavelength reflection method are in clinical use today. Both methods show comparable results. For a long-term assessment of the efficacy of oral lutein supplementation, different parameters like mean and maximal optical density as well as the integral over optical density on all pixels ("volume") should be used. The parameter volume often increases also in cases in which other parameters do not change anymore. The 1-wavelength reflection method is used for the newly initiated LUTEGA study. This study will investigate the long-term effects of a fixed lutein/omega-3-fatty acid combination on the optical density in patients with dry AMD.

[Photodynamic therapy with verteporfin in occult choroidal neovascularization in age-related macular degeneration]. / Photodynamische Therapie mit Verteporfin bei okkulter chorioidaler Neovaskularisation im Rahmen der altersbezogenen Makuladegeneration.

OBJECTIVE: We investigated retrospectively the clinical outcome of photodynamic therapy (PDT) with verteporfin (Visudyne) in patients with exudative age-related macular degeneration (ARMD) and subfoveal occult choroidal neovascularization (OCN). METHODS: 77 consecutive patients (90 eyes) with OCN were retrospectively analysed using a standardised protocol. It included best corrected visual acuity (BCVA) pre- and post-PDT, greatest linear dimension of OCN (GLD), ophthalmoscopic findings, optical coherence tomography (OCT), fundus photography and fluorescein angiography (FAG). The findings were descriptively analysed by Spearman rank correlation and cross-tabulation. RESULTS: Age ranged from 52 to 92 years (median: 79 years). 7 (8 %) of 90 PDT eyes gained > or = 2 lines, 67 (74 %) eyes stabilised with +/- 1 line. 17 eyes (18 %) showed a deterioration with loss of > or = 2 lines. BCVA of all cases was pre-PDT 0.33 (+/- 0.2), post-PDT 0.27 (+/- 0.2, p < 0.05), in the improvement group pre-PDT 0.4, post-PDT 0.7 in the stable cases pre-/post-PDT 0.3 and in the deterioration group pre-PDT 0.4 and post-PDT 0.2. GLD of all cases was pre-PDT 3.91 mm (minimum: 0.76 mm, maximum: 5.43 mm). From 86 eyes with OCT follow-up of at least 3 months 51 (60 %) had dry macula after last PDT and 35 (40 %) persistent macular edema (ME) in OCT. In 21 eyes (23 %) with leakage of fluorescein after last PDT, treatment was terminated. 10 eyes (47 %) had retinal angiomatous proliferation stage III, of these, 6 eyes presented with retinochoroidal anastomoses. 4 eyes (18 %) showed after PDT retinochoroidal anastomoses, 2 (10 %) vitreomacular traction in epiretinal membrane of the macula, 2 (10 %) had a tear of the retinal pigment epithelium, 1 (5 %) eye had a gain of GLD > 7200 microm, in 1 eye (5 %) BCVA was < 0.05 and in 1 eye (5 %) treatment was stopped at request of the patient. CONCLUSIONS: According to our study PDT might be helpful in the treatment of OCN in ARMD patients for stabilisation but not for improvement of BCVA. Results from large multicentre studies show that concerning BCVA ranibizumab (Lucentis) is superior to PDT in OCN. Further studies are required to investigate the outcome of combined therapy with PDT and VEGF inhibitors for reducing the number of treatments or the number of recurrences of choroidal neovascularisation.