[Acute, bilateral visual loss in a patient with IgA glomerulonephritis]. / Akute, bilaterale Visusminderung bei einem Patienten mit IgA-Glomerulonephritis.

We report on a 30-year-old male patient presenting with acute bilateral loss of vision. Fundus examination showed bilateral retinal hemorrhages, cotton-wool spots, macular edema and optic disk hyperemia. The blood pressure was elevated. The patient was referred to the emergency department with the diagnosis of severe stage IV hypertensive retinopathy. Further examination revealed a previously unknown IgA glomerulonephritis with terminal renal failure and secondary blood pressure derailment. Hypertensive retinopathy can be a first sign of acute renal failure. In cases of hypertensive retinopathy the differential diagnosis including systematic screening is of utmost importance.

[Thickening or hypoplasia of the fovea]. / Verdickung oder Hypoplasie der Fovea.

A 64-year-old female patient complained of a bilateral reduction in vision. The foveal reflex was remarkable bilaterally and optical coherence tomography (OCT) demonstrated the absence of a foveal depression. After exclusion of possible diseases foveal hypoplasia was diagnosed. This rare alteration of the fovea should not be mistaken for foveal edema. A volume scan with a narrow grid is advisable to avoid a misinterpretation.

[Diabetic maculopathy. Diagnosis and treatment]. / Diabetische Makulopathie : Diagnose und Behandlung.

Due to demographic change the incidence of diabetic retinopathy has risen in spite of new facilities and prevention campaigns and is still one of the leading causes of blindness in Germany. The combination of focal/grid laser photocoagulation and an intravitreal anti-VEGF (vascular endothelial growth factor) regimen is the first line approach for clinically significant macular edema with foveal involvement and is evidence-based. Vitreomacular interface abnormalities can be effectively treated by modern vitreomacular surgery. Unfortunately, no proven treatment modality can be provided for ischemic maculopathy. The management of systemic risks factors, such as hyperglycemia and arterial hypertension, remains a task of great importance despite all modifications and increase of knowledge during recent years. Innovative developments in the field of intravitreal pharmacotherapy have opened up new vistas. There are good prospects that modern ophthalmology will not be limited to preserving visual function but to allow improvements and consequently enhance health-related quality of life for diabetic patients.

[Macular translocation - a therapeutic approach for neovascular macular degeneration in the era of anti-VEGF therapy?]. / Makulatranslokation - eine Therapie der neovaskuläre Makuladegeneration im Zeitalter der Anti-VEGF-Therapie?

Since anti-VEGF treatment has been proven to achieve a significant improvement of visual acuity in a cohort of patients with neovascular age-related macular degeneration (AMD), macular surgery and particularly the macular translocation with 360 degrees retinotomy (FMT: full macular translocation) have lost their former popularity. However, the approach of macular surgery still remains a promising therapy in selected cases. A prospective randomised study, comparing FMT and photodynamic therapy in subfoveal classic choroidal neovascularisation (CNV), recently showed the superiority of FMT in terms of visual gain. In spite of the postoperative complications and the disturbed binocular vision, the reading acuity and the life quality of many patients improved. Therefore, it is justified to discuss the chances and advantages of the FMT at least in selected cases. After all, case selection was an important determinant also in the phase III studies of ranibizumab; many patients seen during the routine consulting hours were excluded as a consequence of the study criteria. Most of them were suspected to achieve a less favourable outcome of the anti-VEGF regimen. Thus, patients who did not meet the inclusion criteria of recent studies or showed no response to the anti-VEGF therapy, as well as patients with extensive submacular bleeding or ruptures of the pigment epithelium can also be considered as candidates of FMT. Generally, in the presence of highly effective anti-VEGF drugs, FMT can be discussed for second-line treatment, if the fellow eye has poor function and no additional risk factors of the affected eye are known (e. g., hyperopia, large lesion size, etc). Detailed information relating to the potential adverse events have to be mentioned. Although the indication is restricted, surgeons should have the continuing ability to perform the challenging surgical procedure.

[Neovascular age-related macular degeneration in Germany. Encroachment on the quality of life and the financial implications]. / Neovaskuläre altersabhängige Makuladegeneration in Deutschland. Beinträchtigung der Lebensqualität und ihre finanziellen Auswirkungen.

BACKGROUND: Approximately 35,000 cases of neovascular age-related macular degeneration (AMD) occur annually in Germany. The neovascular form of AMD (NV-AMD) is responsible for severe vision loss associated with the disease in 90% of the cases. This study was conducted to assess the humanistic and economic burden of NV-AMD in the German population. METHODS: A cross-sectional, observational study of subject self-reported functional health, well-being, and disease burden among elderly subjects with (n=83) and without (n=93) NV-AMD in Germany was conducted. Patients participated in telephone surveys involving the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and also reported history of falls, fractures, and healthcare resource utilization. Furthermore, the healthcare utilization and unit costs for the NV-AMD patients were calculated. RESULTS: The mean age of NV-AMD patients was 77.2 years and 64% were female. NV-AMD patients reported significantly worse vision-related function and overall well-being than controls (adjusted mean scores: NEI-VFQ-25 overall scale: 51.3 vs 96.3; p<0.0001) and significantly more depression symptoms than controls (HADS depression: 6.2 vs. 2.7; p<0.0001). NV-AMD patients also reported that the need for assistance with daily activities was more than 10 times greater compared to controls (26.5% vs. 2.2%; p<0.0001) and the prevalence of falls was 3 times that of the control group (13.3% vs 4.3%; p=0.031). Annual NV-AMD costs per patient were 9871, 6 times that of elderly patients without NV-AMD ( 1559). Of the NV-AMD costs one-half were direct non-medical-related costs (assistance of ADL or social benefit) and one-third were direct medical costs. CONCLUSIONS: NV-AMD is associated with decreased functional abilities and quality of life, which result in an increase in healthcare resource utilization. Consequently, costs were higher for NV-AMD patients compared to controls. These findings emphasize the need for new NV-AMD treatments that will prevent vision loss and progression to blindness, and lessen the ensuing economic burden. Sponsored by Pfizer Inc. New York, US.

Treatment of chronic ocular hypotony with intraocular application of sodium hyaluronate.

AIM: The aim of the study was to report the functional and morphological outcome of intraocular injection of sodium hyaluronate for treatment of chronic ocular hypotony (COH). METHODS: We reviewed the digital chart records of patients with COH who had received one or more injections of intravitreal or intracameral sodium hyaluronate (1.4% or 2.3%). The changes in the best corrected visual acuity (BCVA) and intraocular pressure (IOP) after treatment were recorded. RESULTS: Thirty-two eyes of 32 patients with a mean age of 56.8 years were analysed. Previous vitreoretinal surgery had been performed on all eyes for either ocular-penetrating trauma (six eyes), chronic uveitis (six eyes), full macular translocation (five eyes) or retinal detachment (15 eyes). Mean follow-up time after the first intraocular injection was 29.7 months. BCVA (logMAR) at the baseline and the last follow-up visit were 1.84 (SE 0.65) and 1.82 (SE 0.72), respectively (p = 0.87). The mean IOP at the baseline increased from 2.28 (SE 0.27) mmHg to 7.12 (SE 1.03) mmHg at the last visit (p<0.001). At the final follow-up, 20 eyes (62.5%) had an IOP higher than 5 mmHg and 24 eyes (75%) had an unchanged or improved BCVA. CONCLUSIONS: Stabilisation of the IOP and vision in some eyes with COH following vitreoretinal surgery can be achieved with intraocular injection of sodium hyaluronate. Large case-series and long-term follow-up are necessary to confirm the beneficial role of intraocular sodium hyaluronate injections in such eyes.

Retinal pigment epithelial tears after single administration of intravitreal bevacizumab for neovascular age-related macular degeneration.

PURPOSE: To analyse retinal pigment epithelial (RPE) tears following single administration of intravitreal bevacizumab for neovascular age-related macular degeneration (AMD) during early follow-up. METHODS: Interventional, retrospective, non-comparative case series included 397 patients (409 eyes) of the 746 consecutive patients that met the eligibility criteria. Standardized visual acuity testing, fluorescein angiography, and optical coherence tomography were performed. Data collected included status of the fellow eye, previous treatment, subtypes of choroidal neovascularization (CNV), size and composition of the lesion. Multiple linear regression modelling was used to explore the effect of baseline parameters on the RPE tears. Primary end point was occurrence of RPE tears within 6 weeks after therapy. RESULTS: Fifteen of the 409 eyes (3.6%) developed RPE tear (95% confidence interval: 2.2-6.0, odds ratio: 26.3). The statistical modelling showed significant association between RPE tear and occult without classic CNV/predominantly haemorrhage vspredominantly/minimal classic CNV (P=0.019), as well as medium or large (>4 disc area) vssmall size of the total lesion (P=0.038). Previous treatment and status of the fellow eye did not statistically influence the risk of RPE tears. CONCLUSIONS: An RPE tear can develop in up to 3.6% of eyes with neovascular AMD following single administration of intravitreal bevacizumab in a short-term follow-up. Medium and large lesion size and occult without classic and predominantly haemorrhagic subtype of CNV were important predictive factors. Preoperative assessment of the lesion characteristics may help in identifying the risk of individual patients with neovascular AMD before intravitreal bevacizumab treatment.

[Asteroid hyalosis within an epiretinal membrane]. / Asteroide Hyalose in einer epiretinalen Membran.

CASE REPORT: In May 2007 an 80-year-old man with a known proliferative diabetic retinopathy presented in our outpatient department with a decrease in visual acuity of his right eye. There was a thick asteroid hyalosis preventing fundus examination. Sonographically, there were vitreoretinal tractions requiring a vitrectomy. During surgery an epipapillary membrane was removed. RESULTS: Microscopically round amorphous bodies were conspicuous which were slightly basophilic in the H&E stain. The amorphous bodies were strongly positive in the periodic acid-Schiff staining. They were embedded in a fibrovascular stroma and partly surrounded by inflammatory cells with numerous giant cells of foreign body reaction. CONCLUSION: Asteroid hyalosis is a common degenerative disorder in the vitreous body. The aetiology and the pathogenesis of the asteroid bodies are not yet fully understood. An association of asteroid hyalosis with systemic diseases like diabetes mellitus, arterial hypertension, hyperlidpidaemia and atherosclerotic vasculopathy is postulated. Normally, therapy for an asymptomatic asteroid hyalosis is not necessary. The tractive proliferative diabetic retinopathy in our patient did require surgery. The incorporation of hyaloid bodies into an epiretinal membrane with the induction of a foreign body reaction is unusual.

Can the risk of retinal pigment epithelium tears after bevacizumab treatment be predicted? An optical coherence tomography study.

BACKGROUND: Retinal pigment epithelium (RPE) tears after bevacizumab treatment for neovascular age-related macular degeneration accompanied by a pigment epithelial detachment (PED) might be caused by stretching forces on the already weakened RPE. The purpose of this study was to evaluate whether simple measurements of optical coherence tomography (OCT) can predict the individual risk of an RPE tear in preoperative candidates. METHODS: A retrospective chart review study of 393 consecutive patients with neovascular age-related macular degeneration evaluated OCT images (Stratus-OCT Zeiss, Jena, Germany). The height of the PED, the central retinal thickness, and the maximum retinal thickness were determined by two independent observers and retrospectively analysed. RESULTS: Fifteen patients with an RPE tear had a significant higher PED than the remaining study population. In contrast, no correlation was seen with the central retinal thickness. In a linear regression model, the probability of an RPE tear exponentially increased in dependence of the extent of PED. CONCLUSION: The risk of an RPE tear can be estimated by simple measurement of the height of the PED on OCT.

Full macular translocation following photodynamic therapy in neovascular age-related macular degeneration.

PURPOSE: To report the long-term functional and anatomical outcome of full macular translocation (FMT) in eyes with neovascular age-related macular degeneration (AMD) following photodynamic therapy (PDT). METHODS: Twelve eyes of 12 consecutive patients with neovascular AMD who were PDT-nonresponders and underwent FMT were analysed. Best-corrected visual acuity (BCVA) measurement, fundus photography, and fluorescein angiography at baseline and at follow-up examinations in 3 months intervals were performed. Primary end point was change of BCVA from baseline to last visit. RESULTS: Totally 12 eyes of 12 patients were analysed. Mean time interval between the last PDT and FMT was 3.7 months (range 1-10 months). Mean follow-up after FMT was 25.6 months. BCVA ranged at baseline from 20/1000 to 20/80 (mean 20/230). At the last visit, mean BCVA was by 20/185. BCVA improved in 50% (6/12) of eyes by more than 1 line. Twenty five per cent (3/12) of eyes had final BCVA within +/-1 line from baseline. In 25% (3/12) of eyes the BCVA decreased by more than 1 line. One eye had recurrent CNV. In four eyes a cystoid macular oedema developed. No retinal detachment or disturbing diplopia was noted. CONCLUSIONS: In the present study, FMT in PDT-nonresponders stabilised or improved visual acuity in the majority of the eyes in a mean follow-up period of nearly 2 years. FMT can be considered as a therapeutical option in eyes who are nonresponders to the PDT in neovascular AMD.

Surgical treatment of peripapillary choroidal neovascularisation.

OBJECTIVE: To report the functional and morphological outcome of surgical treatment of peripapillary choroidal neovascularisation due to age-related macular degeneration. METHODS: Consecutive interventional case series of eight patients with extensive peripapillary choroidal neovascularisation and accompanying haemorrhage who underwent subretinal surgery including extraction of the neovascular complex. Ophthalmic examination, including visual acuity testing, colour photography and fluorescein angiography, was performed at baseline and at 3, 6, 9 and 12 months, and then yearly. RESULTS: Mean follow-up was 26 months (12-60 months). Preoperative best corrected visual acuity (BCVA) ranged from logMAR (logarithm of minimum angle of acuity) 1.0 (20/200) to logMAR 0.0 (20/20), with a mean of logMAR 0.5 (20/63). Mean postoperative BCVA was logMAR 0.3 (20/40). BCVA improved in six patients, was stable in one patient and deteriorated in one patient. Two years after surgery, one patient developed recurrence of the CNV that was removed surgically. One patient showed retinal detachment 5 years after subretinal surgery. CONCLUSIONS: In this small case series of PPCNV, functional improvement was achieved after surgery in the majority of patients. Surgical extraction of the CNV represents an alternative treatment option in eyes with vision-threatening extensive PPCNV. Randomised controlled studies seem to be justified to evaluate further the beneficial effect and long-term functional outcome of this therapy approach.

Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration.

BACKGROUND: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. METHODS: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. RESULTS: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). CONCLUSIONS: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

[Bevacizumab for treatment of macular edema secondary to retinal vein occlusion]. / Bevacizumab zur Therapie des sekundären Makulaödems nach venösen Gefässverschlüssen.

Application of VEGF inhibitors represents a treatment option for macular edema secondary to retinal vein occlusion that targets the disease at the causal molecular level. First reports on intravitreal injections of bevacizumab show promising morphological and functional effects and demonstrate that bevacizumab is a potent antiedematous agent in this context. A significant reduction of the central retinal thickness followed by a rapid improvement of visual acuity may be achieved within days. In a pilot study with a review period of 3 months, we found a significant improvement of one or more lines in 93% and four or more lines in 27% of eyes. This was associated with a concomitant significant reduction in central retinal thickness, which, however, was not sustained by a single injection (64% reduction after 1 month and 28% after 3 months). No relevant adverse events were noted. The duration of action after intravitreal bevacizumab administration is currently unknown. Reinjections will be necessary to maintain a lasting beneficial effect. Prospective, controlled long-term studies are mandatory to develop standardized treatment protocols that allow a safe and effective application of this off-label therapy.

Effects of bevacizumab on retinal function in isolated vertebrate retina.

BACKGROUND: Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application. METHODS: Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings. RESULTS: During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged. CONCLUSION: The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.

Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular membranes.

AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age related macular degeneration. METHODS: Retrospective review of 22 surgically excised CNV. 12 of these patients had been treated with PDT 3-146 days previously. Apoptotic cells were detected with the TUNEL technique and compared to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised both by collapsed and patent vessels. The EC displayed a statistical significant positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001) and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV excised 1-5 months after PDT displayed a patent vascularisation and high proliferative activity. All membranes either treated or untreated disclosed only sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS: Verteporfin PDT leads to selective and effective damage of EC within CNV. Both patent and occluded vessels were lined by apoptotic EC. This finding and the increased expression of proliferation marker at later time points suggest that revascularisation after PDT is caused by angiogenesis rather than recanalisation.