Stefan Dithmar

Intravitreal bevacizumab for treatment of chronic central serous chorioretinopathy

Purpose To evaluate the short-term safety and efficacy of intravitreal bevacizumab for the treatment of intraretinal or subretinal fluid accumulation secondary to chronic central serous chorioretinopathy (CSC). Methods Twelve patients were treated with intravitreal injections of 2.5 mg bevacizumab at 6-to 8-week intervals until intraretinal or subretinal fluid resolved. Observation procedures were Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), ophthalmic examination, and optical coherence tomography (OCT), performed at 6- to 8-week intervals. Fluorescein angiography was performed at baseline visit and thereafter depending on clinical and OCT findings. Multivariate analysis of variance with repeated measures was used to calculate a statistical significance of change in BCVA and mean central retinal thickness, which were the main outcome measures. SAS statistical software was used for analyses. Results Patients received 2±1 intravitreal injections of bevacizumab on average during a follow-up of 24±14 weeks. Mean BCVA increased by 2±2 lines; the change in BCVA (log-MAR) was significant (p<0.02). Mean central retinal thickness decreased significantly over follow-up (p<0.05), with 6 patients (50%) showing complete resolution of subretinal fluid. Conclusions Anatomic and functional improvement following intravitreal bevacizumab injections suggest that vascular endothelial growth factor (VEGF) may be involved in fluid leakage in patients with chronic CSC. The results suggest a possible role for anti-VEGF agents in the treatment of chronic CSC. Further evaluation of intravitreal bevacizumab for chronic CSC in controlled randomized studies is warranted.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

Digital simultaneous fluorescein and indocyanine green angiography, autofluorescence, and red-free imaging with a solid-state laser-based confocal scanning laser ophthalmoscope.

Purpose: To describe and to evaluate a novel confocal scanning laser ophthalmoscope (cSLO) for fluorescence angiography, fundus autofluorescence (FAF), and red-free imaging. Methods: Digital infrared, red-free, FAF, fluorescein, and indocyanine green (ICG) angiography images were obtained with a cSLO in 766 patients. An optically pumped solid-state laser generates the excitation wavelength (488 nm) required for red-free, FAF, and fluorescein angiography images. For ICG angiography and infrared imaging, diode laser sources at 790 and 820 nm are used. Further features include an internal fixation control and a focus range of −24 to +30 diopters. Results: High-image quality is achieved with a resolution of up to 5 &mgr;m per pixel in 30- x 30-degree images and allows for accurate delineation of normal and pathologic features. Simultaneous angiography offers high-contrast images. Corresponding display of quasi-simultaneous frames facilitates interpretation. A small focus difference between fluorescein and ICG scans occurs because of chromatic aberrations. Automated alignment and generation of mean images from several single frames allow for acquisition of high-resolution FAF images. Conclusion: Various laser-source related, optical, and electronic innovations improve cSLO fundus imaging for routine clinical application. A solid-state laser has advantages compared to argon gas laser sources, including less space occupation, heat emission, and noise production.

Intraocular Melanoma Spread To Regional Lymph Nodes: Report of Two Cases

Purpose: To report two cases of regional lymphatic spread of primary uveal melanoma. Methods: The clinical records of two patients who underwent enucleation for uveal melanoma and later developed regional lymph node metastases were reviewed. One of the two eyes was initially treated with proton beam irradiation. Histologic sections of the enucleated eyes and excised lymph nodes were examined. Results: The melanomas arose in the choroid and ciliary body of the two patients and spread to regional lymph nodes 2 years after enucleation. The choroidal melanoma recurred after irradiation, diffusely infiltrated the uveal tract, and extended into the conjunctiva via an emissary canal. The ciliary body melanoma spread through the trabecular meshwork to the conjunctiva. Conclusions: Choroidal and ciliary body melanoma may rarely exhibit regional lymph node metastasis. This mode of metastasis may occur after extraocular spread and invasion of conjunctival lymphatics.

Structured illumination microscopy of autofluorescent aggregations in human tissue.

Sections from human eye tissue were analyzed with Structured Illumination Microscopy (SIM) using a specially designed microscope setup. In this microscope the structured illumination was generated with a Twyman-Green Interferometer. This SIM technique allowed us to acquire light-optical images of autofluorophore distributions in the tissue with previously unmatched optical resolution. In this work the unique setup of the microscope made possible the application of SIM with three different excitation wavelengths (488, 568 and 647 nm), thus enabling us to gather spectral information about the autofluorescence signal.

Combination of structured illumination and single molecule localization microscopy in one setup

Understanding the positional and structural aspects of biological nanostructures simultaneously is as much a challenge as a desideratum. In recent years, highly accurate (20?nm) positional information of optically isolated targets down to the nanometer range has been obtained using single molecule localization microscopy (SMLM), while highly resolved (100?nm) spatial information has been achieved using structured illumination microscopy (SIM).In this paper, we present a high-resolution fluorescence microscope setup which combines the advantages of SMLM with SIM in order to provide high-precision localization and structural information in a single setup. Furthermore, the combination of the wide-field SIM image with the SMLM data allows us to identify artifacts produced during the visualization process of SMLM data, and potentially also during the reconstruction process of SIM images.We describe the SMLM?SIM combo and software, and apply the instrument in a first proof-of-principle to the same region of H3K293 cells to achieve SIM images with high structural resolution (in the 100?nm range) in overlay with the highly accurate position information of localized single fluorophores. Thus, with its robust control software, efficient switching between the SMLM and SIM mode, fully automated and user-friendly acquisition and evaluation software, the SMLM?SIM combo is superior over existing solutions.

Intravitreal Bevacizumab In Vascular Pigment Epithelium Detachment As A Result Of Subfoveal Occult Choroidal Neovascularization In Age-related Macular Degeneration

Purpose: The purpose of this study was to evaluate the effect of intravitreally administered bevacizumab on untreated vascularized pigment epithelium detachment (PED) in sub- or juxtafoveal occult choroidal neovascularization as a result of age-related macular degeneration. Methods: In this retrospective study, 28 untreated eyes of 26 patients (4 men, 22 women; mean age, 74.6 ± 7.2 years) with PED and sub- or juxtafoveal occult choroidal neovascularization as a result of age-related macular degeneration and additional intra- and/or subretinal fluid were treated with intravitreal injections of 1.25 mg bevacizumab. Baseline and follow-up visits included best-corrected visual acuity, complete ophthalmic examination, and Stratus optical coherence tomography. Fluorescein angiography was performed at baseline. Reinjections were performed if intra- and/or subretinal fluid persisted or recurred or PED increased. Results: Patients received 3.2 ± 1.8 injections (follow-up 37.9 ± 18.3 weeks). Mean maximum PED height showed a tendency to decrease (372 ± 150.5 μm to 290.3 ± 189 μm; P = 0.094). In 14 eyes (53.8%), PED height was reduced at last visit, including complete flattening in 1 eye. Mean visual acuity remained stable (0.58 ± 0.30 logarithm of the minimum angle of resolution to 0.58 ± 0.37 logarithm of the minimum angle of resolution; P = 0.905). Pigment epithelium detachment response to treatment did not correlate with baseline PED height or visual acuity at baseline or at the last visit. One patient sustained a retinal pigment epithelium rip, and another patient sustained an extensive subretinal hemorrhage. Conclusion: During bevacizumab therapy, mean PED height decreases in 50% of patients. No predictive factors for the response of PED to bevacizumab treatment could be identified. Treatment of PED with bevacizumab might result in a long-term functional benefit compared with the natural course.

Intravitreal bevacizumab for retinal capillary haemangioma: longterm results

Editor, V on Hippel)Lindau (VHL) disease is attended by multisystemic manifestations in many cases, but the central nervous system and retina are the most frequent locations of symptoms. Treatment of retinal capillary haemangioma caused by VHL disease can be a challenge and different approaches, such as laser photocoagulation, cryotherapy, photodynamic therapy, transpupillary thermotherapy and radiotherapy, have been tried with variable degrees of success (Garcia-Arumı́ et al. 2000). The VHL gene on chromosome 3, normally expressed in healthy people, is absent in VHL patients. This leads to an increase in the expression of vascular endothelial growth factor (VEGF) (Chan et al. 1999). Systemic anti-VEGF treatment has been reported in single cases, but this can be associated with severe side-effects (von Buelow et al. 2007). The longterm efficacy of intravitreal antiVEGF treatment has not yet been described for this disease. We report the outcome of intravitreal bevacizumab for retinal capillary haemangioma administered over a period of 2 years in a patient naı̈ve to this medication. A 40-year-old woman with VHL disease presented with a new retinal capillary haemangioma in the midperiphery in the left eye. Growth pattern was sessile with associated lipid exudation (Fig. 1A). Thirteen years earlier, a juxtapapillary haemangioma in the same eye had been treated with laser coagulation, resulting in scarred tissue and visual acuity (VA) of 20 ⁄ 400 (Fig. 1B). As a result of this experience, the patient refused further destructive procedures. After detailed discussion, intravitreal bevacizumab was offered as an off-label treatment option. The patient also suffered from several haemangiomas in the kidney, brain and right eye, the last of which had been treated with laser coagulation (VA 20 ⁄ 63). The patient did not receive any systemic treatment for VHL disease. When the patient had provided informed consent, a total of nine injections (administered every 13–14 weeks) of 2.5 mg bevacizumab were given intravitreally in the left eye over a period of 26 months. No adverse events attributable to intravitreal injections were observed and VA remained stable. The retinal capillary haemangioma did not grow significantly, whereas haemangiomas in other locations continued to grow and a new peripheral haemangioma appeared in the right, but not in the left, eye. The lipid exudation resolved almost completely and the feeder vessels did not enlarge (Fig. 1C). The new peripheral haemangioma in the fellow eye was treated with laser coagulation. Therapeutic strategies for retinal haemangiomas associated with VHL disease vary and often lead to unsatisfactory results, especially in centrally located haemangioma (Garcia-Arumı́ et al. 2000). Therefore, the increased intravitreal level of VEGF in VHL patients may represent a new target in effective therapy of retinal capillary haemangioma. In order to avoid an ongoing proliferation of retinal haemangioma caused by high VEGF expression, we administrated the VEGF antibody bevacizumab intravitreally. Injections were given every 13–14 weeks on the basis of our observations in patients with retinal vein occlusions. A dosage of 2.5 mg bevacizumab proved effective in the treatment of macular oedema for an average of 13 weeks. Over a period of > 2 years of treatment, the retinal haemangioma did not grow significantly and lipid exudation resolved completely. Dahr et al. (2007) presented similar results in their patients, but their observation time was only 1 year and this was marked by some adverse events. Here, no side-effects were reported, a finding in line with earlier reports on the safety of intravitreal bevacizumab (Fang et al. 2008). Anti-VEGF treatment reduces the permeability of retinal haemangiomas, which has also been observed after systemic administration of VEGF (A) (B)

Internal drainage in optic pit maculopathy

Optic disc pit with associated serous macular detachment has a poor visual prognosis if left to its natural course. It has been suspected that the subretinal fluid originates from the vitreous cavity via an inner retinoschisis-like separation within the papillomacular bundle between the optic disc pit and the central retinal detachment.1 We report a surgical approach on the basis of this assumed pathomechanism. A 20-year-old man presented with decreased vision in OD (right eye) due to macular detachment in association with an optic nerve pit (fig 1). Visual acuity was 20/400 OD and 20/20 OS (left eye). Optical coherence tomography revealed parapapillar retinoschisis-like separation of the outer retinal layers and …

Multifocal intraocular malignant melanoma: Report of two cases and review of the literature

PURPOSE To describe two eyes from two patients with multifocal primary intraocular melanoma. DESIGN Two case reports. METHODS The history and histologic findings in the enucleated eyes of two patients with multifocal intraocular melanoma are described in comparison to previously reported cases. MAIN OUTCOME MEASURES Pathologic examination of enucleated eyes. RESULTS One of the two eyes contained mixed cell type melanomas, and one eye contained spindle cell type melanomas. Examination of serial sections showed no continuity between the intraocular melanomas. There were no associated ocular or systemic conditions with the multifocal intraocular melanomas. CONCLUSIONS Multifocal primary intraocular melanoma is rare. There is no known predisposing factor to this condition.