Carsten Framme

Mobility experiments with microrobots for minimally invasive intraocular surgery.

PURPOSEnTo investigate microrobots as an assistive tool for minimally invasive intraocular surgery and to demonstrate mobility and controllability inside the living rabbit eye.nnnMETHODSnA system for wireless magnetic control of untethered microrobots was developed. Mobility and controllability of a microrobot are examined in different media, specifically vitreous, balanced salt solution (BSS), and silicone oil. This is demonstrated through ex vivo and in vivo animal experiments.nnnRESULTSnThe developed electromagnetic system enables precise control of magnetic microrobots over a workspace that covers the posterior eye segment. The system allows for rotation and translation of the microrobot in different media (vitreous, BSS, silicone oil) inside the eye.nnnCONCLUSIONSnIntravitreal introduction of untethered mobile microrobots can enable sutureless and precise ophthalmic procedures. Ex vivo and in vivo experiments demonstrate that microrobots can be manipulated inside the eye. Potential applications are targeted drug delivery for maculopathies such as AMD, intravenous deployment of anticoagulation agents for retinal vein occlusion (RVO), and mechanical applications, such as manipulation of epiretinal membrane peeling (ERM). The technology has the potential to reduce the invasiveness of ophthalmic surgery and assist in the treatment of a variety of ophthalmic diseases.

Correlation Between Hyperreflective Foci and Clinical Outcomes in Neovascular Age-Related Macular Degeneration After Switching to Aflibercept

PURPOSEnTo assess the correlation between hyperreflective foci (HF) and visual and anatomical outcomes in treatment-resistant neovascular age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT).nnnMETHODSnThis was a prospective interventional case series. Thirty-three eyes of 30 consecutive patients with treatment-resistant neovascular AMD were enrolled. Intravitreal aflibercept injections were performed at week 0 (baseline), week 4, and week 8. Spectral-domain OCT images were obtained before each injection and 4 weeks after the third injection. The main focus was on the measurement of choroidal neovascularization (CNV) size in the cross-sectional area in the B-scan through the fovea, and HF number along line segments of 1- and 3-mm length passing through the fovea.nnnRESULTSnMean number of HF in the radius of 500 μm decreased from 8.36 ± 7.58 to 4.15 ± 3.39 (P = 0.02). Mean number of HF in the radius of 1500 μm was reduced from 21.30 ± 12.47 to 10.45 ± 6.34 (P < 0.001). Mean CNV area decreased from 0.35 ± 0.22 to 0.22 ± 0.16 mm2 (P < 0.001). There was a significant positive correlation between HF reduction in the radius of 500 μm and decrease in central subfield thickness (CST) (r = 0.43, P = 0.01), but no statistically significant correlation was found between HF decline in the radius of 1500 μm and other parameters.nnnCONCLUSIONSnSwitching from ranibizumab to aflibercept caused significant decrease in the number of HF 1 month after aflibercept upload, and HF decrease in the radius of 500 μm was correlated positively with the reduction in CST.

Developing an in situ nanosuspension: A novel approach towards the efficient administration of poorly soluble drugs at the anterior eye

With about 50-60 million cases in the US alone, dry eye disease represents a severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a causal therapy. However, CsA is not sufficiently water soluble to be administrated via simple eye drops. We developed an in situ nanosuspension (INS) as a novel approach towards the administration of CsA to the cornea. It precipitates upon contact with the tear fluid and creates CsA nanoparticles that enter the cornea and release the drug by dissolution. We selected two liquid poly(ethylene glycols) (PEG) that dissolve CsA and create nanoparticles by precipitation of CsA upon water contact. Aqueous solutions of PEG and Solutol, a non-ionic surfactant, were well tolerated by primary human epithelial cells in vitro. To determine the critical water content needed for a precipitation, the solubility of CsA was investigated in quaternary systems of drug, solvent, surfactant and water. The best INS formulation showed a particle size of 505 ± 5 nm, a polydispersity index (PdI) of 0.23 ± 0.03 and a neutral zeta potential of -0.07 ± 0.05 mV. After single administration to porcine eyes in vitro, 3165 ± 597 ng(CsA)/g(cornea) were detected in corneal tissue, while the levels of Restasis a commercial formulation were, with 545 ± 137 ng(CsA)/g(cornea), significantly lower (P<0.01). These results demonstrate that an INS is a promising, novel approach towards the causal treatment of inflammatory diseases at the anterior eye.

Visual and anatomic outcomes after conversion to aflibercept in neovascular age-related macular degeneration: 12-month results.

Purpose To investigate 12-month outcomes of conversion to aflibercept in patients with neovascular age-related macular degeneration resistant to ranibizumab. Methods Twenty-two eyes of 19 consecutive patients received 3 monthly aflibercept injections followed by a pro re nata protocol. Spectral-domain optical coherence tomography (OCT) images were obtained before each injection. All 49 cross-sectional OCT B-scans obtained in each examination were investigated and the largest choroidal neovascularization (CNV) size was chosen. The same cross-sectional B-scan sections containing the maximum CNV size were used during the follow-up. Results After 12 months, best-corrected visual acuity increased from 45.68 ± 20.25 to 59.09 ± 17.50 Early Treatment Diabetic Retinopathy Study letters (p<0.001), central subfield thickness decreased from 399.91 ± 148.85 to 304.55 ± 97.89 μm (p = 0.003), area of CNV declined from 0.38 ± 0.24 to 0.28 ± 0.19 mm2 (p = 0.003), and macular volume improved from 9.64 ± 1.75 to 8.45 ± 0.98 mm3 (p<0.001). There was a significant resolution of intraretinal fluid (p = 0.016), but reduction of subretinal fluid was not significant (p = 0.25). Conclusions Visual and anatomic improvement were obtained after conversion to aflibercept.

Listeria monocytogenes endophthalmitis – case report and review of risk factors and treatment outcomes

BackgroundThe majority of cases of endophthalmitis are caused by exogenous pathogens; only 5–10xa0% are of endogenous origin. One cause of these rare cases of endogenous endophthalmitis is Listeria monocytogenes. Twenty-six cases of endophthalmitis due to this pathogen have been published over the last twenty years. The aim of this review is to summarize the main risk factors and common clinical findings of endogenous endophthalmitis due to Listeria monocytogenes.Case presentationWe report on a 62-year-old female presenting with a sterile hypopyon iritis with secondary glaucoma and an underlying rheumatoid disease. In microbiological analysis we identified Listeria monocytogenes. Further we searched through all published cases for typical signs, risk factors, details of medical and surgical treatment and outcome of endogenous endophthalmitis due to this rare pathogen.Ocular symptoms in almost all of these published cases included pain, redness of the eye, and decreased vision. Main clinical features included elevated intraocular pressure and fibrinous anterior chamber reaction, as well as a dark hypopyon. While the infection is typically spread endogenously, neither an exogenous nor endogenous source of infection could be identified in most cases. Immunocompromised patients are at higher risk of being infected than immunocompetent patients. The clinical course of endophthalmitis caused by Listeria monocytogenes had different visual outcomes. In some cases, the infection led to enucleation, blindness, or strong visual loss, whereas most patients showed a tendency of visual improvement during therapy.ConclusionEarly diagnosis and treatment initiation are crucial factors in the outcome of endogenous endophthalmitis caused by Listeria monocytogenes. This possible differential diagnosis should be kept in mind while treating patients with presumable sterile hypopyon and anterior uveitis having a high intraocular pressure. A bacterial source should be considered with a prompt initiation of systemic antibiotic treatment, mainly in immunocompromised patients, who develop endogenous anterior uveitis. An appropriate microbiological sampling is essential to detect atypical microorganisms and to choose an effective antibiotic treatment.

The short-term effects of aflibercept on the size of choroidal neovascularization lesion in treatment-resistant neovascular age-related macular degeneration as determined by spectral-domain optical coherence tomography

To evaluate the changes in the size of choroidal neovascularization (CNV) lesion using spectral domain‐optical coherence tomography (SD‐OCT) in patients with treatment‐resistant neovascular age‐related macular degeneration (AMD) who were switched from ranibizumab to aflibercept.

Ocular Blood Volume Index Based on Scattering Properties of Retinal Vessels Using Spectral Domain Optical Coherence Tomography

ABSTRACT Introduction: The evaluation of retinal vessels and the retinal blood flow is important for ocular diseases. We introduce a spectral domain optical coherence tomography (SD-OCT) based method for facilitating a retinal blood vessel analysis using the scattering properties of retinal vessels. The intensity of the distal shadow of vessels caused by the scattered signal is measured, correlated with the pulsatile ocular blood flow (POBF), and its repeatability is analyzed. Methods: About 20 eyes of 20 healthy, young participants (mean age 23.15 years, standard deviation 2.3 years) were included in the analysis. Participants underwent ophthalmic diagnostics including three repeated SD-OCT examinations and measurement of POBF. The vessel shadow intensity analysis is based on peripapillary SD-OCT scans and automatically analyses the intensity of the distal vessel shadow compared to its surroundings. Results: The distal shadow of arteries in SD-OCT scans correlated with the POBF (r = 0.647, p = 0.002). Furthermore, the shadow intensity correlated with the established morphological arterio-venous ratio. The evaluation of repeatability was performed using the interclass correlation coefficient (ICC), showing good repeatability for individual vessels (ICC = 0.825) and arteries (ICC = 0.820). Conclusions: In summary, we indicate that the scattering properties of retinal vessels in SD-OCT images might correlate with the vessel morphology and for retinal arteries with the retinal blood flow volume as well. Further studies are needed to establish this method’s sensitivity and specificity in participants with retinal and cardiovascular diseases.

Optical coherence tomography angiography analysis of macular flow density in glaucoma

Modifications in ocular blood flow may play a significant role in glaucoma development. Optical coherence tomography angiography (OCT‐A) is based on the detection and analysis of the reflection behaviour of motion in a static environment and therefore is able to quantify the retinal flow density. We used this new technology to examine the density of the active flow vasculature in the macular area in glaucoma patients compared to healthy patients.

Author's Reply to Comments to: Visual and Anatomic Outcomes after Conversion to Aflibercept in Neovascular Age-Related Macular Degeneration: 12-Month Results

effects due to the presumed pharmacologic advantages of aflibercept but to explore if there is a beneficial effect for the patients with this new drug at that time. We could show that visual and anatomic improvement was obtained after conversion to aflibercept in at least 1/3 of the patients in whom ranibizumab therapy was unsuccessful. 5. As we mentioned in our introduction, the resistance from prolonged use of ranibizumab might have been caused by development of tachyphylaxis and/or tolerance, which is not exclusively seen in our series. On the other hand, it is not clear if the proposed fixed dosing regimen after the loading phase would have been better. Various studies show that the outcome of well-conducted pro re nata injections is comparable to a fixed monthly dose, which is (just morphologically) better than the fixed bimonthly treatment. Therefore, that is another unproven hypothesis.