Efficacy and Safety of Low-Intensity Pulsed Ultrasound-Induced Blood-Retinal Barrier Opening in Mice.

Systemic drugs can treat various retinal pathologies such as retinal cancers; however, their ocular diffusion may be limited by the blood-retina barrier (BRB). Sonication corresponds to the use of ultrasound (US) to increase the permeability of cell barriers including in the BRB. The objective was to study the efficacy and safety of sonication using microbubble-assisted low-intensity pulsed US in inducing a transient opening of the BRB. The eyes of C57/BL6J mice were sonicated at different acoustic pressures (0.10 to 0.50 MPa). Efficacy analyses consisted of fluorescein angiography (FA) performed at different timepoints and the size of the leaked molecules was assessed using FITC-marked dextrans. Tolerance was assessed by fundus photographs, optical coherence tomography, immunohistochemistry, RT-qPCR, and electroretinograms. Sonication at 0.15 MPa was the most suitable pressure for transient BRB permeabilization without altering the morphology or function of the retina. It did not increase the expression of inflammation or apoptosis markers in the retina, retinal pigment epithelium, or choroid. The dextran assay suggested that drugs up to 150 kDa in size can cross the BRB. Microbubble-assisted sonication at an optimized acoustic pressure of 0.15 MPa provides a non-invasive method to transiently open the BRB, increasing the retinal diffusion of systemic drugs without inducing any noticeable side-effect.

Long-term follow-up of retinal sensitivity assessed by microperimetry in patients with internal limiting membrane peeling.

PURPOSE: To evaluate anatomical and functional changes in patients with vitreomacular interface disease after internal limiting membrane (ILM) peeling, using microperimetry along with usual clinical and multimodal retinal imaging. METHODS: Patients with vitreomacular interface disease requiring vitrectomy underwent multimodal retinal evaluation, including visual acuity assessment, fundus color photograph, Spectral-Domain Optical Coherence Tomography, Optical Coherence Tomography-Angiography, and microperimetry. They were examined at baseline (M0), 6 months (M6) and 18 months (M18) after surgery. Retinal sensitivity was subdivided into three concentric polygons: Large, Medium, Small. RESULTS: Eleven eyes of 11 patients were analyzed, including 10 epiretinal membranes (ERMs). Best-corrected visual acuity (BCVA) improved in all patients from 0.51 logarithm of the minimal angle of resolution (logMAR) to 0.067 (p = 0.0074). Retinal sensitivity improved between M0 and M6 in all polygons and continued to improve between M6 and M18 for polygons Medium (M) and Small (S) with no statistical significance. At M18, BCVA and retinal sensitivity were similar in the operated eye compared with the fellow eye for all patients. Dissociated optic nerve fiber layer appearance was observed in 8 patients at M18. It was not correlated with either retinal sensitivity or BCVA or microscotomas. No recurrence of ERM or macular hole occurred during follow-up. CONCLUSION: After surgery, the retinal sensitivity assessed by microperimetry gradually improved until the 18th month and was not different from the values of the fellow eye. These results seemed to confirm that ILM peeling can be an effective and safe technique to treat patients with vitreomacular interface disease.

Prognostic factors of idiopathic epiretinal membrane surgery and evolution of alterations of the central cone bouquet.

PURPOSE: To describe the structural changes observed postoperatively in epiretinal membranes (ERM), in particular the alterations in the central cone bouquet (CB), and to identify prognostic factors that might predict postoperative outcome. METHODS: We included 125 eyes of 117 patients who underwent idiopathic ERM removal with at least a 6-month follow-up. For each patient, spectral-domain optical coherence tomography (SD-OCT) was performed and best-corrected visual acuity (BCVA) was measured, before and after surgery. RESULTS: Before surgery, 44 eyes (35.2%) presented CB alterations: 65.9% a cotton ball sign, 15.9% a foveolar detachment and 18.2% a pseudovitelliform lesion. Median BCVA increased from 20/63 to 20/32 post-operatively (p = .001) with a mean follow-up of 17 months. The disappearance of CB alterations after surgery was observed in 97.7% of eyes. In stage 3 and 4 ERM, ectopic inner foveal layers persisted in 76.7% of eyes after surgery. Postoperative BCVA was correlated with change in central macular thickness and initial BCVA and was not correlated with the presence of preoperative CB alteration, the initial stage of ERM, the presence of postoperative dissociated optical nerve fiber layer, and the disappearance of ectopic inner fiber layers. The combination of cataract surgery and capsulotomy did not seem to change visual outcome and seemed to accelerate visual recovery. Incidentally, general anesthesia was correlated with final BCVA. CONCLUSION: ERM surgery allowed a significant gain in BCVA and the disappearance of CB alterations in the great majority of cases. CB alteration did not show to be associated with poor visual prognosis.