Impact of Silicone Oil Removal on Macular Perfusion.

(1) Background: Silicone oil (SO) can be used as an endotamponade during vitreoretinal surgery for retinal detachment. There is emerging evidence that SO filling of the vitreous cavity and its removal may impact macular perfusion. So far, studies have not focused on choroidal sublayer perfusion, yet. (2) Methods: Optical coherence tomography angiography was applied in 19 patients with SO endotamponade before and four weeks after removal of SO. (3) Results: Perfusion of choriocapillaris increased significantly after SO removal, while perfusion of Haller's and Sattler's layer decreased significantly. (4) Conclusions: Removal of SO impacts choroidal perfusion and leads to a perfusion shift within choroidal sublayers. This study underlines that it is worth to conduct larger prospective studies that evaluate the choroidal perfusion and its functional implications in more detail.

Pralsetinib in RET fusion-positive non-small-cell lung cancer: A real-world data (RWD) analysis from the Italian expanded access program (EAP).

OBJECTIVES: The selective RET-inhibitor pralsetinib has shown therapeutic activity in early clinical trials in patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) gene fusions. To date, the real-world efficacy of pralsetinib in this population is unknown. MATERIALS AND METHODS: A retrospective efficacy and safety analysis was performed on data from patients with RET-fusion positive NSCLC enrolled in the pralsetinib Italian expanded access program between July 2019 and October 2021. RESULTS: Overall, 62 patients with RET-fusion positive NSCLC received pralsetinib at 20 Italian centers. Next-generation sequencing was used to detect RET alterations in 44 patients (73 %). The most frequent gene fusion partner was KIF5B (75 % of 45 evaluable). Median age was 62 years (range, 36-90), most patients were female (57 %) and never smokers (53 %). Brain metastases were known in 18 patients (29.5 %) at the time of pralsetinib treatment. 13 patients were treatment naïve (unfit for chemotherapy), 48 were pretreated (median number of previous lines: 1, range, 1-4). The objective response rate (ORR) was 66 % [95 % confidence interval (CI), 53-81] in the evaluable population (n = 59). The disease control rate (DCR) was 79 %. After a median follow-up of 10.1 months, the median progression free survival was 8.9 months (95 %CI, 4.7-NA). In patients with measurable brain metastases (n = 6) intracranial ORR was 83 %, intracranial DCR was 100 %. Overall, 83.6 % of patients experienced any-grade treatment-related adverse events (TRAEs), 39 % grade 3 or greater (G ≥ 3). The most common G ≥ 3 TRAEs were neutropenia (9.8 %), dry mouth/oral mucositis (8.2 %), and thrombocytopenia (6.6 %). Seven patients (12 %) discontinued pralsetinib due to TRAEs, twenty-six had at least one dose level modification due to TRAEs. Two treatment-related deaths were observed (1 sepsis, 1 typhlitis). CONCLUSIONS: In the real-world setting, pralsetinib confirmed durable systemic activity and intracranial response in RET-fusion positive NSCLC. Toxicity profile was consistent with previous reports.

Sutureless amniotic membrane fixation using fibrin glue for ocular surface reconstruction in a rabbit model.

PURPOSE: Amniotic membrane transplantation has become an important treatment option for corneal surface reconstruction. However, suture fixation of the transplant has various disadvantages like corneal irritation, scarring, graft loss due to membrane shrinkage, and the need for subsequent suture removal. Replacement of sutures by bioadhesives might be an advantageous alternative. This controlled study was designed to evaluate a new sutureless technique for amniotic membrane fixation onto the corneal surface by using fibrin glue. METHODS: Standardized disks of cryopreserved amniotic membranes were transplanted onto the deepithelialized cornea of 12 rabbits using either conventional suture fixation or a new fibrin glue technique. The rabbits were followed-up with slit-lamp examination and fluorescein staining until epithelialization was completed. Consecutively, the rabbits were killed and the eyes processed for histology and immunohistochemistry for cytokeratin-3. RESULTS: All membranes of both groups stayed in place throughout the follow-up time and showed a progressive graft epithelialization that was completed after 12 days. Whereas suture-fixated membranes showed progressive tissue shrinkage, fibrin-glued sheets remained unaltered. In the bioadhesive group, histology revealed a smooth fibrin layer in the graft-host interface and a continuous, stratified layer of cytokeratin-3 expressing corneal epithelial cells on the membrane surface. In contrast, suture-fixated membranes showed contracted and prominent membrane edges with epithelial ingrowth into the submembrane interface. CONCLUSION: Our results demonstrate the general feasibility of reproducible and reliable sutureless amniotic membrane fixation onto the corneal surface in rabbits. Stable adherence is maintained until epithelialization is completed. The sutureless technique gives sufficient manipulation time for the sheet before the final cross-linking process is completed. Furthermore, several advantageous characteristics could be demonstrated as increased biocompatibility, better epithelialization pattern and the lack of membrane shrinkage.

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement.

Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis, hypo-salivation and xerostomia, trismus, radiation caries etc.), are often debilitating. These effects tend to be underestimated and insufficiently addressed in the medical community. A multidisciplinary group of head and neck cancer specialists met in Milan with the aim of reaching a consensus on clinical definitions and management of these toxicities. The Delphi Appropriateness method was used for developing the consensus, and external experts evaluated the conclusions. This paper contains 10 clusters of statements about the clinical definitions and management of head and neck cancer treatment sequels (dental pathologies and osteo-radionecroses) that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecroses (10 clusters of statements), whereas this second part deals with trismus and xerostomia.

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement.

Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements).

Experimental implantation and long-term testing of an intraocular vision aid in rabbits.

OBJECTIVE: To develop an intraocular vision aid to provide artificial vision in severely traumatized eyes, where neuroretinal function could be preserved but irreversible anterior segment opacification resulted in blindness. METHODS: The basis of an intraocular vision aid is in principle a telemetric circuit to bridge the opaque cornea and to allow for artificial light stimulation of the retina. The visual prosthesis comprises an external high-dynamic range complementary metal oxide semiconductor camera and digital signal processing unit and an intraocular miniaturized light-emitting diode array to project the image onto the retina. For in vivo testing of long-term function and biocompatibility, silicone-encapsulated active photodiodes were implanted in 13 pigmented rabbits and were followed up for up to 21 months. RESULTS: Lens extraction and stable fixation of the device in the ciliary sulcus were successful in all cases. For up to 21 months inductive energy transmission and wireless stimulation of the implants could be maintained. Electrophysiologic data and histology demonstrated a good tissue biocompatibility in the long-term follow-up. CONCLUSION: The results demonstrate the general feasibility and biocompatibility to implant and fixate an intraocular light-emitting diode prosthesis. Inductive energy transmission to the intraocular device and wireless light stimulation are assured in the long term but depend on meticulous water-impermeable encapsulation of the delicate microelectronic components. Clinical Relevance An intraocular vision aid compound system with a high-resolution light-emitting diode matrix might be a future treatment option to restore vision in blind eyes with severe anterior segment disorders.

Primary silicone oil tamponade in the management of severe intraocular foreign body injuries: an 8-year follow-up.

PURPOSE: To evaluate the long-term outcome of pars plana vitrectomy and primary silicone oil tamponade in patients with severe intraocular foreign body (IOFB) injuries and high risk of proliferative vitreoretinopathy (PVR). METHODS: This retrospective consecutive study included 23 patients with severe IOFB injuries who had extensive lacerations including sclera, choroid, and retina, and were complicated by predictive factors for elevated proliferative activity and an unfavorable outcome. All patients underwent pars plana vitrectomy, removal of the IOFB, and primary silicone oil tamponade and were followed up for a mean 8.9 years. Main functional outcome was assessed as final best-corrected visual acuity. Anatomic success was defined as permanent retinal attachment. RESULTS: PVR occurred in 70% of all eyes and required 16 revisions. Silicone oil was removed in 78% of the eyes after a mean tamponade duration of 9.1 months. Complete retinal attachment was achieved in 83% of the eyes. Three eyes developed a persisting hypotony that was stabilized under permanent silicone oil. Functional stabilization was observed in the third year resulting in a final visual acuity of 20/630. Useful vision of better than 20/400 could be preserved in 55% of the patients. Only one eye underwent a late enucleation after 6.8 years. CONCLUSIONS: Primary silicone oil stabilizes the retina during the critical period of active PVR and may limit the visual loss in selected high-risk eyes in the long term.