Electrostatic complex of neurotrophin 4 with dendrimer nanoparticles: controlled release of protein in vitro and in vivo.

Background: NT4 has been regarded as a promising therapeutic protein for treatment of damaged retinal pigment epithelium cells. Purpose: Here, we studied physicochemical parameters of an NT4-polyamidoamine (PAMAM) electrostatic complex, which can provide a sustained concentration of protein in intraocular space over an extended period after delivery. Adsorption/desorption of NT4 molecules to/from positively charged PAMAM dendrimers were precisely determined to control the concentration of bounded/unbounded protein molecules, diffusion coefficient, and size of a protein-laden dendrimer structure. We determined kinetics of NT4 desorption in PBS, vitreous, and damaged retina. Methods: Initially, adsorption of NT4 molecules on PAMAM dendrimers was studied in PBS using dynamic light scattering, electrophoresis, solution depletion, ELISA, and atomic force microscopy. This allowed us precisely to determine desorption of NT4 from nanoparticles under in situ conditions. The maximum coverage of irreversibly adsorbed NT4 determined by ELISA allowed us to devise a robust procedure for preparing stable and well-controlled coverage of NT4 on PAMAM nanoparticles. Thereafter, we studied diffusion of nanospheres containing NT4 molecules by injecting them into vitreous cavities of mice exposed to intravenous injections of sodium iodate and evaluated their intraocular desorption kinetics from drug carriers in vivo. Results: Our measurements revealed NT4-dendrimer nanoparticles can be used for continuous neurotrophic factor delivery, enhancing its distribution into mouse vitreous, as well as damaged retina over 28 days of postinjury observation. Conclusion: Understanding of polyvalent neurotrophin interactions with dendrimer nanoparticles might be useful to obtain well-ordered protein layers, targeting future development of drug-delivery systems, especially for neuroprotection of damaged retinal neurons.

Sub-hyaloid and sub-internal limiting membrane macular hemorrhage after laser exposure at music festival: a case report.

PURPOSE: To describe the first case of a combined sub-hyaloid and sub-internal limiting membrane macular hemorrhage after recreational laser exposure. METHODS: A 23-year-old patient presented with an acute loss of vision in his right eye (OD) immediately after a brief exposure to a laser beam at a music festival. Color photography, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinogram (mfERG) were performed for diagnosis and follow-up. RESULTS: On presentation, visual acuity was 20/400 in the OD and 20/20 in the left eye. Posterior segment examination of his OD revealed a preretinal hemorrhage at the macula. SD-OCT images exposed a combined sub-hyaloid and sub-internal limiting membrane localization. Successful VPP with ILM peeling was carried out. Although sequential mfERG displayed almost complete restoration of the P1 amplitude 6 months posterior to VPP, SD-OCT demonstrated permanent damage to outer retinal layers. Final BCVA on OD was 20/30. CONCLUSION: The expanding and unregulated use of lasers in everyday life has created an increasing amount of cases of laser-induced retinopathy in recent years. Much more attention should be addressed in laser safety and awareness to prevent future ocular injuries. In acute phases of sub-hyaloid hemorrhages blocking direct visualization of the posterior pole, mfERG is a valuable tool to address initial macular pathology.

Large Traumatic Retinal Dialysis Associated With Prominent Vitreous Base Avulsion.

A 13-year-old female with a history of regressed retinopathy of prematurity presented with new-onset floaters after sustaining blunt force trauma to her left eye. Best-corrected visual acuity was 20/20 in both eyes (OU), with an intraocular pressure of 14 mm Hg and 15 mm Hg in the right eye (OD) and left eye (OS), respectively. Exam under anesthesia revealed an unremarkable anterior segment OU, including no hyphema or subluxated crystalline lens. Scleral depression OS demonstrated a retinal dialysis superotemporally (1-o'clock to 3-o'clock) and nasally (7-o'clock to 10-o'clock) associated with a prominent vitreous base avulsion but no subretinal fluid (Figure). Scleral depression OD was unremarkable. Both areas of retinal dialysis OS were treated with three rows of indirect green laser photocoagulation posterior to the edge of the dialysis. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:731.].

EX VIVO MODEL FOR THE CHARACTERIZATION AND IDENTIFICATION OF DRYWALL INTRAOCULAR FOREIGN BODIES ON COMPUTED TOMOGRAPHY.

BACKGROUND: The study was inspired after the authors encountered a patient with a penetrating globe injury due to drywall, who had retained intraocular drywall foreign body. Computed tomography (CT) was read as normal in this patient. Open globe injury with drywall has never been reported previously in the literature and there are no previous studies describing its radiographic features. METHODS: The case report is described in detail elsewhere. This was an experimental study. An ex vivo model of 15 porcine eyes with 1 mm to 5 mm fragments of implanted drywall, 2 vitreous only samples with drywall and 3 control eyes were used. Eyes and vitreous samples were CT scanned on Days 0, 1, and 3 postimplantation. Computed ocular images were analyzed by masked observers. Size and radiodensity of intraocular drywall were measured using Hounsfield units (HUs) over time. RESULTS: Intraocular drywall was hyperdense on CT. All sizes studied were detectable on Day 0 of scanning. Mean intraocular drywall foreign body density was 171 ± 52 Hounsfield units (70-237) depending on fragment size. Intraocular drywall foreign body decreased in size whereas Hounsfield unit intensity increased over time. CONCLUSION: Drywall dissolves in the eye and becomes denser over time as air in the drywall is replaced by fluid. This study identified Hounsfield Units specific to intraocular drywall foreign body over time.

TRAUMATIC PROLIFERATIVE VITREORETINOPATHY: Clinical and Histopathological Observations.

PURPOSE: To determine the phases of traumatic proliferative vitreoretinopathy after open globe injury by assessing cellular components, extracellular matrix constituents of proliferative vitreoretinopathy membranes, and intraretinal changes over time. METHODS: Twenty-one epiretinal and/or subretinal membrane specimens were obtained from 21 patients with open globe injuries. The patients were divided into Groups A (≤28 days), B (29-120 days), and C (>120 days) according to the interval between injury and vitrectomy. The staining intensity and percentage of positive cells in membranes were compared among the groups, and proliferative indices for Ki-67 and proliferating cell nuclear antigen were assessed. Intraretinal changes were evaluated through histology and immunohistochemistry. Fundus photography was performed during vitrectomy. RESULTS: The proliferating cell nuclear antigen proliferative index was significantly higher in Group B (P = 0.002) than in Group A, and lower in Group C (P < 0.001) than in Group B. α-smooth muscle actin expression increased from day 29 to 120 after injury. Meanwhile, intraretinal gliosis and fibrosis developed. CONCLUSION: Active proliferation and contraction in proliferative vitreoretinopathy membranes continue until 120 days after injury, and are accompanied by the initiation of intraretinal gliosis and fibrosis. These findings provide further insight into the optimal timing of vitrectomy after trauma.

Computing the stresses and deformations of the human eye components due to a high explosive detonation using fluid-structure interaction model.

INTRODUCTION: In spite the fact that a very small human body surface area is comprised by the eye, its wounds due to detonation have recently been dramatically amplified. Although many efforts have been devoted to measure injury of the globe, there is still a lack of knowledge on the injury mechanism due to Primary Blast Wave (PBW). The goal of this study was to determine the stresses and deformations of the human eye components, including the cornea, aqueous, iris, ciliary body, lens, vitreous, retina, sclera, optic nerve, and muscles, attributed to PBW induced by trinitrotoluene (TNT) explosion via a Lagrangian-Eulerian computational coupling model. MATERIALS AND METHODS: Magnetic Resonance Imaging (MRI) was employed to establish a Finite Element (FE) model of the human eye according to a normal human eye. The solid components of the eye were modelled as Lagrangian mesh, while an explosive TNT, air domain, and aqueous were modelled using Arbitrary Lagrangian-Eulerian (ALE) mesh. Nonlinear dynamic FE simulations were accomplished using the explicit FE code, namely LS-DYNA. In order to simulate the blast wave generation, propagation, and interaction with the eye, the ALE formulation with Jones-Wilkins-Lee (JWL) equation defining the explosive material were employed. RESULTS: The results revealed a peak stress of 135.70kPa brought about by detonation upsurge on the cornea at the distance of 25cm. The highest von Mises stresses were observed on the sclera (267.3kPa), whereas the lowest one was seen on the vitreous body (0.002kPa). The results also showed a relatively high resultant displacement for the macula as well as a high variation for the radius of curvature for the cornea and lens, which can result in both macular holes, optic nerve damage and, consequently, vision loss. CONCLUSION: These results may have implications not only for understanding the value of stresses and strains in the human eye components but also giving an outlook about the process of PBW triggers damage to the eye.

Intraocular foreign bodies extracted by pars plana vitrectomy: clinical characteristics, management, outcomes and prognostic factors.

BACKGROUND: Intraocular foreign bodies (IOFBs) are an important cause of visual loss within the group of working age population. We aim to present the clinical features and the algorithm according to which we manage the foreign bodies that are located in the posterior segment of the eye. We define the outcomes and the prognostic factors that influenced the final visual acuity and globe survival in patients with IOFBs that we extracted by pars plana vitrectomy (PPV) over a 5-year period. METHODS: We reviewed the medical records of all the cases with IOFBs that we removed by PPV, over 5 years (2009-2013). We extracted the following parameters: age, gender, wound anatomy, IOFB characteristics, ocular lesions, initial and final visual acuities. We used the program SPSS version 20.0.0. for the statistical analysis of our data. RESULTS: During 5 years, we treated 21 IOFBs by PPV, representing 12.20 % of all the open globe injuries. All the patients were males with the median age of 36 years. The foreign body was located in the vitreous - 11 cases (52.38 %), retina--seven cases (33.33 %) and perforating--three cases (14.28 %). Retinal detachment (RD) at presentation was identified in eight cases (38.09 %) and endophthalmitis, in six cases (28.57 %). The visual outcome was significantly worse in patients with RD at presentation (p = 0.012) and with IOFBs larger than 3 mm (p = 0.042). Endophthalmitis did not influence the visual outcome. CONCLUSIONS: The worse prognostic factors were: RD at presentation and large foreign body. TRIAL REGISTRATION NUMBER: IRCT2015040418966N3 / Apr. 9/2015.

Intravitreal cilium associated with retinal detachment 40 years following penetrating eye injury: a case report.

BACKGROUND: The presence of an intraocular cilium is very rare and the response of the eye to the cilium is variable. We present the case of a patient with a cilium found in the vitreous cavity during vitrectomy for rhegmatogenous retinal detachment 40 years following penetrating eye injury. To our knowledge, this is the longest reported presence of a cilium in the vitreous cavity. CASE PRESENTATION: A 70-year-old Caucasian woman presented to the emergency department of our hospital complaining of sudden visual impairment and floaters of her right eye initiated 2 weeks earlier. Ophthalmic history included a penetrating injury of the right eye with a sharp metallic object 40 years ago and an uncomplicated phacoemulsification surgery in the same eye 2 years earlier. Fundoscopy revealed an inferior macula off rhegmatogenous retinal detachment. No inflammation was present. During vitrectomy and under scleral indentation at 5-o'clock position, a cilium was found at far retinal periphery. One end of the cilium was embedded in the retina, whereas the other end floated freely in the vitreous. The cilium was removed through the pars plana sclerotomy with intraocular foreign body forceps. The procedure was completed without any complications. CONCLUSION: Penetrating eye injury is the most possible cause of cilium entrance in vitreous cavity in this case, which suggests that cilium can be well tolerated in vitreous cavity for as long as 40 years.

Experimental analyses of the retinal and subretinal haemorrhages accompanied by shaken baby syndrome/abusive head trauma using a dummy doll.

INTRODUCTION: We explored several modes of violent shaking using a dummy doll with an eyeball model to reproduce abusive events that lead to retinal haemorrhages (RH) seen in shaken baby syndrome or abusive head trauma (SBS/AHT). MATERIALS AND METHODS: A dummy doll equipped with an eyeball model was prepared. The eyeball model was filled with a model of vitreous body, i.e. agar gel or water, and was with a pressure sensor to measure normal stress. RESULTS: The modes of shaking were classified into three patterns, i.e. fast shaking with the fore arms, fast shaking with the whole arms and synchronized shaking with the whole arms. The frequency of the cyclic acceleration-deceleration history experienced by the head of the dummy doll was 5.0, 4.0 and 2.2 Hz, respectively, with the maximum acceleration of 20, 20 and 60 m/s(2), respectively. We considered the last of these three modes of shaking as possibly corresponding to the worst case of violent shaking. This mode of shaking could be instructed to volunteers who acted as imitate perpetrators, and resulted in both increased peak intensities of the acceleration experienced by the head of the dummy doll and increased stresses on the retina at the posterior pole of the eyeball model. DISCUSSION: The time integral of the stress through a single cycle of shaking was 107 Pa·s, much larger than that of a single event of fall, which resulted in 60-73 Pa·s. Taking into account that abusive shaking is likely to include multiple cycles, the time integral of the stress due to abusive shaking can be even larger. This clear difference may explain why RH in SBS/AHT is frequent, while RH in accidental falls is rare.

23-gauge vitrectomy with intraocular foreign body removal via the limbus: an alternative approach for select cases.

PURPOSE: To study the outcome of removal of retained intraocular foreign bodies (RIOFBs) via limbus using 23-gauge transconjunctival sutureless vitrectomy (TSV). MATERIALS AND METHODS: In this prospective, non-comparative interventional case series, fourteen eyes of 14 patients fulfilling the inclusion criteria were enrolled. They underwent 23-gauge TSV for management of posterior segment RIOFB and reviewed at 1 day, 7 days, 6 weeks, 3, 6 and 12 months. Eyes with penetrating eye injury involving cornea or limbus (corneal injury not so severe to hinder vitrectomy), cataract associated with anterior and/or posterior capsular tear requiring cataract surgery and posterior segment RIOFB with minimal posterior segment involvement were included. Main outcome measures include success in removal of RIOFB without enlarging sclerotomy, ability to preserve capsular support, improvement in visual acuity and complications, if any. RESULTS: All eyes underwent the successful RIOFB removal through limbal port without enlarging scleral ports. None of the eyes required suturing of the sclera, cornea or conjunctiva. Anterior capsular rim could be preserved in all eyes except one. Postoperatively follow up ranged from one year in 8, 6 months in 4 and 3 months in 2 eyes. The mean logMAR visual acuity at 3, 6, and 12 months showed significant improvement. There were no intraoperative complications. Postoperative complications include microscopic hyphema and loose blood in vitreous cavity in one eye. CONCLUSION: The advantages of 23-gauge TSV for removal of RIOFB may be passed on to select cases. RIOFB removal through limbal route obviated the need for scleral port enlargement and preserved capsular support for early visual rehabilitation.

[Treatment for penetrating wound caused by metallic intraocular foreign body]. / REZOLVAREA UNEI PLAGI PENETRANTE CU CORP STRAIN INTRAOCULAR METALIC.

INTRODUCTION: Penetrating wounds with intraocular foreign body are ophthalmologic emergencies due to their severity and complexity and may require multiple surgeries for final resolution. CASE REPORT: 30-years-old patient with penetrating wound and metallic intraocular foreign body in the posterior vitreous requires successive operations for IOFB extraction, lensectomy, posterior vitrectomy for rhegmatogenous retinal detachment and then silicone oil extraction with final visual acuity 0, 4 PH.