Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma.

Intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury (ONI) or laser-induced ocular hypertension (OHT). In models of glaucoma, BDNF therapy can delay or halt RGCs loss, but this protection is time-limited. The decreased efficacy of BDNF supplementation has been in part attributed to BDNF TrkB receptor downregulation. However, whether BDNF overexpression causes TrkB downregulation, impairing long-term BDNF signaling in the retina, has not been conclusively proven. After ONI or OHT, when increased retinal BDNF was detected, a concomitant increase, no change or a decrease in TrkB was reported. We examined quantitatively the retinal concentrations of the TrkB protein in relation to BDNF, in a course of adeno-associated viral vector gene therapy (AAV2-BDNF), using a microbead trabecular occlusion model of glaucoma. We show that unilateral glaucoma, with intraocular pressure ( IOP) increased for five weeks, leads to a bilateral decrease of BDNF in the retina at six weeks, accompanied by up to four-fold TrkB upregulation, while a moderate BDNF overexpression in a glaucomatous eye triggers changes that restore normal TrkB concentrations, driving signaling towards long-term RGCs neuroprotection. We conclude that for glaucoma therapy, the careful selection of the appropriate BDNF concentration is the main factor securing the long-term responsiveness of RGCs and the maintenance of normal TrkB levels.

A retrospective analysis of the intraocular lens power calculation in cases of sulcus fixation.

PURPOSE: To evaluate the refractive results in patients with intraocular lenses fixated in the sulcus of posterior chamber. Sulcus fixation causes a more anterior position of IOL than had been intended during the preoperative power calculation. A lack of correction of the IOL's power results in a myopic shift. MATERIAL AND METHODS: 27 patients (27 eyes) who underwent cataract surgery by phacoemulsification and foldable IOL MA60BM sulcus fixation due to a posterior capsule rupture at the Department of Ophthalmology, Medical University of Warsaw. The position of the IOL was confirmed by ultrabiomicroscopy. The study included patients with axial lengths ranging from 22 to 25 mm. Patients who suffered from a corneal astigmatism of > 1,00 Dcyl prior to the surgery were excluded from the study. The study also excluded patients with vitreous loss as this causes the anterior chamber to become deeper after vitrectomy, and consequently the IOL might sit in a more posterior position. The difference between the predicted and the postoperative refraction was evaluated. RESULTS: The mean visual acuity was significantly better after cataract surgery. The best corrected visual acuity (BCVA) was 1.0, which occurred in 19 cases (70%). The myopic shift, which was assessed as a mean difference between the predicted and the postoperative refraction after sulcus fixation, was 1.25 D. CONCLUSIONS: In order to avoid a myopic shift in the case of sulcus fixation, the IOL power calculation should be adjusted accordingly. The authors recommend that the IOL power should be reduced by approximately 1.25 to 1.50 D in emetropic eyes.

Specvis: Free and open-source software for visual field examination.

Visual field impairment affects more than 100 million people globally. However, due to the lack of the access to appropriate ophthalmic healthcare in undeveloped regions as a result of associated costs and expertise this number may be an underestimate. Improved access to affordable diagnostic software designed for visual field examination could slow the progression of diseases, such as glaucoma, allowing for early diagnosis and intervention. We have developed Specvis, a free and open-source application written in Java programming language that can run on any personal computer to meet this requirement (http://www.specvis.pl/). Specvis was tested on glaucomatous, retinitis pigmentosa and stroke patients and the results were compared to results using the Medmont M700 Automated Static Perimeter. The application was also tested for inter-test intrapersonal variability. The results from both validation studies indicated low inter-test intrapersonal variability, and suitable reliability for a fast and simple assessment of visual field impairment. Specvis easily identifies visual field areas of zero sensitivity and allows for evaluation of its levels throughout the visual field. Thus, Specvis is a new, reliable application that can be successfully used for visual field examination and can fill the gap between confrontation and perimetry tests. The main advantages of Specvis over existing methods are its availability (free), affordability (runs on any personal computer), and reliability (comparable to high-cost solutions).

Glaucoma -state of the art and perspectives on treatment.

Glaucoma is a chronic optic neuropathy characterized by progressive damage to the optic nerve, death of retinal ganglion cells and ultimately visual field loss. It is one of the leading causes of irreversible loss of vision worldwide. The most important trigger of glaucomatous damage is elevated eye pressure, and the current standard approach in glaucoma therapy is reduction of intraocular pressure (IOP). However, despite the use of effective medications or surgical treatment leading to lowering of IOP, progression of glaucomatous changes and loss of vision among patients with glaucoma is common. Therefore, it is critical to prevent vision loss through additional treatment. To implement such treatment(s), it is imperative to identify pathophysiological changes in glaucoma and develop therapeutic methods taking into account neuroprotection. Currently, there is no method of neuroprotection with long-term proven effectiveness in the treatment of glaucoma. Among the most promising molecules shown to protect the retina and optic nerve are neurotrophic factors. Thus, the current focus is on the development of safe and non-invasive methods for the long-term elevation of the intraocular level of neurotrophins through advanced gene therapy and topical eye treatment and on the search for selective agonists of neurotrophin receptors affording more efficient neuroprotection.