Walid Abdallah

Anti-VEGF therapy in proliferative diabetic retinopathy

Diabetic retinopathy remains one of the leading causes of blindness in 20-year-old to 64-year-old individuals in the industrialized working population, despite the significant advances in ophthalmology. Retinal neovascularization, a hallmark of proliferative diabetic retinopathy (PDR), is considered an important risk factor for severe vision loss in patients with diabetes mellitus (DM). The diabetic retinopathy study showed that scatter laser panretinal photocoagulation (PRP) reduces severe vision loss by 50% for patients who have high risk characteristics. According to the Early Treatment Diabetic Retinopathy study (ETDRS), PRP may be associated with adverse changes on the visual field. Furthermore, approximately 4.5% of patients with PDR in the ETDRS required pars plana vitrectomy despite panretinal laser photocoagulation. Surgery may be challenging and complicated, especially when dealing with patients suffering from severe complications of PDR. Much of the morbidity associated with PDR reflects the deleterious effects of long standing DM on the retinal microcirculation. During the past few decades, our understanding of the cellular and subcellular mechanisms of this microcirculatory injury led to the discovery of vascular endothelial growth factor (VEGF) that was first recognized as a vasopermeability factor. The growth of new vessels in response to retinal ischemia (factor X) was initially proposed by Michaelson more than half a century ago. VEGF was recently demonstrated to be the main mediator of ocular neovascularization. This finding was further confirmed as VEGF levels were directly correlated with severity of PDR whereas reduction in VEGF levels was demonstrated after successful laser treatment of PDR.

Vitreal oxygenation in retinal ischemia reperfusion.

PURPOSE To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. METHODS Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (Po(2)) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal Po(2) in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized. RESULTS Mean final (d12) Po(2) was 10.64 ± 0.77 mm Hg for the oxygenation group, 2.14 ± 0.61 mm Hg for the sham group, and 1.98 ± 0.63 mm Hg for the no treatment group. On ERG, scotopic b-wave amplitude was significantly preserved in the oxygenation group compared with the other two groups. Superoxide dismutase assay showed higher activity in the operated eyes than in the nonoperated control eyes in the sham treatment group and no treatment group only. Histopathology showed preservation of retinal architecture and choroidal vasculature in the oxygenation group, whereas the sham-treated and nontreated groups showed retinal thinning and choroidal atrophy. CONCLUSIONS In severe total ocular ischemia, anterior vitreal oxygenation supplies enough oxygen to penetrate the retinal thickness, resulting in rescue of the RPE/choriocapillaris that continues to perfuse, hence sparing the retinal tissue from damage.

Evaluation of Ultrasound-Assisted Thrombolysis Using Custom Liposomes in a Model of Retinal Vein Occlusion

PURPOSE To study the potential efficacy of ultrasound (US) assisted by custom liposome (CLP) destruction as an innovative thrombolytic tool for the treatment of retinal vein occlusion (RVO). METHODS Experimental RVO was induced in the right eyes of 40 rabbits using laser photothrombosis; the US experiment took place 48 hours later. Rabbits were randomly divided into four equal groups: US+CLP group, US+saline group, CLP+sham US group, and no treatment group. The latter three groups acted as controls. Fundus fluorescein angiography and Doppler US were used to evaluate retinal blood flow. RESULTS CLP-assisted US thrombolysis resulted in restoration of flow in seven rabbits (70%). None of the control groups showed significant restoration of retinal venous blood flow. CONCLUSIONS US-assisted thrombolysis using liposomes resulted in a statistically significant reperfusion of retinal vessels in the rabbit experimental model of RVO. This approach might be promising in the treatment of RVO in humans. Further studies are needed to evaluate this approach in patients with RVO. Ultrasound assisted thrombolysis can be an innovative tool in management of retinal vein occlusion.

Ultrasonic Doppler measurements of blood flow velocity of rabbit retinal vessels using a 45-MHz needle transducer

BackgroundThe purpose of this study is to measure blood flow velocity of rabbit retinal vessels using a 45-MHz ultrasonic Doppler system with a needle transducer.MethodsA high-frequency pulsed Doppler system that utilizes a 45-MHz PMN-PT needle transducer was developed to measure retinal blood flow velocity in situ. The pulsed Doppler allowed the differentiation of retinal from choroidal blood flow velocity. The needle transducer was inserted into the vitreous cavity through a 20-gauge incision port to access the retinal vessels. The first phase of the experiment evaluated the reproducibility of the measurements. The second phase measured velocities at four positions from the optic disc edge to the distal part of each vessel in nine eyes for the temporal and six eyes for the nasal portions. The angle between the transducer and the retinal vessel at each site was measured in enucleated rabbit eyes to estimate and compensate for measurement errors.ResultsIn the first phase, the average measurement error was 5.97 ± 1.34%. There was no significant difference comparing all eyes. In the second phase, the velocities gradually slowed from the disc edge to the distal part, and temporal velocities were faster than nasal velocities at all measurement sites.ConclusionThis study demonstrated the feasibility of reliably measuring retinal blood flow velocity using a 45-MHz ultrasonic Doppler system with a needle transducer.

NorLeu3A(1–7) Accelerates Clear Corneal Full Thickness Wound Healing

PURPOSE We evaluated the effect of the renin angiotensin system (RAS) peptide NorLeu3-Angiotensin (1-7) (NLE) formulated in a viscoelastic gel (USB004) on the healing of full-thickness corneal injuries. METHODS Dutch pigmented rabbits received conjunctival administration of 0.3% USB004, 0.03% USB004, or vehicle-control to healthy and full-thickness injured eyes administered once daily for 28 consecutive days. Safety was evaluated using IOP measurement, slit-lamp examination, and confocal microscopy. Evaluations for both efficacy studies included an oblique light examination, modified Seidel test (Seidel test with gentle ocular pressure) as well as during elevated IOP test, confocal microscopy imaging, and histologic analysis. RESULTS Application of 0.3% USB004, 0.03% USB004, and vehicle-control was safe in healthy and incised eyes. Further, application of 0.3% and 0.03% USB004 following full-thickness corneal incision resulted in a 2-fold acceleration of resolution of edema and inflammation, reduction in duration of wound leakage on a modified Seidel test (Seidel test with gentle ocular pressure) as well as during elevated IOP test, and healing with near normal architecture without evidence of fibrosis and angiogenesis when compared to vehicle-control animals. CONCLUSIONS Topical ocular application of 0.3% and 0.03% USB004 promotes full-thickness cornea wound healing without the evidence of fibrosis and angiogenesis. Further studies are warranted to determine the cornea-specific mechanism of action(s) that promotes regeneration leading to clear corneal healing.

High-Resolution OCT: An Innovative Tool for Posterior Segment Imaging

Optimal management of posterior segment disorders requires a high-resolution and preferably noninvasive imaging tool for better definition of diseases. High-resolution optical coherence tomography can provide noninvasive, high-definition imaging of the posterior segment, allowing earlier diagnosis, better follow-up of chronic cases, and more accurate and timely monitoring of the effect of therapeutic agents. Recent findings suggest an individualized approach to vitreoretinal and choroidal diseases is possible based not only on traditional ophthalmic investigations, but also on high-resolution optical coherence tomography. This innovative tool has the combined advantages of high speed, high resolution, and safe use.

Implantation of multiple suprachoroidal electrode arrays in rabbits

Purpose Epiretinal and subretinal prosthesis have been shown to be a valid way to provide some vision to patients with advanced outer retinal degeneration and profound vision loss. However, the field of vision for these patients is markedly limited by the area occupied by the electrode array. In this study, we aimed to evaluate the feasibility of implantation of multiple suprachoroidal electrode arrays in a single eye in order to increase the field of vision in patients implanted with retinal prosthesis. Methods The right eye of seventeen Dutch rabbits (age range, 5–6 months) was used for the study. Multiple inactive custom-made electrode arrays were inserted into the suprachoroidal space (SCS) and animals were followed up for up to 6 months using fundus photography, optical coherence tomography (OCT), and fluorescein angiography (FA). Results It was possible to surgically implant up to 8 electrode arrays in a single eye. None of the rabbits showed any major complications. The electrodes were well tolerated and remained in position in all rabbits. There was no evidence of retinal damage on follow-up exams and FA throughout the study. Conclusion Multiple suprachoroidal electrode array implantation is feasible and may provide a novel approach to increase the field of vision in subjects implanted with retinal prosthesis.