Kenan Sonmez

Targeting Tissue Factor for Immunotherapy of Choroidal Neovascularization by Intravitreal Delivery of Factor VII-Fc Chimeric Antibody

Purpose: ICON is a fusion protein composed of factor VII, the natural ligand for tissue factor, conjugated to the Fc domain of a human IgG1 immunoglobulin. It binds to the tissue factor expressed on neovascular endothelia and initiates a cytolytic immune attack that destroys the neovascular tissue. We previously showed that mouse factor VII-Fc chimeric antibody (mICON) dramatically decreases the frequency of choroidal neovascularization in a laser-induced choroidal neovascularization model in mice. Herein, we determined the safety and efficacy of mICON in destroying subretinal choroidal neovascularization in pig eyes. Methods: mICON (150–1200 μg) was administered into the midvitreous cavity of the pig eye either before (on Day 0) or after (on Day 10) induction of choroidal neovascularization with laser photocoagulation. On Day 14, the incidence of choroidal neovascularization was determined using confocal microscopy. We also determined the binding specificity (% binding to choroidal neovascularization/% binding to non-choroidal neovascularization areas) of mICON to tissue factor expressed on endothelial cells of laser-induced choroidal neovascularization. Results: We observed that mICON selectively destroyed choroidal neovascularization in a dose-dependent manner (r = −0.93; EDB50B = 571.3 μg). Obliteration of the choroidal neovascular complex was more prominent at doses > 300 μg (p < 0.05). No systemic or local complications (including retinal tear/detachment, inflammation, infection, cataract, or glaucoma) were observed. Binding specificities of hICON (2.2 ± 0.2) and mICON (3.4 ± 0.4) were significantly higher than that of anti-von Willebrand antibody (0.1 ± 0.01, p < 0.001). Conclusions: Both hICON and mICON bound to the neovascular endothelia of choroidal neovascularization with greater specificity than anti-von Willebrand antibody. Furthermore, mICON can selectively obliterate already established choroidal neovascularization, which suggests that it may be useful for immunotherapy in patients with exudative (wet) macular degeneration.

The role of macular hydration in the evaluation of the effect of intravitreal triamcinolone on visual acuity in eyes with diabetic macular edema

To evaluate the efficacy of intravitreal triamcinolone (IVTA) in eyes with clinically definite diabetic macular edema (DME) by using the parameters visual acuity (VA), central macular thickness (CMT) and macular hydration (MH). Medical records of patients who received IVTA (4xa0mg/0.1xa0mL) for DME were reviewed. Optically non-reflective areas which appear dark spaces within the 1000xa0μm from the center of the macula on OCT scan defined as MH. Best corrected logarithm of minimum angle of resolution (logMAR) visual acuity, CMT as determined by optical coherence tomography (OCT) and MH quantified from the OCT scans by using metamorph analysis were evaluated before the injection and at 1, 3 and 6xa0months in all, and up to 12xa0months in some eyes, after the IVTA injection. The correlations between these variables were also studied. 28 eyes of 27 patients were included in the study. Eyes with DME treated by a single IVTA injection responded with a trend towards significant improvement in logMAR VA at 1 (pxa0<xa00.0001) and 3xa0months (pxa0<xa00.0001), but no significant improvement in relation to baseline at 6xa0months was observed (pxa0=xa00.07). CMT was significantly reduced at 1xa0month (pxa0<xa00.0001), 3xa0months (pxa0<xa00.0001) and 6xa0months (pxa0=xa00.01) compared to baseline. Like the trend observed in VA improvement, MH also significantly reduced at 1xa0month (pxa0<xa00.0001) and 3xa0months (pxa0<xa00.0001), but not at 6xa0months (pxa0=xa00.14) compared to baseline. There was no correlation between the VA ratio and the CMT ratio (rxa0=xa00.18, pxa0=xa00.36), but there was a significant correlation between the VA ratio and the MH ratio (rxa0=xa00.85, pxa0<xa00.0001). There was also an inverse relationship between MH ratio and the age of the patients (rxa0=xa0−0.7089, pxa0=xa00.0001). Macular hydration seems to be a better parameter than macular thickness for determining the effectiveness of IVTA treatment in a subset of eyes with DME. Although the treatment effect is temporary, younger patients with DME were more prone to respond with a greater reduction in MH after IVTA injection.

Evaluation of corneal topographic changes and surgically induced astigmatism after transconjunctival 27-gauge microincision vitrectomy surgery

PurposeTo evaluate the corneal topographic changes and postvitrectomy astigmatism after 27-gauge (g) microincision vitrectomy surgery (MIVS) by using Pentacam HR-Scheimpflug imaging system.MethodsThis prospective descriptive study included 30 eyes of 30 patients who underwent 27-g MIVS. All eyes underwent a Pentacam HR examination preoperatively and on the first week, first month and third month postoperatively. The power of the corneal astigmatism, mean keratometry (Km), K1 and K2 values and corneal asphericity (Q value) values for the both front and back surfaces of the cornea, index of surface variance (ISV), index of vertical asymmetry (IVA), index of height asymmetry (IHA), index of height decentration (IHD) and higher-order aberrations including coma, trefoil, spherical aberration, higher-order root-mean-square and total RMS were recorded. Additionally, the mean induced astigmatism was estimated by vector analysis.ResultsNo statistically significant changes were observed in the mean power of corneal astigmatism, mean keratometry, K1 and K2 values, corneal asphericity values, ISV, IVA, IHA, IHD and higher-order aberrations on the first week, first month and third month after the operation. The mean surgically induced astigmatism was calculated as 0.23xa0±xa00.11 D on the first week, 0.19xa0±xa00.10 D on the first month and 0.19xa0±xa00.08 D on the third month postoperatively.ConclusionMinor corneal surface and induced astigmatic changes are expected to result in rapid visual rehabilitation after pars plana vitrectomy with the 27-g MIVS system.

Segmental Analysis of Macular Layers in Patients With Rhegmatogenous Retinal Detachment Treated With Perfluoropropane or Silicon Oil

BACKGROUND AND OBJECTIVEnTo determine possible changes in thickness profiles of retinal layers in patients with rhegmatogenous retinal detachment (RRD) treated with perfluoropropane (C3F8) or silicon oil (SiO).nnnPATIENTS AND METHODSnSeventy-two eyes of 36 patients were enrolled in this retrospective comparative study. Patients were divided into two groups according to intraocular tamponade: C3F8 or SiO. All study eyes were compared with fellow eyes via spectral-domain optical coherence tomography segment analysis at 6 months postoperatively. Macular layer thicknesses including retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium were analyzed.nnnRESULTSnThere was a statistically significant difference between eyes in terms of INL thickness (P = .044) in C3F8 group. Otherwise there was a statistically significant difference between eyes in terms of INL, OPL, and ONL thicknesses (P = .006, P = .048, and P = .004, respectively) in the SiO group.nnnCONCLUSIONnThe findings of the present study show that the tamponade used in RRD surgery can affect the retinal layers differently. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:41-47.].

Assessment of orbital blood flow velocities in retinopathy of prematurity

The purpose of this study is to evaluate whether the presence of any stage retinopathy of prematurity (ROP) alters central retinal artery (CRA) and ophthalmic artery (OA) blood flow parameters in premature infants. The patients were divided into two groups according to the development of ROP; those who have ROP were defined as group I, those without ROP were defined as group II. Ninety eyes of 45 patients in group I and 40 eyes of 20 patients in group II were investigated. The blood flows in the CRA and OA were measured using ultrasound color doppler imaging (CDI) that allows to evaluate the peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI). The results were compared between two groups of subjects. There were no significant differences in the PSV, EDV, and RI of CRA between two groups (Pxa0=xa00.09, Pxa0=xa00.20 and Pxa0=xa00.63, respectively). The mean PSV value of OA in group I was found to be significantly higher than the one in group II (Pxa0<xa00.05), but there were no significant differences in the mean EDV and RI values of OA between two groups (Pxa0=xa00.40, Pxa0=xa00.17 respectively). The subgroup analysis revealed that the ocular blood dynamics were not found to be significant between eyes with stage I ROP and eyes with stage II ROP (Pxa0>xa00.05), whereas the difference in the mean PSV values of OA were found to be significant among the eyes with stage 1 ROP, eyes with stage 2 ROP, and eyes without ROP (Pxa0=xa00.03). This study demonstrated significant alterations in systolic flow velocities in the OA predicted by CDI in infants with ROP.

Nd:YAG Laser Photodisruption for Multilevel Premacular Hemorrhage due to Isolated Retinal Venous Macroaneurysm

A 55-year-old man presented with sudden deterioration of vision in the right eye. His visual acuity was reduced to hand motion because of a large multilevel premacular hemorrhage. Nd:YAG laser was performed to drain the entrapped hemorrhage under the internal limiting membrane (ILM) and posterior hyaloid face in the macula into the vitreous. Immediately after laser treatment, streaming of red blood cells into the vitreous gel through the perforation site was observed. At the first-month follow-up, BCVA improved to 20/25 and ILM wrinkling was observed at the macula where the preretinal hemorrhage cleared. Fluorescein angiography revealed an isolated retinal venous macroaneurysm located on the macular branch of the superotemporal vein at the bifurcation site. In contrast to retinal arterial macroaneurysms, retinal venous macroaneurysms are quite rare. To the best of our knowledge, this is the first case reported with multilevel premacular hemorrhage caused by an isolated retinal venous macroaneurysm.