Einhorn Clinical Research Center

New York City, NY, United States

Einhorn Clinical Research Center

New York City, NY, United States
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Zarbin M.A.,University of Bergen | Montemagno C.,University of Cincinnati | Leary J.F.,Purdue University | Ritch R.,Einhorn Clinical Research Center
Current Opinion in Pharmacology | Year: 2013

The earliest impact of nanomedicine in ophthalmology is likely to involve the areas of biopharmaceuticals, implantable materials (e.g. tissue regeneration scaffolds, bioresorbable materials), implantable devices (e.g. glaucoma drainage valves), and diagnostic tools (e.g. intraocular pressure (IOP) monitors). Nanotechnology will bring about the development of regenerative medicine (i.e. replacement and improvement of cells, tissues, and organs) and artificial vision. In this chapter, we review ophthalmic applications of nanotechnology in the following areas: drug and trophic factor therapy for glaucoma, retinal degenerative, and retinal vascular disease; gene therapy for retinal degenerative disease; regenerative medicine, including optogenetics and optic nerve regeneration; and diagnostics (minimally invasive IOP monitoring). Nanotechnology will play an important role in both early-stage and late-stage intervention in the management of blinding diseases. © 2012 Elsevier Ltd.

Jonas J.B.,University of Heidelberg | Ritch R.,Einhorn Clinical Research Center | Panda-Jonas S.,University of Heidelberg
Progress in brain research | Year: 2015

The optic nerve head forms the interface between the intraocular compartment and the retrobulbar compartment. The former is characterized by what we term intraocular pressure (IOP) and the latter by orbital cerebrospinal fluid pressure (CSFP). The trans-lamina cribrosa pressure difference (TLCPD) is defined as the difference between the pressures in the two compartments. Any change in one of them can be associated with a disturbance of homeostasis of the optic nerve head, such as papilledema or glaucomatous optic neuropathy. In particular, glaucomatous optic neuropathy may be due to either an elevated IOP and/or an abnormally low orbital CSFP, or due to a change in the time-dependent relationship between the pulse-synchronous changes in IOP and orbital CSFP. Based on the triangular relationships between IOP, CSFP, and blood pressure, glaucoma may be described as an imbalance between these three pressure parameters, eventually leading to an increased TLCPD. Because the retinal and choroidal venous blood drains through the CSFP space, elevated CSFP may be associated with dilated retinal veins, increased incidence of retinal vein occlusions, higher prevalence and severity of diabetic retinopathy, and thicker choroid. © 2015 Elsevier B.V. All rights reserved.

Krupin T.,Northwestern University | Krupin T.,Chicago Center for Vision Research | Krupin T.,Devers Eye Institute | Liebmann J.M.,New York University | And 4 more authors.
American Journal of Ophthalmology | Year: 2011

Purpose: To compare the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% in preserving visual function in low-pressure glaucoma. Design Randomized, double-masked, multicenter clinical trial. Methods Exclusion criteria included untreated intraocular pressure (IOP) >21 mm Hg, visual field mean deviation worse than -16 decibels, or contraindications to study medications. Both eyes received twice-daily monotherapy randomized in blocks of 7 (4 brimonidine to 3 timolol). Standard automated perimetry and tonometry were performed at 4-month intervals. Main outcome measure was field progression in either eye, defined as the same 3 or more points with a negative slope <-1 dB/year at P < 5%, on 3 consecutive tests, assessed by pointwise linear regression. Secondary outcome measures were progression based on glaucoma change probability maps (GCPM) of pattern deviation and the 3-omitting method for pointwise linear regression. Results Ninety-nine patients were randomized to brimonidine and 79 to timolol. Mean (± SE) months of follow-up for all patients was 30.0 ± 2. Statistically fewer brimonidine-treated patients (9, 9.1%) had visual field progression by pointwise linear regression than timolol-treated patients (31, 39.2%, log-rank 12.4, P = .001). Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine-treated (28, 28.3%) than timolol-treated (9, 11.4%) patients discontinued study participation because of drug-related adverse events (P = .008). Similar differences in progression were observed when analyzed by GCPM and the 3-omitting method. Conclusion Low-pressure glaucoma patients treated with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%. © 2011 Elsevier Inc. All rights reserved.

Kim K.N.,Chungnam National University | Jeoung J.W.,Seoul National University | Park K.H.,Seoul National University | Kim D.M.,Seoul National University | And 2 more authors.
American Journal of Ophthalmology | Year: 2014

Purpose To investigate the relationship between preferred sleeping position and asymmetric visual field (VF) loss in open-angle glaucoma (OAG) patients. Design Retrospective, cross-sectional study. Methods Six hundred and ninety-two (692) patients with bilateral normal-tension glaucoma (NTG) or high-tension glaucoma were consecutively enrolled. A questionnaire to determine the preferred sleeping position was administered to each patient. Asymmetric VF loss was defined as a difference in mean deviation between the 2 eyes of at least 2 dB. According to these values, the better eye and worse eye were defined. Among the patients with asymmetric VF loss, the numbers preferring the worse eye-dependent lateral decubitus position and the better eye-dependent lateral decubitus position were compared. Results Among the enrolled patients, 309 (60.6%) with NTG and 121 (66.5%) with high-tension glaucoma had asymmetric VF between the 2 eyes. Among the 309 NTG patients, 100 (32.4%) preferred the lateral decubitus position. Of these, 66 (66.0%) preferred the worse eye-dependent lateral decubitus position (P =.001). Among the 121 high-tension glaucoma patients, 32 (26.4%) preferred the lateral decubitus position, and of these, 23 (71.9%) preferred the worse eye-dependent lateral decubitus position (P =.013). Conclusion Our results suggest that the sleep position habitually preferred by glaucoma patients may be associated with greater VF loss.

Hood D.C.,Columbia University | Raza A.S.,Columbia University | de Moraes C.G.V.,Einhorn Clinical Research Center | de Moraes C.G.V.,New York University | And 4 more authors.
Progress in Retinal and Eye Research | Year: 2013

There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test. © 2012 Elsevier Ltd.

Thonginnetra O.,Einhorn Clinical Research Center
Journal of glaucoma | Year: 2010

To compare visual field defects obtained with both multifocal visual evoked potential (mfVEP) and Humphrey visual field (HVF) techniques to topographic optic disc measurements in patients with normal tension glaucoma (NTG) and high tension glaucoma (HTG). We studied 32 patients with NTG and 32 with HTG. All patients had reliable 24-2 HVFs with a mean deviation of -10 dB or better, a glaucomatous optic disc and an abnormal HVF in at least 1 eye. Multifocal VEPs were obtained from each eye and probability plots created. The mfVEP and HVF probability plots were divided into a central 10-degree radius and an outer arcuate subfield in both superior and inferior hemifields. Cluster analyses and counts of abnormal points were performed in each subfield. Optic disc images were obtained with the Heidelberg Retina Tomograph III. Eleven stereometric parameters were calculated. Moorfields regression analysis and the glaucoma probability score were performed. There were no significant differences in mean deviation and pattern standard deviation values between NTG and HTG eyes. However, NTG eyes had a higher percentage of abnormal test points and clusters of abnormal points in the central subfields on both mfVEP and HVF than HTG eyes. For Heidelberg Retina Tomograph III, there were no significant differences in the 11 stereometric parameters or in the Moorfields regression analysis and glaucoma probability score analyses of the optic disc images. The visual field data suggest more localized and central defects for NTG than HTG.

Jonas J.B.,University of Heidelberg | Jonas J.B.,Capital Medical University | Wang N.,Capital Medical University | Yang D.,Capital Medical University | And 2 more authors.
Progress in Retinal and Eye Research | Year: 2015

The orbital cerebrospinal fluid pressure (CSFP) represents the true counter-pressure against the intraocular pressure (IOP) across the lamina cribrosa and is, therefore, one of the two determinants of the trans-lamina cribrosa pressure difference (TLPD). From this anatomic point of view, an elevated TLPD could be due to elevated IOP or abnormally low orbital CSFP. Both experimental and clinical studies have suggested that a low CSFP could be associated with glaucomatous optic neuropathy in normal-pressure glaucoma. These included monkey studies with an experimental long-term reduction in CSFP, and clinical retrospective and prospective studies on patients with normal-pressure glaucoma. Since the choroidal blood drains via the vortex veins through the superior ophthalmic vein into the intracranial cavernous sinus, anatomy suggests that the CSFP could influence choroidal thickness. A population-based study revealed that thicker subfoveal choroidal thickness was associated with higher CSFP. Since the central retinal vein passes through the orbital CSF space, anatomy suggests that the retinal venous pressure should be at least as high as the orbital CSFP. Other experimental, clinical or population-based studies suggested an association between higher CSFP and higher retinal venous pressure and wider retinal veins. Consequently, a higher estimated CSFP was associated with arterial hypertensive retinopathy (with respect to the dilated retinal vein diameter and higher arterial-to-venous diameter) and with the prevalence, severity and incidence of diabetic retinopathy. Physiologically, CSFP was related with higher IOP. The influence of the CSFP on the episcleral venous pressure and/or a regulation of both CSFP and IOP by a center in the dorsomedial/perifornical hypothalamus may be responsible for this. Insummary, the CSFP may be an overlooked parameter in ocular physiology and pathology. Abnormal changes in the CSFP, in particular in relationship to the IOP, may have pathophysiologic importance. © 2015 Elsevier Ltd.

Ritch R.,Einhorn Clinical Research Center
Journal of Glaucoma | Year: 2014

Exfoliation syndrome is an age-related disease characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues. It leads to the most common identifiable cause of open-angle glaucoma worldwide, comprising the majority of glaucoma in some countries. The material in the eye appears as white deposits on the anterior lens surface and/or pupillary border. During pupillary movement, the iris scrapes exfoliation material from the lens surface, while the material on the lens causes rupture of iris pigment epithelial cells, with concomitant pigment dispersion into the anterior chamber and its deposition on anterior chamber structures. Exfoliation material can be found in many different organs. It is an ischemic disease and is associated with elevated serum homocysteine. Systemic associations include transient ischemic attacks, hypertension, angina, myocardial infarction, cerebrovascular and cardiovascular disease, aortic aneurysm, Alzheimer disease, and hearing loss. The discovery in 2007 of nonsynonymous single nucleotide polymorphisms in the LOXL1 (lysyl oxidase-like 1) gene are expected to make a major impact not only in understanding exfoliation syndrome, but in leading to new avenues of therapy. Copyright © 2014 by Lippincott Williams & Wilkins.

Park S.C.,Einhorn Clinical Research Center
Investigative ophthalmology & visual science | Year: 2013

To assess factors associated with focal lamina cribrosa (LC) defects in glaucoma. Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head were obtained from glaucoma patients. EDI OCT scans were reviewed for focal LC defects (laminar holes or disinsertions). Evaluated clinical factors included age, central corneal thickness, visual field (VF) mean deviation (MD), exfoliation syndrome, normal-tension glaucoma (NTG), disc hemorrhage, and intraocular pressure (IOP) during past follow-up. One hundred forty-eight glaucomatous eyes (148 patients; mean age, 68 ± 12 years; mean VF MD, -11.63 ± 6.96 dB) were included. Sixty-seven (45%) eyes had focal LC defects and 81 (55%) did not. Eyes with focal LC defects had a higher prevalence of both disc hemorrhage (25% vs. 6%) and NTG (33% vs. 9%) and worse VF MD (-14.12 vs. -9.58 dB) than those without focal LC defects (P = 0.002, P < 0.001, and P < 0.001, respectively). In the multivariate logistic regression analysis, higher frequency of disc hemorrhage detection (odds ratio [OR], 3.63; P = 0.032), a diagnosis of NTG (OR, 4.23; P = 0.005), and worse VF MD (OR, 1.11; P < 0.001) were significant factors associated with the presence of focal LC defects. Disc hemorrhage developed in the same half of the disc as the largest or the second largest focal LC defect in 15 of 17 eyes (88.2%). Disc hemorrhage, a diagnosis of NTG, and more advanced glaucoma status are associated with focal LC defects. Future studies are needed to elucidate the cause-and-effect relationships between focal LC defects and these factors.

De Moraes C.G.,New York University | De Moraes C.G.,Einhorn Clinical Research Center
Journal of Glaucoma | Year: 2013

The axons of the retinal ganglion cells form the optic nerve. The two optic nerves meet at the optic chiasm, where the nerve fibers originating in the nasal retina of each eye decussate to join the temporal fibers of the fellow eye. From the chiasm, the same axons continue on as the optic tract. These axons travel to and synapse in the lateral geniculate nucleus, the cells of which send their axons through the optic radiations to the visual cortex. The main blood supply to visual cortex is provided by the posterior cerebral arteries and their branches (the calcarine, posterior temporal, and parieto-occipital arteries). At the occipital pole, however, there may be a dual blood supply to the area subserving central vision, with anastomoses between branches of the posterior cerebral arteries and the superior temporo-occipital branch from the middle cerebral artery. Copyright © 2013 by Lippincott Williams & Wilkins.

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