1: Ophthalmic Res. 2010 Feb 19;44(1):43-49 [Epub ahead of print] 

Effects of Bevacizumab on Apoptosis, Na-K(+)-Adenosine Triphosphatase and Zonula
Occludens 1 Expression on Cultured Corneal Endothelial Cells.

Yoeruek E, Tatar O, Spitzer MS, Saygili O, Biedermann T, Bartz-Schmidt KU,
Thaler S, Szurman P.

Department of Ophthalmology, Eberhard-Karl University, Tuebingen, Germany.

Background: This laboratory study was undertaken to investigate the influence of
bevacizumab on apoptosis, Na(+)-K(+)-adenosine triphosphatase
(Na(+)-K(+)-ATPase) and zonula occludens 1 (ZO-1) expression on cultured human
corneal endothelial cells (HCECs). Methods: Annexin V binding combined with
propidium iodide (PI) costaining was used to distinguish viable, early and late
apoptotic cells. Immunolocalization of ZO-1 and Na(+)-K(+)-ATPase was performed
to analyze intercellular cell integrity after exposure to 5.0 mg/ml bevacizumab
for 24 h. Results: No significant induction of apoptosis or necrosis was seen in
HCECs after exposure to 5.0 mg/ml bevacizumab (p = 0.689, p = 0.516,
respectively). The mean number of annexin-V-FITC- and PI-positive cells did not
change significantly. Additionally, no significant changes in expression were
detectable, neither for ZO-1 nor for Na(+)-K(+)-ATPase in comparison with the
control. For ZO-1, 70.0% of the cells stained intensely, 24.7% stained
moderately, and 5.3% stained weakly in the control group. After exposure to 5.0
mg bevacizumab, only minor changes were observable: 68.8% stained intensely,
25.4% moderately and 5.8% weakly (p = 0.524). For Na(+)-K(+)-ATPase, 19.3% of
the cells stained intensely, 59.4% moderately, and 21.3% weakly in the control
group. After exposure to 5.0 mg bevacizumab, again only minor changes were
observable in the expression pattern: 18.2% stained intensely, 60.3% moderately
and 21.5% weakly. The changes were not significant compared with the control (p
= 0.492). Conclusions: Bevacizumab, at concentrations used clinically, did not
induce apoptosis or necrosis in HCECs in vitro. Additionally, no alteration of
ZO-1 or Na(+)/K(+)-ATPase expression was detected after exposure to 5.0 mg/ml
bevacizumab for 24 h. Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20173357  [PubMed - as supplied by publisher]

2: Ophthalmic Res. 2010 Feb 17;44(1):34-42 [Epub ahead of print] 

Physical Changes in Human Meibum with Age as Measured by Infrared Spectroscopy.

Borchman D, Foulks GN, Yappert MC, Kakar S, Podoll N, Rychwalski P, Schwietz E.

Department of Ophthalmology and Visual Sciences, University of Louisville,
Louisville, Ky., USA.

Both lipids and mucins contribute to the stability of the tear film and lipids
may inhibit tears from evaporating. Younger people have lower lipid viscosity,
higher lipid volume, and a lower rate of tear evaporation. Since age-related
changes in human meibum composition and conformation have never been
investigated, as a basis for the study of lipid-associated changes with
meibomian gland dysfunction, we used the power of infrared spectroscopy to
characterize hydrocarbon chain conformation and packing in meibum from humans
without dry eye symptoms in relation to age and sex. Meibum from normal human
donors ranging in age from 3 to 88 years was studied. Meibum phase transitions
were quantified by fitting them to a 4-parameter 2-state sigmoidal equation.
Human meibum order and phase transition temperatures decrease with age and this
trend may be attributed to lipid compositional changes. If meibum has the same
thermodynamic properties on the surface of the tears as it does on the lid
margin, a decrease in lipid-lipid interaction strength with increasing age could
decrease the stability of tears since lipid-lipid interactions on the tear
surface must be broken for the tear film to break up. This study also serves as
a foundation to examine meibum conformational differences in meibum from people
with meibomian gland dysfunction. Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20160464  [PubMed - as supplied by publisher]

3: Ophthalmic Res. 2010 Feb 8;44(1):24-33 [Epub ahead of print] 

A Promising Therapeutic Approach for Treatment of Posterior Uveitis: Recombinant
T Cell Receptor Ligand Protects Lewis Rats from Acute and Recurrent Experimental
Autoimmune Uveitis.

Adamus G, Karren LJ, Mooney J, Burrows GG.

Ocular Immunology Laboratory, Department of Ophthalmology, Oregon Health and
Science University, Portland, Oreg., USA.

Introduction: Chronic autoimmune uveitis is a major cause of vision loss from
intraocular inflammation in humans. In this study we report that a recombinant
TCR ligand (RTL220) composed of the alpha1 and beta1 domains of MHC class II
molecules linked to the uveitogenic interphotoreceptor retinoid-binding protein
(IRBP) 1177-1191 peptide is effective in the suppression of acute and recurrent
experimental autoimmune uveitis (EAU). Material and Methods: EAU was induced
with IRBP1177-1191 peptide or by adoptive transfer of specific T cells in Lewis
rats. The rats received 5 doses of RTL220 subcutaneously every other day
starting at the onset of clinic signs of EAU. Results: The administration of
RTL220 resulted in a delayed onset and a significant amelioration of the disease
severity at clinical levels and showed protection of the retina from
inflammatory damage at histological levels. In treatment of recurrent EAU,
RTL220 administrated at the first or second onset of clinical disease
significantly inhibited EAU, modulated immune responses and provided protection
from relapses of uveitis. The systemic and local proinflammatory cytokines were
significantly reduced, including IL-17. There was local and systemic increase in
IL-10 and reduction in the expression of the proinflammatory chemokines CCL2,
CCL3 and CCL5. Conclusions: Our studies demonstrate a successful treatment of
acute and recurrent EAU with RTL220, which effectively suppressed the recurrence
of inflammation and reversed clinical and histological EAU by altering cytokine
and chemokine expression. These findings strongly support a possible clinical
application of this novel class of peptide/MHC class II drugs for patients with
autoimmune uveitis. Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20145422  [PubMed - as supplied by publisher]

4: Ophthalmic Res. 2010 Feb 3;44(1):17-23 [Epub ahead of print] 

Electrophysiological Retinal Pigment Epithelium Changes Observed with
Indocyanine Green, Trypan Blue and Triamcinolone.

Arndt C, Meunier I, Rebollo O, Martinenq C, Hamel C, Hattenbach LO.

Ophtalmologie, CHU de Montpellier, Montpellier, France.

Background: Intravitreal application of indocyanine green (ICG), trypan blue
(TB) or triamcinolone (TA) during vitreoretinal surgery has been associated with
severe damage to the retinal pigment epithelium (RPE). However, the
physiological background of these findings remains to be assessed. Methods: In
bovine RPE choroid preparations maintained in Ussing chambers, the effect of
apical application of ICG, TA (filtered and not filtered) and TB at different
concentrations was evaluated. The electrophysiological parameters
(transepithelial potential, tissular resistance and short-circuit current) were
continuously monitored. The experiments were conducted either in daylight or in
dark-adapted conditions. Results: After apical application of ICG and TA
(purified and not purified), all bioelectrical parameters were affected in a
dose-dependent manner. No significant changes were observed when the
preparations were exposed to daylight. No changes were observed with TB.
Conclusions: The electrophysiological results of apical application may explain
the toxic effects observed after intraoperative use of ICG and TA. In this RPE
study, TB appears to be the safest visualization aid for vitreoretinal surgery.
Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20130442  [PubMed - as supplied by publisher]

5: Ophthalmic Res. 2010 Feb 3;44(1):1-16 [Epub ahead of print] 

Applications of Nanobiotechnology in Ophthalmology - Part I.

Nguyen P, Meyyappan M, Yiu SC.

Department of Ophthalmology, Keck School of Medicine, University of Southern
California, Los Angeles, Calif., USA.

Much progress has been achieved in the field of nanotechnology and its
applications in ophthalmology. It is evident that drug delivery, gene therapy,
implantable devices and regenerative medicine are some of the key areas of
active research. To the best of our knowledge, there is limited review work on
this subject area in the current literature. To assist the interested clinicians
and scientists, this bipartite commentary will focus the discussion on emerging
researches in nano-ophthalmology and other enabling technologies that soon may
be available in the clinician's armamentarium to maintain and restore eye sight.
This installment will focus on recent discoveries in drug delivery, gene
therapy, imaging and visual prostheses; the second installment will discuss the
impact of nanotechnology on artificial environment, cell-nanostructure
interaction, other enabling nano-ophthalmic technologies, and safety and
biocompatibility of nanostructures. We will take this opportunity to introduce
some exciting nano-ophthalmic applications under investigation in our
laboratory. The accomplishments by the scientific community are tremendous and
the future prospects are wide open. Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20130441  [PubMed - as supplied by publisher]

6: Ophthalmic Res. 2010 Jan 15;43(4):185-192 [Epub ahead of print] 

Preparation and Clinical Evaluation of Succinylated Collagen Punctal Plugs in
Dry Eye Syndrome: A Pilot Study.

Hadassah J, Bhuvaneshwari N, Singh D, Sehgal PK.

BioProducts Laboratory, Central Leather Research Institute, Chennai, India.

Aim: This is a pilot study of 10 eyes of 6 patients. This paper describes the
preparation and clinical evaluation of succinylated collagen punctal plugs
(SCPP) in the treatment of dry eye syndrome (DES). Methods: SCPP were prepared
from succinylated collagen with the exact dimensions of the punctum (length
1.5-2.5 mm, diameter 0.2-0.5 mm, water content between 50 and 55%). All the
patients were clinically evaluated for best corrected visual acuity (BCVA), tear
fluid levels (TFL), protein content, tear fluid osmolarity (TFO), fluorescence
staining of the cornea and tear break-up time (TBUT) before and after punctal
occlusion with SCPP. Results: TFL improved among all the patients after punctal
occlusion with SCPP. BCVA showed improvement in case 4 (right eye/left eye),
case 5 (left eye) and case 6 (right eye), who had developed dry eyes due to
environmental conditions. Protein content increased on day 7 in all the patients
and gradually decreased. TFO decreased on days 3 and 5 in all patients after
punctal occlusion with SCPP, and showed the same levels on day 14. TFL, PC, TFO
and TBUT showed significant improvement in all the patients after punctal
occlusion with SCPP. Conclusion: All patients experienced symptomatic relief
after punctal occlusion with SCPP. There was no discomfort, foreign body
sensation, plug extrusion, corneal aberration, infection, or formation of
pyogenic granuloma with SCPP. SCPP stands as a promising alternative to other
punctal plugs in the treatment of DES. Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20090392  [PubMed - as supplied by publisher]

7: Ophthalmic Res. 2010 Jan 13;43(4):208-216 [Epub ahead of print] 

Excised Porcine Cornea Integrity Evaluation in an in vitro Model of
Iontophoretic Ocular Research.

Gratieri T, Gelfuso GM, Thomazini JA, Lopez RF.

Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of
Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.

Background/Aims: It is a challenge to adapt traditional in vitro diffusion
experiments to ocular tissue. Thus, the aim of this work was to present
experimental evidence on the integrity of the porcine cornea, barrier function
and maintenance of electrical properties for 6 h of experiment when the tissue
is mounted on an inexpensive and easy-to-use in vitro model for ocular
iontophoresis. Methods: A modified Franz diffusion cell containing two ports for
the insertion of the electrodes and a receiving compartment that does not need
gassing with carbogen was used in the studies. Corneal electron transmission
microscopy images were obtained, and diffusion experiments with fluorescent
markers were performed to examine the integrity of the barrier function. The
preservation of the negatively charged corneal epithelium was verified by the
determination of the electro-osmotic flow of a hydrophilic and non-ionized
molecule. Results: The diffusion cell was able to maintain the temperature,
homogenization, porcine epithelial corneal structure integrity, barrier function
and electrical characteristics throughout the 6 h of permeation experiment,
without requiring CO(2) gassing when the receiving chamber was filled with 25 mM
of HEPES buffer solution. Conclusion: The system described here is inexpensive,
easy to handle and reliable as an in vitro model for iontophoretic ocular
delivery studies. Copyright (c) 2010 S. Karger AG, Basel.

PMID: 20068374  [PubMed - as supplied by publisher]

8: Ophthalmic Res. 2010 Jan 6;43(4):201-207 [Epub ahead of print] 

Effect of Work-Related Ultraviolet Exposure and Ophthalmic Changes in Austrian
Farmers: The SVB-UV Study.

Schmid-Kubista KE, Kellner L, Maier H, Felke S, Wanka A, El Modeir A, Schmidt
JB, Cabaj A, Schmalwieser A, Rohn H, Stadelmann H, Spiess J, Fischer W,
Honigsmann H, Binder S.

Department of Ophthalmology, Ludwig Boltzmann Institute for Retinology and
Biomicroscopic Laser Surgery, Rudolf Foundation Clinic, Vienna, Austria.

Background: Epidemiological screening to examine possible ultraviolet-induced
ocular changes and pathologies in Austrian farmers. Methods: The study was
performed on behalf of the Austrian farmer insurance (Sozialversicherungsanstalt
der Bauern). Randomly selected farmers and office workers as controls, both at
the age of 35-55 years, underwent ophthalmic screening examinations. All
subjects underwent complete ophthalmic examinations by slit lamp examination and
Schirmer's test 1. A survey, regarding per- sonal habits in the sun, was also
conducted. Results: Three hundred and ninety-two subjects underwent ophthalmic
examinations of whom 297 were farmers and 95 were controls. Due to the survey,
89.7% of the farmers claimed to protect themselves from the sun during work.
From these subjects, 83.7% wear a head protection, 71.0% wear sunglasses, and
54.4% usually work in the shade. There were significant differences in lid (p =
0.021) and conjunctival pathologies (p < 0.0001) between farmers and controls.
Conclusion: Austrian farmers are at a higher risk for developing lid and
conjunctival tumours which require treatment at some point. We believe that the
study group was too young to show significant differences within the lens and
the posterior pole. A 5-year follow-up is planned. Copyright (c) 2010 S. Karger
AG, Basel.

PMID: 20068373  [PubMed - as supplied by publisher]

9: Ophthalmic Res. 2009 Dec 31;43(4):197-200 [Epub ahead of print] 

Evaluation of Plasma Glutamate Levels in Normal Tension Glaucoma.

Bunting H, Still R, Williams DR, Gravenor M, Austin MW.

Department of Ophthalmology, Singleton Hospital, Swansea, UK.

Aim/Background: Abnormal metabolism of the neurotransmitter glutamate is
implicated in a number of neurodegenerative conditions. Patients with migraine
have been shown to have elevated plasma glutamate levels. Migraine is a risk
factor both in terms of prevalence and progression in normal-tension glaucoma
(NTG). The aim of this study was to determine whether or not plasma glutamate
levels are also elevated in NTG. Methods: Patients were recruited into 2 groups,
NTG and control, according to inclusion and exclusion criteria. Patients with
migraine were excluded from both groups. Fasting blood samples were collected in
lithium heparin tubes, transported on ice, and centrifuged for storage at -21
degrees C. Plasma glutamate levels were measured by an amino acid analyser. Data
for each group were compared by applying the Mann-Whitney test. Ethical approval
and independent statistical advice for the study was obtained. Results: A total
of 27 subjects were recruited: 14 to the NTG group and 13 to the control group.
No significant difference was found between the plasma glutamate levels in the 2
groups (p = 0.67). Conclusion: Although an association between normal tension
and migraine is recognized, unlike studies in migraine sufferers, this study
finds no evidence that patients with NTG have elevated plasma glutamate.
Copyright (c) 2009 S. Karger AG, Basel.

PMID: 20068372  [PubMed - as supplied by publisher]

10: Ophthalmic Res. 2009 Dec 31;43(4):193-196 [Epub ahead of print] 

MTHFR C677T Homozygous Mutation in a Patient with Pigmentary Glaucoma and
Central Retinal Vein Occlusion.

Jaksic V, Markovic V, Milenkovic S, Stefanovic I, Jakovic N, Knezevic M.

Department of Ophthalmology, Faculty of Medicine, Kosovska Mitrovica, Belgrade,
Serbia.

Purpose: We present the rare case of a young male patient with asymmetric ocular
findings: pigmentary ocular hypertension associated with nonischemic central
retinal vein occlusion (CRVO) in the right eye and pigmentary glaucoma (PG) with
progressive glaucomatous optic damage in the left eye. Patients and Methods: A
31-year-old man showed nonischemic CRVO in the right eye and the clinical triad
of pigment dispersion syndrome in both eyes, however more marked in the left
eye. Best-corrected visual acuity was logMAR 0.3 in the right eye and 1.0 in the
left eye at presentation. The single risk for developing PG and CRVO was
hyperhomocysteinemia. The patient was a carrier of the methylenetetrahydrofolate
reductase C677 homozygous mutation. Results: At 18 months of follow-up, visual
acuity remained stable, intraocular pressure was in the normal range, but
retinal tomography indicated an increase in glaucomatous optic damage to the
nerve fiber layer in almost the complete temporal-inferior sector of the left
eye, but without visual field defects in the left eye. Retinal tomography and
automated perimetry were normal in the right eye. The patient received topical
antiglaucomatous therapy. Conclusion: Higher levels of plasma homocysteine, even
mildly elevated ones, could be associated with nonischemic CRVO and PG,
especially when related to genetic risk factors or C677T mutation. Copyright (c)
2009 S. Karger AG, Basel.

PMID: 20068371  [PubMed - as supplied by publisher]

11: Ophthalmic Res. 2009 Dec 31;43(4):179-184 [Epub ahead of print] 

Is the Insertional Anatomy of Rectus Extraocular Muscles Binocularly
Symmetrical?

Cho HK, Shin SY.

Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital,
College of Medicine, Catholic University of Korea, Seoul, Korea.

Purpose: This study was performed to examine the location, width, and
insertional shape of rectus extraocular muscles (EOMs), and to elucidate the
symmetry of the insertional anatomy of rectus EOMs in the left and right eyes.
Methods: EOMs were dissected from their origin to the insertion point in 100
intact orbits of 50 cadavers. The width, location, and shape of 4 rectus EOMs
insertions were measured. The insertional shapes were classified into 6
categories: straight, oblique, convex, oblique-convex, concave, and nonspecific
types. Results: The most common types of insertional shapes were superior rectus
muscle, oblique type (34%); inferior rectus muscle, oblique type (7%); lateral
rectus muscle, concave type (41%); and medial rectus muscle, straight type
(37%). The distance from the limbus to insertion and the width of rectus EOMs
were almost symmetrical between the left and right eyes of the paired specimens.
However, the insertional shapes were different in 46% of the superior rectus,
56% of the inferior rectus, 58% of the lateral rectus, and 46% of the medial
rectus muscles. In a given individual, 49 individuals demonstrated asymmetric
insertional shapes in at least 1 rectus EOM in both eyes. Conclusions: Ocular
surgeons should consider the possibility of differences in the insertional shape
of rectus EOMs between the left and right eyes, especially when performing
rectus EOM recession. Copyright (c) 2009 S. Karger AG, Basel.

PMID: 20068370  [PubMed - as supplied by publisher]

12: Ophthalmic Res. 2009 Dec 31;43(4):173-178 [Epub ahead of print] 

Fluid Temperature at the Corneal Endothelium during Phacoemulsification:
Comparison of an Ophthalmic Viscosurgical Device and Balanced Salt Solution
Using the Finite Element Method.

Reepolmaha S, Limtrakarn W, Uthaisang-Tanechpongtamb W, Dechaumphai P.

Department of Ophthalmology, Faculty of Medicine, Srinakharinwirot University,
Bangkok, Thailand.

Purpose: The purpose of this study was to estimate and compare the temperatures
of two different anterior chamber solutions at the corneal endothelial level
during phacoemulsification. An ophthalmic viscosurgical device (OVD) and
balanced salt solution (BSS) were compared using the finite element method
(FEM). Materials and Methods: The thermal properties of an OVD (IAL-F) and BSS
were studied in an experimental setting. A computer-aided design model of ocular
anatomy was created in two dimensions. The phaco needle was considered to be the
only source of heat generation. Then, the FEM was used to demonstrate the
transient temperature distribution in the two ocular models at 10, 20, 30, 40,
50 and 60 s. In these models, the anterior chamber was filled with IAL-F (IAL-F
model) or BSS (BSS model). Results: The heat generation rate of the phaco needle
was 0.0004 cal/s/mm(2). The maximum corneal endothelial temperatures for the two
models at 60 s were 52.67 and 41.57 degrees C, respectively. The experimental
IAL-F model showed fewer changes in temperature for any given time and location.
At larger distances from the heat source, less temperature variation was
detected. Conclusion: Phacoemulsification is a potential heat-generating
procedure performed between the delicate anterior chamber structures. During
this procedure, IAL-F protects the endothelium against heat better than BSS.
Copyright (c) 2009 S. Karger AG, Basel.

PMID: 20068369  [PubMed - as supplied by publisher]

13: Ophthalmic Res. 2009 Dec 31;43(4):169-172 [Epub ahead of print] 

Increased Oxidative Stress in Patients with Pseudoexfoliation Syndrome.

Cumurcu T, Gunduz A, Ozyurt H, Nurcin H, Atis O, Egri M.

Department of Ophthalmology, Gaziosmanpasa University School of Medicine, Tokat,
Turkey.

Purpose: The objective of this study was to investigate the antioxidant/oxidant
status of serum in patients with pseudoexfoliation syndrome (PEX). Methods:
Forty-seven patients with PEX and 32 healthy controls were included in the
study. Serum total antioxidant capacity (TAC) and total oxidant status (TOS)
levels were determined by using a novel automated method. Results: A significant
increase in serum TOS (p < 0.001) and a significant decrease in serum TAC (p <
0.0001) were observed in PEX patients compared to control subjects. Conclusion:
TAC decreases while the oxidative stress increases in PEX. Copyright (c) 2009 S.
Karger AG, Basel.

PMID: 20068368  [PubMed - as supplied by publisher]

14: Ophthalmic Res. 2010;43(3):159-68. Epub 2009 Dec 31. 

The in vitro study of pressure change effect on corneal birefringence.

Xiao Z, Wang C, Hao YS.

The Peking University Third Hospital, Peking University Eye Center, Beijing,
China.

PURPOSE: To study the change of corneal birefringence at different pressures in
vitro to determine whether corneal birefringence changes along with pressure.
METHODS: The pattern of corneal birefringence was recorded at different
intraocular pressures. The pressure differences were 0.10, 0.50 and 1.00 mm Hg,
respectively. To compare the pattern sequence at two pressure values, a
nonpaired t test was performed. RESULTS: Statistical analysis indicates that the
difference of the corneal birefringence is significant when the pressure
difference was more than 0.50 mm Hg in polarized light. CONCLUSION: The results
of corneal photoelasticity in vitro demonstrate that the change in pressure on
the cornea leads to a change in corneal birefringence. Copyright 2009 S. Karger
AG, Basel.

PMID: 20068367  [PubMed - in process]