1: Br J Ophthalmol. 2008 May 6; [Epub ahead of print] 

Does orally administered soxycycline reach the tear film.

Smith VA, Khan-Lim D, Anderson L, Cook SD, Dick AD.

United Kingdom.

Background / aims - Orally administered doxycycline, a broad spectrum
antibiotic, is an established treatment for ocular surface diseases,
particularly rosacea, meibomian gland dysfunction and recurrent epithelial cell
erosion. In recent times its efficacy in treating these diseases has been
ascribed to an ability to inhibit matrix metalloproteinase (MMP) activity and
both MMP and interleukin-1 (IL-1) synthesis. Since these functions are
concentration dependent, the aim of this project was to determine whether
sufficient doxycycline reached the tear film to fulfil these roles in vivo.
Methods - Doxycycline was extracted with 1-butanol from tear and blood plasma
samples obtained from patients with ocular surface disease and healthy
individuals and quantified spectrophotometrically. The MMPs present in the
patients tear films before and during doxycycline treatment were analysed
zymographically. Results - The quantity of doxycycline detected in the blood
plasma samples of patients undergoing treatment ranged from 1.83-13.18microM.
Although doxycycline was was not detected in their tear samples, the treatment
caused the disappearance of the MMPs symptomatic of disease progression.
Conclusion - The inability to detect doxycycline in the tear film of patients
undergoing treatment indicates that doxycycline does not directly inhibit MMP
activity or the synthesis /secretion of these proteases and IL-1 from corneal
epithelial cells.

PMID: 18460541 [PubMed - as supplied by publisher]

2: Br J Ophthalmol. 2008 May 6; [Epub ahead of print] 

A Guide to the Removal of Heavy Silicone Oil.

Stappler T, Williams R, Gibran SK, Liazos E, Wong D.

United Kingdom.

Purpose: Heavy silicone oil removal can be challenging and differs considerably
from conventional oil. Traditionally, strong active aspiration had to be applied
through a long 18G needle just above the optic disc. We present a novel
technique using a much shorter (7.5mm) and smaller (20G) needle allowing its
removal "from a distance". Method: Active aspiration on a vacuum of 600mmHg of
the "viscous fluid injector" was applied using the 20G cannula in a
polymethylmethacrylate model eye chamber that was surface-modified to mimic the
surface properties of the retina. Measurements were taken using still
photographs. Results: Under injection the maximum diameter of a silicone oil
bubble supported by interfacial tension alone was 5mm for a steel and 7mm for a
polyurethane cannula. Under suction, the silicone bubble changed shape and
became conical thus further increasing the cannula\'s reach. This conical shape
illustrated "tubeless siphoning", which is a physical property of non-Newtonian
fluids. Discussion: The use of shorter and smaller gauge cannula for removal of
Densiron obviates the need to enlarge the sclerotomy beyond 20G or to apply
suction in close proximity to disc and fovea. This potentially reduces the risk
of iatrogenic damage such as entry site tears or postoperative hypotony.

PMID: 18460540 [PubMed - as supplied by publisher]

3: Br J Ophthalmol. 2008 May 6; [Epub ahead of print] 

Efficacy of antiglaucoma fixed combination therapy versus unfixed components in
reducing intraocular pressure: a systematic review.

Cox J Ba Hons M, Mollan SP Mbchb Mrco, Bankart J Ba Hons, Robinson R Frcophth F.

United Kingdom.

Aim To evaluate the efficacy of the fixed combination ocular hypotensive
therapies compared to their non-fixed components used concomitantly for lowering
intraocular pressure (IOP) in glaucoma and ocular hypertension. Methods A
systematic review of the literature, up to May 2007, without limits on year or
language of publication was performed. Seven randomised controlled trials
(n=2,083 eyes) were identified. Assessment of methodological quality was made
using standardised criteria. Results were pooled quantitatively using
meta-analysis methods and statistical analysis was performed using STATA(R)
software. The difference in mean intraocular pressure (mmHg) from baseline
between the fixed combination and non-fixed component therapies was compared.
Non-inferiority in terms of efficacy was set at an upper confidence limit of
4 months. Surface alkylation led
to dramatically increased intravitreal stability and slow degradation. The
estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks
(oxidised particles) and to 16 weeks (hydrosilylated particles). CONCLUSION: The
porous silicon photonic crystals showed good biocompatibility and may be used as
an intraocular drug-delivery system. The intravitreal injectable porous silicon
photonic crystals may be engineered to host a variety of therapeutics and
achieve controlled drug release over long periods of time to treat chronic
vitreoretinal diseases.

Publication Types:
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov\'t
    Research Support, U.S. Gov\'t, Non-P.H.S.

PMID: 18441177 [PubMed - in process]

24: Br J Ophthalmol. 2008 May;92(5):699-704. 

Circulating fibrocytes contribute to the myofibroblast population in
proliferative vitreoretinopathy epiretinal membranes.

Abu El-Asrar AM, Struyf S, Van Damme J, Geboes K.

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh,
Saudi Arabia. abuasrar@ksu.edu.sa

BACKGROUND/AIMS: Fibrocytes, circulating cells that co-express markers of
haematopoietic stem cells, leucocytes and fibroblast products, traffic to sites
of tissue injury, differentiate into myofibroblasts and contribute to wound
healing and fibrosis. We investigated the presence of fibrocytes and the
expression of their chemotactic pathways CCL21/CCR7 and CXCL12/CXCR4 in
proliferative vitreoretinopathy (PVR) epiretinal membranes. METHODS: Sixteen
membranes were studied by immunohistochemical techniques. RESULTS: Cells
expressing alpha-smooth-muscle actin (alpha-SMA), a marker of differentiation of
fibrocytes into myofibroblasts, were present in all membranes. Cells expressing
the haematopoietic stem-cell antigen CD34, the leucocyte common antigen CD45,
CCR7, CXCR4, CCL21 and CXCL12 were noted in 50%, 75%, 68.8%, 100%, 80% and 93.8%
of the membranes, respectively. Double immunohistochemistry indicated that all
cells expressing CD34, CD45, CCR7, CXCR4, CCL21 and CXCL12 co-expressed
alpha-SMA. The number of cells expressing CD34 correlated significantly with the
numbers of cells expressing CXCL12 (r(s) = 0.567; p = 0.022) and CCL21 (r(s) =
0.534; p = 0.04). CONCLUSIONS: Circulating fibrocytes may function as precursors
of myofibroblasts in PVR membranes.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 18441176 [PubMed - in process]

25: Br J Ophthalmol. 2008 May;92(5):694-8. 

Lack of inducible nitric oxide synthases attenuates leukocyte-endothelial cell
interactions in retinal microcirculation.

Iwama D, Miyahara S, Tamura H, Miyamoto K, Hirose F, Yoshimura N.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate
School of Medicine, Kyoto, 606-8507, Japan.

AIM: To investigate the effect of inducible nitric oxide synthases (iNOS) on
inflammatory reactions during endotoxin-induced uveitis (EIU) in mice by
studying leukocyte-endothelial cell interactions. METHODS: EIU was produced in
immunosuppressed iNOS(-/-) mice and C57BL/6 (normal) mice by footpad injection
of lipopolysaccharide. Leukocytes were labelled with acridine orange. Leukocyte
rolling in the retinal microcirculation was evaluated in vivo with acridine
orange digital fluorography. The number of migrated leukocytes was counted in
flat-mounted retina. RESULTS: Both leukocyte rolling and migration peaked at 48
h after lipopolysaccharide injection. The maximal numbers of rolling leukocytes
in the immunosuppressed iNOS(-/-) mouse retina decreased by 98.2% (p<0.001)
compared with that in the normal mouse retina at 48 h after lipopolysaccharide
injection. In addition, the maximal numbers of migrated leukocytes in the
immunosuppressed iNOS(-/-) mouse retina decreased by 74.0% (p<0.001) compared
with that in the normal mouse retina at 24 h after lipopolysaccharide injection.
Furthermore, the diameters of major retinal veins of the immunosuppressed
iNOS(-/-) group were smaller at both 24 and 48 h after lipopolysaccharide
injection than were those of the normal group (p<0.001, respectively).
CONCLUSIONS: A lack of iNOS suppresses leukocyte-endothelial cell interactions
in the retinas of mice with EIU. This suggests that iNOS may play a role in the
management of patients with uveitis and other inflammatory conditions.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 18441175 [PubMed - in process]

26: Br J Ophthalmol. 2008 May;92(5):640-4. 

Optical coherence tomography predictive factors for macular hole surgery
outcome.

Ruiz-Moreno JM, Staicu C, Pinero DP, Montero J, Lugo F, Amat P.

Albacete Medical School, University of Castilla La Mancha, Albacete, Spain.

AIM: To evaluate the use of preoperative optical coherence tomography (OCT)
findings as predictive factors for macular hole (MH) surgery outcomes. METHODS:
46 eyes from 46 patients with a diagnosis of MH were included in this study. In
all cases, a pars plana 25-gauge vitrectomy with peeling of the internal
limiting membrane was performed. Before and after surgery, a complete clinical
examination and a detailed macular analysis, which included the MH minimum and
base diameter, the MH height, the Macular Hole Index (MHI), Diameter Hole Index
(DHI) and Tractional Hole Index (THI), were performed. Predictive factors for
visual prognosis after surgery were obtained by receiver operating
characteristic curve analysis. RESULTS: Minimum and base diameter as well as THI
and MHI correlated significantly (p<0.01, p = 0.01, p = 0.04, p = 0.03,
respectively) with postoperative best spectacle corrected visual acuity at 3
months, but DHI and MH height did not. Cut-off values of 311 microm and 1.41
were obtained for the minimum diameter and THI, respectively, from receiver
operating characteristic curve analysis, providing an acceptable sensitivity and
specificity. CONCLUSION: An MH minimum diameter of <311 microm or a THI >1.41
are predictive factors for a good visual prognosis after MH surgery.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 18441174 [PubMed - in process]

27: Br J Ophthalmol. 2008 May;92(5):630-4. 

Age-related maculopathy and sunlight exposure evaluated by objective
measurement.

Hirakawa M, Tanaka M, Tanaka Y, Okubo A, Koriyama C, Tsuji M, Akiba S, Miyamoto
K, Hillebrand G, Yamashita T, Sakamoto T.

Department of Ophthalmology, Kagoshima University Graduate School of Medical and
Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

AIM: To study the relationship between age-related maculopathy (ARM) and
exposure to sunlight using an objective method. METHODS: In a case-control study
of Japanese men aged > or = 50 years (67 controls without ophthalmic disease and
148 with ARM), those with ARM were separated into groups of early (n = 75) and
late (n = 73) ARM. Facial wrinkle length and area of hyperpigmentation, which
are considered to be associated with exposure to sun, were measured using
imaging with computer-based image analysis. Skin tone was also measured on the
upper inner arm, which is not exposed to sun. Early and late ARM association
with skin measurements was then evaluated. RESULTS: Significantly more facial
wrinkling (p = 0.047, odds ratio 3.8; 95% CI 1.01 to 13.97) and less facial
hyperpigmentation (p = 0.035, odds ratio 0.3; 95% CI 0.08 to 0.92) was present
in late ARM cases. The relationship between skin tone and ARM risk was not
statistically significant. CONCLUSIONS: This objective method showed that
lifetime exposure to sunlight is an important factor in the progression of late
ARM. An individual\'s reaction to sunlight exposure may have a role in ARM
progression in addition to total lifetime exposure to sunlight.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 18441173 [PubMed - in process]

28: Br J Ophthalmol. 2008 May;92(5):623-9. 

Characterisation of the macular dystrophy in patients with the A3243G
mitochondrial DNA point mutation with fundus autofluorescence.

Rath PP, Jenkins S, Michaelides M, Smith A, Sweeney MG, Davis MB, Fitzke FW,
Bird AC.

Moorfields Eye Hospital, London, UK. prprath@yahoo.com

INTRODUCTION: The mitochondrial DNA A3243G point mutation is associated with a
wide variety of systemic manifestations including a macular dystrophy. The
characteristics of fundus autofluorescence (AF) in these patients are
distinctive and have not been previously described. METHODS: A complete history
and ophthalmic examination, including fundus photography and autofluorescence
imaging, was performed on twelve probands harbouring the A3243G point mutation.
RESULTS: Four patients had diabetes, 10/12 hearing loss, and 7/12 were visually
symptomatic. A positive family history was present in 5/12. Fundus findings
consisted of two primary phenotypes: discontinuous circumferentially oriented
perifoveal atrophy (9/12) or an appearance consistent with pattern dystrophy
(3/12). In both phenotypes pale deposits and pigment clumping were seen at the
level of the retinal pigment epithelium, with occasional changes also noted
outside the arcades and nasal to the optic nerve. Fundus AF imaging revealed
decreased autofluorescence in areas of atrophy and increased AF of the pale
subretinal deposits. In areas of the retina that appeared normal clinically,
variable sized flecks of increased and decreased AF were present. CONCLUSIONS:
The mitochondrial DNA A3243G point mutation can result in disease with a
variable presentation. Fundus autofluorescence reveals a recognisable phenotype
in most cases that is different from other macular dystrophies.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 18441172 [PubMed - in process]

29: Br J Ophthalmol. 2008 May;92(5):617-22. 

Autofluorescence of choroidal melanoma in 51 cases.

Shields CL, Bianciotto C, Pirondini C, Materin MA, Harmon SA, Shields JA.

Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street,
Philadelphia, PA 19107, USA. carol.shields@shieldsoncology.com

AIM: To describe the autofluorescence features of choroidal melanoma. DESIGN:
Non-comparative case series. PARTICIPANTS: 51 consecutive patients. METHODS:
Standard fundus photography and autofluorescence photography (580 nm excitation,
695 nm barrier filter) were performed on all patients. Clinical features were
correlated with autofluorescence features. MAIN OUTCOME MEASURE:
Autofluorescence features of choroidal melanoma and overlying retinal pigment
epithelium (RPE). RESULTS: The mean patient age was 59 years. The choroidal
melanoma was a mean of 3.6 mm from the optic disc and 2.6 mm from the foveola.
The mean tumour basal dimension was 11 mm and the mean tumour thickness was 4
mm. The choroidal melanoma showed intrinsic hypoautofluorescence (39%),
isoautofluorescence (6%) and hyperautofluorescence (55%). Slightly increased
hyperautofluorescence of the melanoma was found in pigmented tumours (versus
non-pigmented), those with greater thickness and basal dimensions, and those
with overlying disrupted RPE. Related RPE hyperplasia and atrophy showed
hypoautofluorescence, drusen, RPE detachment and subretinal fluid showed slight
hyperautofluorescence, and orange pigment displayed the brightest
hyperautofluorescence. CONCLUSIONS: Choroidal melanoma generally shows slight
intrinsic hyperautofluorescence and the brightness increases with pigmented
tumours, larger tumours, and those associated with disrupted RPE. Overlying
orange pigment shows remarkably bright hyperautofluorescence.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 18441171 [PubMed - in process]

30: Br J Ophthalmol. 2008 May;92(5):609-11. 

To what extent does a lack of refrigeration of generic chloramphenicol eye-drops
used in India decrease their purity and what are the implications for Europe?

Aboshiha J, Weir R, Singh P, Ewings P, Lovering A.

Institute of Ophthalmology, University College London, London, UK.
jonathan.aboshiha@gmail.com

BACKGROUND/AIMS: Thermal degradation of chloramphenicol occurs at a faster rate
when stored in unrefrigerated conditions. This study measures the concentration
of the principal thermal breakdown product of generic chloramphenicol eye-drops
being sold over the counter in chemists in different locations in India.
METHODS: Forty-eight samples of generic chloramphenicol eye-drops were collected
form Delhi and Chennai (Madras) in India. Conditions of storage of
chloramphenicol eye-drops were recorded at the time of purchase. Concentrations
of a hydrolytic degradation product of chloramphenicol were measured using
validated high-pressure liquid chromatography. Results were compared with
accepted UK standards. RESULTS: Significantly higher levels of chloramphenicol
thermal breakdown product were found in collected samples. All samples purchased
were being stored in unrefrigerated conditions in the chemists sampled. Shelf
lives exceeded UK equivalents, varying considerably between manufacturers.
CONCLUSION: Inadequate refrigeration and prolonged shelf lives of
chloramphenicol generics collected from Delhi and Chennai are associated with
very high levels of chloramphenicol thermal breakdown product. These levels
substantially exceed UK quality-assurance standards undermining product
reliability, possibly contributing to the positive selection of resistant
organisms and product toxicity effects. The principals of quality-assurance
breakdown described are particularly relevant to Europe, following recent
deregulation of chloramphenicol eye-drops purchased over the counter.

PMID: 18441170 [PubMed - in process]