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1.  Management of Bowel Obstruction in Patients with Stage IV Cancer: Predictors of Outcome after Surgery 
Annals of surgical oncology  2012;20(3):707-714.
Patients with Stage IV cancer and bowel obstruction (BO) present a complicated management problem. We sought to determine if specific parameters could predict outcome after surgery.
Records of patients with Stage IV cancer and BO treated from 1991–2008 were reviewed. For surgical patients, 30-day morbidity and 90-day mortality were assessed using exact multivariable Logistic regression methods.
Of 198 patients, 132 (66.7%) underwent surgery, 66 medical treatment alone, and demographics were similar. 41 (20.7%) patients were diagnosed with Stage IV cancer and BO synchronously, all treated surgically; the remaining presented metachronously. Medically managed patients were more likely to have received chemotherapy in the 30 days prior to BO [45/66 (68.2%) vs 40/132 (30.3%), p <0.01]. In the surgical group, 30-day morbidity was 35.6%, while 90-day mortality was 42.3%. Median overall survival for synchronous patients was 14.1 months (95 % CI 7.6, 23.2), and 3.7 months (95 % CI 2.5, 5.2) and 3.6 months (95 % CI 1.5, 5.2) for metachronous patients treated surgically and medically, respectively. A multivariate model for 90-day surgical mortality identified low serum albumin, metachronous presentation, and ECOG > 1 as predictors of death (p<0.05). A model for 30-day surgical morbidity yielded low hematocrit as a predictive factor (p<0.05).
This cohort identifies characteristics indicative of morbidity and mortality in Stage IV cancer and BO. Low serum albumin, ECOG > 1, and metachronous presentation predicted for 90-day surgical mortality. These data suggest factors that can be used to frame treatment discussion plans with patients.
PMCID: PMC4784689  PMID: 22990648
bowel obstruction; Stage IV; surgery; complication
2.  Impact of Harness Fit on Suspension Tolerance 
Human factors  2012;54(3):346-357.
This study investigated the effect of body size and shape and harness fit on suspension tolerance time.
Fall victims may develop suspension trauma, a potentially fatal reduction of return blood flow from legs to the heart and brain, after a successfully arrested fall if they are not rescued quickly or the harness does not fit them well.
For this study, 20 men and 17 women with construction experience were suspended from the dorsal D-ring of a full-body fall-arrest harness. Their suspension tolerance time, physical characteristics, and harness fit levels were assessed.
Body characteristics (i.e., weight, stature, upper- and lower-torso depths) were associated with decreased suspension tolerance time (r = −.36 ~ –.45, p ≤ .03). In addition, harness fit affected suspension tolerance time; workers with a torso angle of suspension greater than 35°, a thigh strap angle greater than 50°, or a poorly fitting harness size had shorter suspension tolerance time (mean differences = 14, 11, and 9.8 min, respectively, p ≤ .05).
Body size and harness fit were predictors of suspension tolerance time. Selecting well-fit harnesses and establishing a 9-min rescue plan are suggested to ensure that no more than 5% of workers would experience suspension trauma.
The study provides a basis for harness designers, standards writers, and manufacturers to improve harness configurations and testing requirements for better worker protection against suspension trauma.
PMCID: PMC4681431  PMID: 22768638
3-D scan; body shape; harness fit; suspension; anthropometry; fall arrest; rescue
3.  Frontal linear scleroderma en coup de sabre associated with epileptic seizure 
BMJ Case Reports  2012;2012:bcr2012007837.
Linear scleroderma is a rare variant of localised scleroderma, which is usually seen in childhood and during the adolescent period, and can cause severe functional morbidity as well as cosmetic and psychological problems. Although its ethiopathogenesis is yet obscure, autoimmunity, local ischaemia and injuries, vaccination, irradiation, vitamin K injections, Borrelia burgdorferi and Varicella infections have been incriminated. A 4-year-old girl who had been followed up for about 18 months with diagnosis of epilepsy had a colour discolouration and depression that first appeared 1 year ago and then progressed on her left frontal region. Her CT scan showed a thinning in the frontal bone and depression in the frontal region. These findings are described as ‘en coup de sabre’ a rare form of linear scleroderma localised at the frontal region of the scalp. In this paper, we present clinical and radiological findings of a 4-year-old girl with epileptic seizures that started 1 year before the onset of the lesion of linear scleroderma.
PMCID: PMC4544967  PMID: 23230261
4.  Ocular symptoms secondary to meningeal carcinomatosis in a patient with lung adenocarcinoma: a case report 
BMC Ophthalmology  2012;12:65.
Meningeal carcinomatosis (MC) is a rare complication associated with hematologic and solid tumors. MC develops when malignant cells gain access to the leptomeningeal space, producing several clinical symptoms. Loss of vision and ocular motility deficit are the most frequent ocular symptoms reported. Fundus examination usually appears normal, although optic nerve alterations like optic atrophy or papilledema have been described. MC diagnosis is usually completed by magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Indicated treatment for MC usually involves intrathecal chemotherapy combined with radiotherapy, although survival rate is extremely low.
Case presentation
A 66-year old man with stage IV metastatic lung adenocarcinoma, presented to the Ophthalmology Department with a two-month history of double vision, soft headaches and dizziness episodes. The patient presented a best visual corrected acuity of 0.7 in his right eye and 0.8 in his left eye. Diplopia was corrected with 6-prism diopters base-out prism in right eye. Funduscopy showed a bilateral papilledema, juxtapapillary exudates and splinter hemorrhages. Brain MRI showed a diffuse leptomeningeal enhancement in cortical sulcus. Lumbar puncture was performed and cerebrospinal fluid (CSF) cytology revealed malignant cells compatible with a diagnosis of MC. Intrathecal chemotherapy was administered.
MC is a serious complication of systemic cancer patients, involving a poor prognosis. Early diagnosis is extremely important, although treatment is frequently aimed to reduce the symptoms and extend survival. Eye symptoms may be the chief complaint, so MC should be considered in any patient with vision loss or diplopia accompanied by neurologic symptoms and in the absence of an intraocular cause, especially in the context of systemic cancer.
PMCID: PMC3548754  PMID: 23249254
5.  Spontaneous malignant glaucoma in a patient with patent peripheral iridotomy 
BMC Ophthalmology  2012;12:64.
To report a case of spontaneous malignant glaucoma in an Asian female. To propose the term “positive vitreous pressure glaucoma” to reflect the pathophysiology, treatment and prognosis of the condition.
Case presentation
A 56-year old Chinese female was diagnosed of primary angle closure glaucoma and had bilateral laser peripheral iridotomy one year ago. She presented with spontaneous onset of malignant glaucoma involving the left eye. The condition was treated successfully; the final best corrected visual acuity was 0.67 (decimal notation).
This case highlights that acute angle closure attack can occur in an eye with patent peripheral iridotomy. Early recognition and treatment is essential for good visual prognosis.
PMCID: PMC3554438  PMID: 23241197
6.  Orbital glomus tumor in an Asian patient 
BMC Ophthalmology  2012;12:62.
This report describes a recurrent orbital glomus tumor in an Asian patient.
Case presentation
A healthy 50-year-old Korean man had progressive right exophthalmos and a soft mass on his right lower lid for 6 months. We evaluated the mass using CT and MRI, and performed excisional biopsy and pathologic examination. Pathologically, the mass was a glomus tumor. Although proptosis of the right eye decreased, one month after surgery it increased to almost the same level as before surgery.
This is the first report of an Asian patient with an orbital glomus tumor that demonstrated rapid re-growth after incision without pain or visual problems.
PMCID: PMC3536637  PMID: 23216695
Orbital glomus tumor; Asian patients; Recur; Rapid growth; Painless
7.  Increased expression of oxyproteins in the optic nerve head of an in vivo model of optic nerve ischemia 
BMC Ophthalmology  2012;12:63.
To investigate the effects of microvascular compromise on the expression of oxidative proteins in the optic nerve head.
Endothelin-1 (0.1 μg/day) was delivered to the perineural region of the anterior optic nerve by osmotically driven minipumps for two, four, and eight weeks in ten rabbits, respectively. As a control, a balanced salt solution was delivered for two and eight weeks in five rabbits, respectively. Expression of oxyproteins in the cornea, vitreous, retina, and optic nerve head for each time period was determined using the OxyBlot protein oxidation detection kit. Retina was stained with H&E and TUNEL for histological examination.
There was a significant increase in the expression of oxyproteins in the optic nerve head after two weeks of endothelin-1 administration (p < 0.001, Mann Whitney U test). In contrast, there was no expression of oxyproteins in the cornea, retina, or vitreous. The number of cells in the retinal ganglion cell layer, inner nuclear layer, and outer nuclear layer decreased remarkably with time in the endothelin-1-treated group. Furthermore, the inner and outer nuclear layers, as well as the inner and outer plexiform layers, became thinner over time.
Administration of endothelin-1 to the microvasculature of the optic nerve leads to increased expression of oxyproteins in the optic nerve head and loss of retinal ganglion cells.
PMCID: PMC3541215  PMID: 23216747
Ischemia; Optic nerve; Oxyproteins; Oxyblot
8.  Intraocular pressure in a cohort of healthy eastern European schoolchildren: variations in method and corneal thickness 
BMC Ophthalmology  2012;12:61.
Intraocular pressure (IOP) in the developing eye of a child is not always easy to measure and there is no technique that is known to be the most accurate for the young eye. Measurements are needed on many cohorts of children with different tonometers to determine how the values correlate between instruments, whether corneal parameters affect readings and whether correlations between age and IOP values can be discerned. The aim of this study was to undertake a comparative analysis of three different tonometers on a group of healthy children to see whether differences exist and whether these may be related to central corneal thickness and/or radius of curvature. In addition, the study adds to the relatively small body of literature on IOP in the growing eye which will collectively allow trends to be identified and ultimately norms to be established.
IOP was measured on 115 eyes in a group of Polish children, aged between 5–17 years (mean ± standard deviation [SD] 11.3 ± 3.0 years) using three different tonometers: non-contact (NCT), the ICare and Goldmann applanation (GAT). Readings obtained were compared between instruments and with central corneal thickness and radius of curvature.
The ICare tonometer provided statistically higher IOP values (16.9 ± 3.4 mmHg) than the GAT (14.7 ± 2.9 mmHg) regardless of corneal thickness and whether or not a correction factor was applied. A correlation was found between central corneal thickness (CCT) and IOP values obtained with all three tonometers but only the IOP values detected with the ICare tonometer showed a statistically significant correlation with radius of curvature (p < 0.004). No correlations with age or gender were found for IOP values measured with any of the instruments.
IOP measurements on children vary significantly between instruments and correlations are affected by the corneal thickness. Further studies on children are needed to determine which instrument is most appropriate and to derive a normative IOP scale for the growing eye.
PMCID: PMC3526441  PMID: 23199262
Cornea; Child; Paediatric Ophthalmology; Intraocular pressure; Tonometry
9.  Immunohistochemical localization of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and α2-antiplasmin in human corneal perforation: a case report 
BMC Ophthalmology  2012;12:60.
Corneal ulceration leading to perforation is associated with infectious and non-infectious destructive conditions in the cornea. The fibrinolytic (plasminogen/plasmin) system is considered to contribute to tissue remodeling in the wound healing process and it is believed to play an important role in proteolysis and fibrosis. To determine the localization of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR) and α2-antiplasmin (α2AP) in the tissue of a corneal perforation, we investigated immunohistochemical expressions of u-PA, u-PAR, α2AP, CD68, and α-smooth muscle actin (α-SMA) in a patient with corneal perforation that developed from an ulcer of no clear cause.
Case presentation
The patient was a 77-year-old woman who presented with a perforated corneal ulcer in her right eye. The cause of her corneal ulcer was unknown. Double immunohistochemistry was performed for the combinations of u-PA with u-PAR, CD68 or α-SMA and α2AP with CD68 or α-SMA to detect the localization of u-PA and α2AP. u-PA and u-PAR co-localization was seen in the corneal ulceration area. u-PA was mainly observed in CD68-positive cells and in some α-SMA positive cells. On the other hand, α2AP was not expressed in CD68-positive cells, but was expressed in α-SMA positive cells.
We identified expression of the u-PA/u-PAR complex and α2AP in a patient with a corneal ulcer. These two molecules are believed to play a crucial role in inflammatory cell recruitment, ECM synthesis and degradation during corneal wound healing.
PMCID: PMC3534481  PMID: 23190581
u-PA; u-PAR; Corneal wound healing; α2-antiplasmin; Corneal perforation
10.  The impact of central corneal thickness on intraocular pressure among Ethiopian glaucoma patients: a cross-sectional study 
BMC Ophthalmology  2012;12:58.
Raised intraocular pressure (IOP) is the only causal risk factor for glaucoma that can be therapeutically manipulated to change the course of the disease process. Though Goldman applanation tonometry (GAT) is the “gold standard” for IOP measurement, readings of IOP with GAT are affected by central corneal thickness (CCT). The aim of this study is to determine the impact of CCT on IOP among Ethiopian glaucoma patients.
It was a multicenter cross-sectional study and all glaucoma patients visiting their respective eye clinic during the study period were included. A total of 199 randomly selected glaucomatous eyes from 199 patients aged 18 years and above were employed. The CCT was measured by OcuScan™ RxP Ophthalmic Ultrasound and IOP was measured with Goldmann applanation tonometer. Linear regression and bivariate correlation analysis were carried out and level of significance was taken at 5%.
The mean IOP was 19.46(±7.05) mmHg and mean CCT was 508.07(±33.26) μm. The mean IOP for primary open angle glaucoma (POAG), ocular hypertension (OHT), normal tension glaucoma (NTG), pseudoexfoliative glaucoma (PXG) and primary chronic angle closure glaucoma (PCAG) patients was 19.22 mmHg, 21.39 mmHg, 14.33 mmHg, 33.25 mmHg and 14.75 mmHg respectively. The mean CCT values were 502.24 μm (POAG), 524.32 μm (OHT), 500.75 μm (NTG), 579.00 μm (PXG) and 530.25 μm (PCAG). Age of the patient and glaucoma surgery had an influence on corneal thickness. A positive relationship was found between CCT and IOP (p < 0.001).
The mean CCT of Ethiopian glaucoma patients is thin in comparison to other ethnic groups and patients with OHT have thicker corneas than POAG patients. Hence determination of CCT for each patient is necessary in the up-to-date glaucoma management.
PMCID: PMC3534335  PMID: 23181800
Intraocular pressure; Central corneal thickness; Glaucoma; Pachymeter
11.  Association analysis of cigarette smoking with onset of primary open-angle glaucoma and glaucoma-related biometric parameters 
BMC Ophthalmology  2012;12:59.
To date, studies on the role played by cigarette smoking in primary open-angle glaucoma (POAG) remains controversial. The current study evaluated cigarette smoking as a risk factor of POAG and its relationships with vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT) and intraocular pressure (IOP) in a Chinese cohort.
In a total of 248 unrelated individuals including 30 juvenile-onset POAG (JOAG), 92 adult-onset POAG (AOAG) and 126 sex-matched senile cataract controls, underwent comprehensive ophthalmic examination. Their smoking was obtained and documented by questionnaire. Association of cigarette smoking with POAG was performed using logistic regression controlled for age and sex. Effects of cigarette smoking on VCDR, IOP and CCT were analyzed with multiple linear regression.
In either JOAG or AOAG, no association of cigarette smoking was found with disease onset (P = 0.692 and 0.925 respectively). In controls and JOAG, no significant effects of smoking were found on VCDR, IOP or CCT (all P > 0.05). Smoking was found to be correlated with decreased CCT in AOAG and combined POAG (JOAG + AOAG) (P = 0.009 and 0.003), but no association with VCDR or IOP was observed (P > 0.05).
Although cigarette smoking was not found to be risk factor for onset of POAG, it was correlated with CCT in AOAG, and thus might still play a role in the disease course, especially for AOAG.
PMCID: PMC3549870  PMID: 23186177
Primary open angle glaucoma; Cigarette smoking; Central corneal thickness; Vertical cup-to-disc ratio; Intraocular pressure
12.  Protocol for a randomised controlled trial to estimate the effects and costs of a patient centred educational intervention in glaucoma management 
BMC Ophthalmology  2012;12:57.
Poor glaucoma education is thought to be a causative factor of non-adherence to glaucoma therapy. However, the multi-factorial nature of non-adherent behaviour may explain the failure of purely educational interventions to achieve significant improvement in adherence. Behaviour Change Counselling (BCC) allows both the imparting of information and assessment of patient ambivalence to medication use and may elicit behaviour change in order to achieve better adherence. The chronic and complex nature of glaucoma means that patient non-adherence to glaucoma therapy does not easily correlate with measureable objective clinical endpoints. However, electronic medication monitoring offers an objective method of measuring adherence without reliance on clinical endpoints.
The study is a randomised controlled trial (RCT) with glaucoma (open angle) or ocular hypertension patients attending a glaucoma clinic and prescribed travoprost. The study will determine whether additional glaucoma education using BCC is beneficial and cost effective in improving adherence with glaucoma therapy. An 8-month follow-up period, using an electronic adherence monitoring device (Travalert® dosing aid, TDA), will indicate if the intervention is likely to be sustained in the longer term. Additionally, a cost-effectiveness framework will be used to estimate the cost benefit of improving adherence. The development of a novel intervention to deliver glaucoma education using BCC required practitioner training and fidelity testing. Five practitioners were successfully trained to become Glaucoma Support Assistants able to deliver the BCC intervention. The research group had prior clinical and investigative experience in this setting, and used multiple strategies to design a method to address the study objectives.
This RCT, using BCC to improve adherence to ocular hypotensive therapy, to our knowledge is the first within this disease area. Using a variety of adherence measures allows examination of the known inaccuracies of patient self-report with respect to glaucoma medication. The novel BCC component has undergone fidelity testing using BECCI and the BCC template will ensure conformity to a standardised intervention.
Trial registration
Current Controlled Trials: ISRCTN89683704
PMCID: PMC3536708  PMID: 23171166
Adherence; Compliance; Glaucoma; Ocular hypotension medication; Motivational interviewing; Behaviour change counselling; Travalert® dosing aid
13.  Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy 
BMC Ophthalmology  2012;12:56.
Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy.
Case presentation
We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive) with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive) in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively degenerated and replaced with empty vacuoles and disintegrated organelles.
This case provides a convincing histological evidence of melanoma-associated autoantibodies directly against transient receptor potential M1 channels that target the ON bipolar cell structures in the inner nuclear and outer plexiform layers in paraneoplastic vitelliform retinopathy.
PMCID: PMC3514129  PMID: 23148706
Paraneoplastic vitelliform retinopathy; Autoimmune retinopathy; Transient receptor potential channel; Bipolar cell; Melanoma-associated retinopathy; Autoantibody
14.  Knowledge of patients’ visual experience during cataract surgery: a survey of eye doctors in Karachi, Pakistan 
BMC Ophthalmology  2012;12:55.
Several recent studies have recommended that ophthalmologists must be aware of the visual sensations (and their associated anxiety/fear) experienced by patients undergoing cataract surgery. We assessed the knowledge of a group of eye doctors in Pakistan regarding these phenomena.
This was a cross-sectional survey. Eye doctors (ophthalmologists, residents and medical officers) attending the Ophthalmological Society of Pakistan Annual Conference 2011, in Karachi were invited to participate in the study. A self-administered structured questionnaire was used to examine their knowledge of visual sensations and their associated anxiety/fear experienced by patients during cataract surgery. Simple frequencies and proportions were calculated to describe the data.
A total of 150 ophthalmologists, residents and medical officers were invited to participate in the study. Of these, 68 (45.3%) responded. The mean age (±SD) of the participants was 42.9 (13.2) years. The proportion of participants who thought that patients could experience visual sensations during cataract surgery under regional anaesthesia was 89.7% and that under topical anaesthesia was 73.5%. The most frequently cited sensations included: light perception, changes in light brightness, movements, instruments and surgeon’s hands or fingers.
The eye doctors estimated that 38.9% and 64.3% patients would see at least something during cataract surgery under regional anaesthesia and topical anaesthesia, respectively. They also believed that 24.2%-36.9% of patients may experience anxiety/fear as a result of visual sensations during such surgery. Approximately half of the eye doctors did not think that retained vision was a source of fear or anxiety for the patients. While most of them acknowledged the importance of preoperative counselling in helping to alleviate such fear/anxiety, the majority of them did not regularly counsel their patients on what to expect during the surgery.
Our study reveals that a significant proportion of eye doctors do not have adequate knowledge of the visual phenomenon and their associated anxiety or fear, that patients can experience during cataract surgery. Targeted educational interventions are needed to increase awareness of this phenomenon among eye care professionals.
PMCID: PMC3544590  PMID: 23137054
15.  Perimetric and retinal nerve fiber layer findings in patients with Parkinson’s disease 
BMC Ophthalmology  2012;12:54.
Visual dysfunction is common in Parkinson’s disease (PD). It remains, however, unknown whether it is related to structural alterations of the retina. The aim of this study is to compare visual field (VF) findings and circumpapillary retinal nerve fiber layer (RNFL) thickness in a series of PD patients and normal controls, in order to assess possible retinal anatomical changes and/or functional damage associated with PD.
PD patients and controls were recruited and underwent VF testing with static automated perimetry and RNFL examination with optical coherence tomography (OCT). Cognitive performance using Mini Mental State Examination (MMSE), PD staging using modified Hoehn and Yahr (H-Y) scale and duration of the disease was recorded in PD patients.
One randomly selected eye from each of 24 patients and 24 age-matched controls was included. OCT RNFL thickness analysis revealed no difference in the inferior, superior, nasal or temporal sectors between the groups. The average peripapillary RNFL was also similar in the two groups. However, perimetric indices of generalized sensitivity loss (mean deviation) and localized scotomas (pattern standard deviation) were worse in patients with PD compared to controls (p < 0.01). 73% of eyes of PD patients had glaucomatous-like asymmetrical hemifield defects with abnormal Glaucoma Hemifield Test and various combinations of arcuate defects (n = 12), nasal steps (n = 11) and paracentral scotomas (n = 16). Bilateral defects were found in 14 patients (58%). No correlation was found between VF indices and MMSE or H-Y scores.
PD patients may demonstrate glaucomatous-like perimetric defects even in the absence of decreased RNFL thickness.
PMCID: PMC3515471  PMID: 23031247
Visual loss; Visual fields; Parkinson's disease; Retina; Visual processing
16.  Changes in intraocular pressure after pharmacologic pupil dilation 
BMC Ophthalmology  2012;12:53.
Intraocular pressure (IOP) may vary according to the change of ocular conditions. In this study, we want to assess the effect and mechanism of pupil dilation on IOP in normal subjects.
We prospectively evaluated 32 eyes of 32 patients (age; 61.7 ± 8.2 years) with normal open angles under diurnal IOP. IOP was measured every two hours from 9 AM to 11 PM for one day to establish baseline values and was measured again for one day to assess the differences after dilation. To induce dilation, we administered 2.5% phenylephrine and 1% tropicamide every 5 minutes from 8:30 AM to 8:45 AM and for every two hours from 11 AM to 9 PM to keep the pupil dilated. Diurnal IOP, biometry, Visante OCT, and laser flare photometry were measured before and after dilation.
We observed a significant increase in IOP after dilation, 1.85 ± 2.01 mmHg (p = 0.002). IOP elevation remained significant until about four hours after dilation. Thereafter, IOP decreased slowly and eventually reached pre-dilation level (p > 0.05). Flare values decreased, and the anterior chamber angle became wider after mydriasis.
Dilation of the pupil significantly and incidentally elevated IOP in normal subjects. Further related studies are warranted to characterize the mechanism of the increased IOP after dilation.
PMCID: PMC3499138  PMID: 23017184
Mydriasis; Flare; Anterior chamber angle; IOP variation
17.  Goldmann applanation tonometry compared with corneal-compensated intraocular pressure in the evaluation of primary open-angle Glaucoma 
BMC Ophthalmology  2012;12:52.
To better understand the role of corneal properties and intraocular pressure (IOP) in the evaluation of primary open-angle glaucoma (POAG); and to determine the feasibility of identifying glaucomatous optic neuropathy (GON) using IOP corrected and uncorrected for corneal biomechanics.
Records from 1,875 eyes of consecutively evaluated new patients were reviewed. Eyes were excluded if central corneal thickness (CCT) or Ocular Response Analyzer (ORA) measurements were unavailable. Presence or absence of GON was determined based on morphology of the optic disc, rim and retinal nerve fiber layer at the time of clinical examination, fundus photography and Heidelberg Retinal Tomography. Goldmann-applanation tonometry (GAT) in the untreated state was recorded and Goldmann-correlated (IOPg) and corneal-compensated IOP (IOPcc) were obtained using the ORA. Glaucomatous eyes were classified as normal or high-tension (NTG, HTG) using the conventional cutoff of 21 mm Hg. One eligible eye was randomly selected from each patient for inclusion.
A total of 357 normal, 155 HTG and 102 NTG eyes were included. Among NTG eyes, IOPcc was greater than GAT (19.8 and 14.4 mm Hg; p < 0.001) and the difference between IOPcc and GAT was greatest for this subgroup of patients with NTG (p ≤ 0.01). The maximum combined sensitivity and specificity for detection of GON occurred at 20.9 mm Hg for GAT (59%, 90%) and 18.4 mm Hg for IOPcc (85%, 85%) and the area under the curve was greater for IOPcc (0.93 vs. 0.78; p < 0.001).
IOPcc may account for measurement error induced by corneal biomechanics. Compared to GAT, IOPcc may be a superior test in the evaluation of glaucoma but is unlikely to represent an effective diagnostic test.
PMCID: PMC3514140  PMID: 23009074
Open-angle glaucoma; Low tension glaucoma; Intraocular pressure; Intraocular pressure; Ocular tonometry
18.  Access to eye health services among indigenous Australians: an area level analysis 
BMC Ophthalmology  2012;12:51.
This project is a community-level study of equity of access to eye health services for Indigenous Australians.
The project used data on eye health services from multiple sources including Medicare Australia, inpatient and outpatient data and the National Indigenous Eye Health Survey.
The analysis focused on the extent to which access to eye health services varied at an area level according to the proportion of the population that was Indigenous (very low = 0-1.0%, low = 1.1-3.0%, low medium = 3.1-6.0%, high medium = 6.1-10.0%, high = 10.1-20.0%, very high = 20 + %). The analysis of health service utilisation also took into account age, remoteness and the Socioeconomic Indices for Areas (SEIFA).
The rate of eye exams provided in areas with very high Indigenous populations was two-thirds of the rate of eye exams for areas with very low indigenous populations. The cataract surgery rates in areas with high medium to very high Indigenous populations were less than half that reference areas. In over a third of communities with very high Indigenous populations the cataract surgery rate fell below the World Health Organization (WHO) guidelines compared to a cataract surgery rate of 3% in areas with very low Indigenous populations.
There remain serious disparities in access to eye health service in areas with high Indigenous populations. Addressing disparities requires a co-ordinated approach to improving Indigenous people’s access to eye health services. More extensive take-up of existing Medicare provisions is an important step in this process. Along with improving access to health services, community education concerning the importance of eye health and the effectiveness of treatment might reduce reluctance to seek help.
PMCID: PMC3514169  PMID: 22998612
Aboriginal and Torres Strait Islander; Indigenous; Eye; Cataract; Equity
19.  The distribution of axial length, anterior chamber depth, lens thickness, and vitreous chamber depth in an adult population of Shahroud, Iran 
BMC Ophthalmology  2012;12:50.
Ocular biometric parameters can be influenced by race, ethnicity, and genetics; their differences across different populations can probably explain differences in refractive errors in these populations. The aim of this study is to determine the normal range of axial length, anterior chamber depth, lens thickness, and vitreous chamber depth in the population of Shahroud in the north of Iran.
In the first phase of Shahroud Eye Cohort Study, the 40–64 year old population were sampled cross-sectionally; 6311 were invited and 5190 (82.2%) participated in the study. Biometric examinations were done using the LENSTAR/BioGraph (WaveLight AG, Erlangen, Germany) after vision tests and before cycloplegic refraction tests. Any type of eye surgery, extensive pterygium, and lack of cooperation were used as exclusion criteria, and analyses were done with data from 4869 eyes.
We found a mean axial length of 23.14 mm (95% confidence interval [CI], 23.11-23.17), mean anterior chamber depth of 2.62 mm (95% CI, 2.60-2.63), mean lens thickness of 4.28 mm (95% CI, 4.27-4.29), and the mean vitreous chamber depth was 15.72 mm (95% CI, 15.70-15.75).
Kolmogorov-Smirnov tests showed that the distribution of axial length, anterior chamber depth, lens thickness, and vitreous chamber depth significantly differed from normal; axial length and vitreous chamber depth demonstrated a leptokurtic distribution as well.
Axial length, anterior chamber depth, and vitreous chamber depth significantly decreased with age, and lens thickness significantly increased with age (p < 0.001). All indices were significantly higher in men.
The distributions of axial length, vitreous chamber depth, and lens thickness are reported for the first time in an Iranian adult population. Compared to other studies, axial length was in the mid range, nonetheless, studying axial length components showed that the Iranian population had smaller anterior chamber depth and lens thickness. Age and gender were significantly associated with all indices assessed in this study.
PMCID: PMC3500253  PMID: 22988958
Axial length- Anterior chamber depth lens thickness- Vitreous chamber depth; Normal range
20.  Role of Heat Shock Protein 47 in Transdifferentiation of Human Tenon's Fibroblasts to Myofibroblasts 
BMC Ophthalmology  2012;12:49.
Heat shock protein 47 (Hsp47) is a well-known molecular chaperone in collagen synthesis and maturation. The aim of this study is to investigate its putative role in the transdifferentiation of Tenon’s fibroblasts to myofibroblasts.
Primary cultured human Tenon’s fibroblasts were exposed to transforming growth factor-β1 (TGF-β1) for up to 48 hours. The mRNA levels of Hsp47 and α smooth muscle actin (αSMA) were determined by quantitative real time RT-PCR. After delivery of small interfering RNA (siRNA) molecules targeting Hsp47 into the cells, the expression of Hsp47 and αSMA proteins was determined by western immunoblotting.
TGF-β1 increased the mRNA expressions of both Hsp47 and αSMA in human Tenon’s fibroblasts, as determined by quantitative real time RT-PCR. However, it induced the protein expression of only αSMA but not Hsp47, as determined by western immunoblots. When siRNAs specific for Hsp47 were introduced into those cells, the TGF-β1-induced expression of αSMA was significantly attenuated on western immunoblots; after 48 hours of exposure to TGF-β1, the relative densities of immunobands were 11.58 for the TGF-β1 only group and 2.75 for the siRNA treatment group, compared with the no treatment control group (p < 0.001).
Our data suggest that Hsp47 may be related to the TGF-β1-induced transdifferentiation of human Tenon’s fibroblasts to myofibroblasts.
PMCID: PMC3490793  PMID: 22967132
Fibroblast; Fibrosis; Heat shock protein; Myofibroblast; Transforming growth factor-β
21.  Valacyclovir in the treatment of acute retinal necrosis 
BMC Ophthalmology  2012;12:48.
To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN).
This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease.
Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks).
Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.
PMCID: PMC3487766  PMID: 22947428
Acute retinal necrosis; Herpetic retinitis; Acyclovir; Valacyclovir
22.  Gold Bead Implantation in Acupoints for Coxofemoral Arthrosis in Dogs: Method Description and Adverse Effects 
Simple Summary
Traditional acupuncture uses needles inserted at certain acupuncture points. Gold bead implantation at acupuncture points is used in acupuncture intended to relieve pain in certain diseases. The method of gold implantation is not well described in the literature. We describe the technique of implanting 24-karat gold beads around the joints of dogs with degenerative joint disease due to chronic hip dysplasia. The method is safe and fairly easy to perform under anesthesia. It has few serious side effects, as long as bead-deposition within the joint is avoided. There is some aggravation of discomfort during the first two weeks after treatment as well as bleeding and synovial leakage during treatment.
Gold bead implantation has been used for years as an alternative method to improve function in chronic joint disease both in humans and dogs. The aims of the present study were to describe the technique of implanting 24-karat gold beads around the hip joints of dogs with chronic hip dysplasia, and to record any side effects or complications of such treatment. A prospective placebo-controlled double-blinded clinical trial was performed. Eighty dogs were randomly allocated to treatment or placebo, with 38 in the gold implantation group and 42 in the placebo group, and followed intensely for six months. The implantation technique was simple to perform, using fluoroscopy and with the dogs under inhalation anesthesia for about 30 minutes. Adverse effects, measured as pain or discomfort, were seen for a period of up to four weeks in 15 of the dogs in the gold implantation group, compared to six dogs in the placebo group. During implantation, a technical difficulty occurred as 82% of the dogs showed leakage of blood and/or synovia from the needles. The dogs in the gold implantation group were radiographed 18 months later. Of the 30 dogs that were radiographed at both inclusion and 24 months, 80% (24 dogs) showed a deterioration of the coxofemoral arthrosis, the other six had stable disease evaluated by radiography. Migration of gold beads was only observed in one dog.
PMCID: PMC4494288  PMID: 26487031
acupuncture; side effects; canine; gold wire; degenerative joint disease; hip dysplasia; pain treatment
23.  Severe conjunctivochalasis in association with classic type Ehlers-Danlos syndrome 
BMC Ophthalmology  2012;12:47.
Inferior conjunctivochalasis is common, but is rarely severe enough to require conjunctival excision. This report describes a patient with severe conjunctivochalasis who was subsequently diagnosed with Ehlers Danlos Syndrome, Classic Type.
Case presentation
A patient suffering from foreign body sensation, frequent blinking and bilateral inferior conjunctivochalasis was referred and treated by topical ocular lubrication. However, no improvement was observed prompting potential excision of conjunctivochalasis. Following patient consultation and clinical diagnosis including hypermobile joints and skin elasticity, poor wound healing and wide scar morphology, Ehlers-Danlos syndrome was confirmed in the patient.
This case highlights the need for direct patient questioning and provides the first reported association between conjunctiovochalasis and Ehlers-Danlos syndrome.
PMCID: PMC3504533  PMID: 22943506
Conjunctivochalasis; Ehlers-Danlos syndrome; Kyphoscoliosis
24.  The case for intraocular delivery of PPAR agonists in the treatment of diabetic retinopathy 
BMC Ophthalmology  2012;12:46.
Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular agents. In addition, we introduce the peroxisome proliferator-activated receptors and describe their functions in response to the drugs.
Based on the evidence of large-scale clinical studies investigating the systemic administration of fenofibrate, this ligand for peroxisome proliferator-activated receptor-α is potentially a good candidate for intraocular delivery. Here, we describe the mechanisms by which it might be acting to improve diabetic retinopathy, its relative safety and we speculate on how it could be developed for intraocular delivery.
In this paper, we provide a rationale for the further investigation of peroxisome proliferator-activated receptor-α agonists as intraocular agents for the treatment of diabetic retinopathy.
PMCID: PMC3532122  PMID: 22937835
Diabetes; Diabetic retinopathy; Intraocular; Fenofibrate; TZDs; PPARs
25.  Recurrent orbital schwannomas: clinical course and histopathologic correlation 
BMC Ophthalmology  2012;12:44.
Schwannomas are slow-growing typically encapsulated tumors composed of differentiated Schwann cells, the primary class of peripheral glial cells. Complete excision is the treatment of choice for orbital schwannomas that cause pain, disfigurement, diplopia, or optic neuropathy. The presence of multiple schwannomas in a single patient suggests possible association with neurofibromatosis type 2 (NF2) or schwannomatosis.
Case presentation
We present 2 patients who experienced recurrent orbital schwannoma without evidence for neurofibromatosis. The recurrence in one patient, a 59-year old man, occurred 6 years after complete excision of the initial tumor. This recurrence consisted of 2 independent tumors in the same orbit. The recurrence in the second patient, a 5 year-old girl, occurred multiple times within days to weeks of partial excisions until eventually a complete excision was performed.
The clinical history, histopathologic features and particularly the intraoperative findings suggest that the 59 year old man suffers from orbital schwannomatosis, while the rapid recurrence in the second patient correlated with the cellular features of her plexiform schwannoma. Hence, the recurrence in each patient is linked to a different etiology, with implications for treatment and patient counseling given the difficulty in treating orbital schwannomatosis. To our knowledge, this is the first description of isolated orbital schwannomatosis.
PMCID: PMC3503695  PMID: 22937797

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