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1.  The Impact of Multiple Malignancies on Patients with Bladder Carcinoma: A Population-Based Study Using the SEER Database 
Advances in Urology  2009;2009:406965.
Purpose. To date, no study has examined a population-based registry to determine the impact of multiple malignancies on survival of bladder cancer patients. Our experience suggests that bladder cancer patients with multiple malignancies may have relatively positive outcomes. Materials & Methods. We utilized data from the Surveillance Epidemiology and End Results (SEERs) database to examine survival between patients with only bladder cancer (BO) and with bladder cancer and additional cancer(s) antecedent (AB), subsequent (BS), or antecedent and subsequent to bladder cancer (ABS). Results. Analyses demonstrated diminished survival among AB and ABS cohorts. However, when cohorts were substratified by stage, patients in the high-stage BS cohort appeared to have a survival advantage over high-stage BO patients. Conclusions. Bladder cancer patients with multiple malignancies have diminished survival. The survival advantage of high-stage BS patients is likely a statistical phenomenon. Such findings are important to shape future research and to improve our understanding of patients with multiple malignancies.
PMCID: PMC2801451  PMID: 20069054
2.  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
3.  Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema 
To determine the relationship between retinal ischaemia and the presence of macular oedema (DMO) in patients with diabetic retinopathy (DR) using ultra-widefield fluorescein angiography (UWFA) imaging.
A retrospective review of 122 eyes of 70 treatment-naïve diabetic patients who underwent diagnostic UWFA using the Optos 200Tx imaging system. Two independent, masked graders quantified the area of retinal ischaemia. Based on clinical examination and optical coherence tomography (OCT), each patient was given a binary classification as either having DMO or no DMO. McNemar's test (with Yates' correction as indicated) and a two-sample test of proportions were used to determine the relationship between DMO and ischaemia for binary and proportional data, respectively. Linear and logistic models were constructed using generalised estimating equations to test relationships between independent variables, covariates and outcomes while controlling for inter-eye correlation, age, gender, haemoglobin A1c, mean arterial pressure and dependence on insulin.
Seventy-six eyes (62%) exhibited areas of retinal ischaemia. There was a significant direct correlation between DMO and peripheral retinal ischaemia as seen on UWFA (p<0.001). In addition, patients with retinal ischaemia had 3.75 times increased odds of having DMO compared with those without retinal ischaemia (CI 1.26 to 11.13, p<0.02).
Retinal ischaemia is significantly correlated with DMO in treatment-naïve patients with DR. UWFA is a useful tool for detecting peripheral retinal ischaemia, which may have direct implications in the diagnosis, follow-up and treatment such as targeted peripheral photocoagulation.
PMCID: PMC3329634  PMID: 22423055
Ultra-wide field imaging; fluorescein angiography; diabetes; diabetic retinopathy; diabetic macular oedema; retina; epidemiology; retina
4.  The relationship between corneal hysteresis and the magnitude of intraocular pressure reduction with topical prostaglandin therapy 
To evaluate corneal hysteresis (CH) and intraocular pressure (IOP) before and after IOP lowering with prostaglandin analogue (PGA) therapy in medication-naïve eyes.
In this retrospective study, we included records from 57 consecutive patients with open angle glaucoma who were initiated on PGA. Patients underwent ocular response analyser measurement with IOP assessment at baseline (untreated) and at follow-up (treated).
Median follow-up time between IOP measurements was 1.4 (range 0.4–13.5) months. IOP was reduced by 3.2 mm Hg (18.8%) from 17.0 to 13.8 mm Hg (p<0.001). CH increased by 0.5 mm Hg (5.2%) from 9.7 to 10.2 mm Hg (p=0.02). Baseline CH (but not baseline central corneal thickness) was a significant predictor of the magnitude of IOP reduction, with patients in the lowest quartile of CH (mean 7.0 mm Hg) experiencing a 29.0% reduction in IOP while those in the highest CH quartile (mean 11.9 mm Hg) experienced a 7.6% reduction in IOP (p=0.006). A multivariate analysis controlling for baseline IOP demonstrated that baseline CH independently predicted the magnitude of IOP reduction with PGA therapy in both per cent (ß=3.5, p=0.01) and absolute (ß=0.6, p=0.02) terms.
Although CH is influenced by IOP, baseline CH is independently associated with the magnitude of IOP reduction with PGA therapy.
PMCID: PMC3261726  PMID: 21436180
Corneal hysteresis; ocular response analyser; corneal thickness; glaucoma; prostaglandin analogue; intraocular pressure; diagnostic tests/investigation; treatment medical
5.  Detection of retinal changes in Parkinson’s disease with spectral-domain optical coherence tomography 
This pilot study investigated whether high-resolution spectral-domain optical coherence tomography (SD-OCT) could detect differences in inner retinal layer (IRL), peripapillary retinal nerve fiber layer (RNFL), and macular thickness between patients with Parkinson’s disease (PD) and controls.
Both eyes of patients with PD and age-matched controls were imaged with the Heidelberg Spectralis® HRA + OCT. RNFL, IRL, and macular thickness were measured for each eye using Heidelberg software. These measurements were compared with validated, published normal values for macular and RNFL thickness, and compared with matched controls for IRL thickness.
Eighteen eyes from nine subjects with PD and 19 eyes of 16 control subjects were evaluated using SD-OCT. The average age of PD patients was 64 years with a range of 52–75 years. The average age of controls was 67 years with a range of 50–81 years. No significant reduction in IRL thickness was detected between PD patients and age-matched controls at 13 points along a 6 mm horizontal section through the fovea. No significant difference in RNFL thickness was detected between PD patients and published normal values. Overall average RNFL thickness was 97 μm for PD patients, which exactly matched the normative database value. However, significant differences in macular thickness were detected in three of nine subfields between PD subjects and published normal values. In PD subjects, the outer superior subfield was 2.8% thinner (P = 0.026), while the outer nasal and inner inferior subfields were 2.8% (P = 0.016) and 2.7% (P = 0.001) thicker compared to published normal values.
In this pilot study, significant differences in macular thickness were detected in three of nine subfields by SD-OCT. However, SD-OCT did not detect significant reductions in peripapillary RNFL and IRL thickness between PD patients and controls. This suggests that macular thickness measurements by SD-OCT may potentially be used as an objective, noninvasive, and easily quantifiable in vivo biomarker in PD. Larger, longitudinal studies are needed to explore these relationships further.
PMCID: PMC3000768  PMID: 21188154
Parkinson’s disease; spectral-domain optical coherence tomography; nerve fiber layer thickness; macular thickness; inner retinal layer thickness
6.  Retinal nerve fiber layer evaluation in multiple sclerosis with spectral domain optical coherence tomography 
Histopathologic studies have reported retinal nerve fiber layer (RNFL) thinning in various neurodegenerative diseases. Attempts to quantify this loss in vivo have relied on time-domain optical coherence tomography (TDOCT), which has low resolution and requires substantial interpolation of data for volume measurements. We hypothesized that the significantly higher resolution of spectral-domain optical coherence tomography (SDOCT) would better detect RNFL changes in patients with multiple sclerosis, and that RNFL thickness differences between eyes with and without optic neuritis might be identified more accurately.
In this retrospective case series, patients with multiple sclerosis were recruited from the Judith Jaffe Multiple Sclerosis Center at Weill Cornell Medical College in New York. Patients with a recent clinical diagnosis of optic neuritis (less than three months) were excluded. Eyes with a history of glaucoma, optic neuropathy (other than multiple sclerosis-related optic neuritis), age-related macular degeneration, or other relevant retinal and/or optic nerve disease were excluded. Both eyes of each patient were imaged with the Heidelberg Spectralis® HRA + OCT. RNFL and macular thickness were measured for each eye using the Heidelberg OCT software. These measurements were compared with validated published normal values, and were modeled as linear functions of duration of disease. The odds of an optic neuritis diagnosis as a function of RNFL and macular thickness were calculated.
Ninety-four eyes were prospectively evaluated using OCT. Ages of patients ranged from 26 to 69 years, with an average age of 39 years. Peripapillary RNFL thinning was demonstrated in multiple sclerosis patients; mean RNFL thickness was 88.5 μm for individuals with multiple sclerosis compared with a reported normal value of 97 μm (P < 0.001). Eyes with a history of optic neuritis had more thinning compared with those without optic neuritis (83.0 μm versus 90.5 μm, respectively, P = 0.02). No significant differences were observed in macular thickness measurements between eyes with and without optic neuritis, nor were macular thickness measurements significantly different from normal values. As a function of multiple sclerosis duration and controlling for age, RNFL thickness was decreased in patients with a duration of multiple sclerosis greater than five years compared with those with a duration less than or equal to one year (P = 0.008).
Patients with a history of multiple sclerosis had RNFL thinning that was detectable on SDOCT. Decreasing RNFL thickness in eyes with optic neuritis was found, and the odds of having optic neuritis were increased significantly with decreasing RNFL thickness. Average RNFL thinning with increasing duration of disease was an excellent predictor of a reported history of optic neuritis. SDOCT retinal imaging may represent a high-resolution, objective, noninvasive, and easily quantifiable in vivo biomarker of the presence of optic neuritis and severity of multiple sclerosis.
PMCID: PMC2946989  PMID: 20922034
multiple sclerosis; spectral-domain optical coherence tomography; optical coherence tomography; nerve fiber layer; nerve fiber layer thickness; optic neuritis
7.  The role of clinical parapapillary atrophy evaluation in the diagnosis of open angle glaucoma 
To determine if clinical evaluation of parapapillary atrophy (PPA) significantly improves the ability to distinguish open-angle glaucoma (OAG) patients from glaucoma suspects.
Patients in this study were under evaluation for glaucoma and had open angles, at least one reliable 24-2 SITA-standard automatic perimetry, and digital stereophotographs of the optic disc. PPA was identified clinically as a parapapillary region of absent (βPPA) or hyper/hypopigmented (αPPA) retinal pigment epithelium. A single masked observer evaluated photos for: vertical cup-to-disc ratio (CDR), clock hours of total and βPPA, βPPA as percentage width of the optic disc, presence or absence of βPPA at each disc quadrant, and ordinal rating of total PPA. Generalized linear models were used to determine odds of an abnormal or borderline glaucoma hemifield test (GHT) as a function of PPA variables and covariates; model fit was assessed using the log-likelihood ratio test.
Of 410 consecutive patients, 540 eyes (of 294 patients) met inclusion criteria. Mean age was greater among patients with abnormal compared with normal GHT (P < 0.001), but sex and race/ethnicity did not differ between groups (P ≥ 0.22). Age, central corneal thickness (CCT) and CDR (P ≤ 0.006), but not intraocular pressure (IOP) (P = 0.71), were significant univariable predictors of the odds of an abnormal GHT. All PPA parameters significantly predicted GHT (P ≤ 0.03), except presence of temporal βPPA (P = 0.25). Adjustment for age, CCT, IOP, and CDR reduced the association between PPA and GHT, and model fit was not greatly improved by addition of PPA variables.
Addition of most PPA parameters to a model already containing commonly assessed variables including age, CCT, IOP, and CDR does not significantly improve the ability to distinguish OAG patients from glaucoma suspects.
PMCID: PMC2938276  PMID: 20856591
glaucoma; visual fields; parapapillary atrophy; optic nerve

Results 1-7 (7)