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Ophthalmology 05/2013; 120(5):1099-1099.e1. · 5.45 Impact Factor
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ABSTRACT: PURPOSE: To characterize ocular surface discomfort and tear film parameters in a veteran population. Methods: Setting: Patients seen in the Miami Veterans Affairs eye clinic. Patient population: Male patients aged ≥50 with normal eyelid, corneal, and conjunctival anatomy. Patients filled out the Dry Eye Questionnaire 5 (DEQ5) and underwent measurement of tear film parameters. Main outcome measures: Frequency of ocular surface symptoms and correlation between symptoms and global, aqueous, and meibomian gland parameters. RESULTS: A total of 263 men participated in the study; 48% had DES based on the presence of severe symptoms. Many men had objective abnormalities in tear function measurements. Using Schirmer information, lid plugging, and meibomian quality to define objective DES, 176 patients (68%) had one or more abnormalities. Of these, 22 (8%) had aqueous tear deficiency, 124 (47%) lipid tear deficiency, and 30 (11%) a mixed pattern. When examining associations between individual clinical parameters and DEQ5 score, the only significant, but weak correlations were with the global parameters corneal staining (r=0.16) and TBUT (r=-0.15). Neither specific aqueous nor meibomian gland measurements were significantly correlated with the presence of symptoms. When considering all measured parameters in a regression model, 8% of the variability in symptoms was explained by the tear parameters. CONCLUSIONS: We found that ocular surface symptoms were prevalent in our population. Measurement of standard tear film parameters could not explain the degree of symptoms. This study highlights the need for future research regarding the mechanisms behind ocular surface discomfort in patients with tear film disturbances.
Investigative ophthalmology & visual science 02/2013; · 3.43 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate intravitreal bevacizumab as an adjuvant treatment to plaque brachytherapy in the treatment of choroidal melanoma.
This was a retrospective, consecutive study of 124 patients treated from 2007 to 2009 for choroidal melanoma with plaque brachytherapy. Patients were treated with I-125 plaque brachytherapy with 2 mm margins and 85 Gy to the tumor apex. Consecutive patients were injected intravitreally with 2.5 mg/0.1 mL bevacizumab at a site away from the primary tumor and immediately following plaque removal. Choroidal melanomas were observed using indirect ophthalmoscopy, wide-angle photography, and ultrasound. The main outcome measures were tumor volume, resolution of exudative retinal detachment, and visual acuity.
One hundred and twenty-four patients met our inclusion criteria and were included in the analysis. The mean patient age was 65.7 years, and the mean apical tumor height was 4.0 ± 2.7 mm and basal diameter was 12.7 ± 3.0 mm. Mean follow-up was 24 months. Prior to treatment, 100% of tumors had exudative retinal detachment, and pretreatment visual acuity was 20/55 (median 20/40). Tumor control was 100%, metastasis was 0% at last follow-up, and 89.8% had complete resolution of exudative retinal detachment, with a mean time to resolution of 3.36 months. At one month, 43% had complete resolution of exudative retinal detachment, which increased to 73% at 4 months. Visual acuity was 20/62 (median 20/40) at 4 months, with stabilization to 20/57 (median 20/40) at 8 months, 20/56 (median 20/30) at 12 months, and 20/68 (median 20/50) at 24 months. Tumor volume following combined therapy was shown to be reduced by 22.2% at 3 months, 28.9% at 6 months, 39.3% at 12 months, and 52.2% at 24 months (all P < 0.001). All patients tolerated the procedure well without systemic side effects.
Intravitreal bevacizumab may be used as an adjuvant agent following plaque brachytherapy. Treated choroidal melanomas show reduction in tumor volume as well as resolution of exudative retinal detachments.
Clinical ophthalmology (Auckland, N.Z.) 01/2013; 7:193-8.
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ABSTRACT: Purpose. To examine the differences in tear film parameters more than 3 months postsurgery in eyes with cataract surgery (surgical eyes) versus eyes without cataract surgery (nonsurgical eyes). Methods. 29 patients were seen at the Miami Veterans Affairs Medical Center (VAMC) who had cataract surgery by phacoemulsification in one eye more than 3 months prior to the study date and had no history of surgical intervention in their fellow eye. Tear film parameters were measured in both eyes and compared using McNemar tests for dichotomous variables and paired and single sample t-tests for continuous variables. Results. Mean patient age was 73 (standard deviation (SD): 11); 26 patients (90%) identified themselves as White and 7 (24%) as Hispanic. The mean number of days between surgery and this study was 952 (SD: 1109). There were no statistical differences between the surgical eye and the nonsurgical eye with respect to any of the measured tear film parameters. Confidence intervals around these differences were narrow enough to exclude a substantial effect of cataract surgery. The elapsed time between cataract surgery and measurement of the tear parameters did not appear to affect the difference in parameters between the two eyes. Conclusion. We found that eyes that had cataract surgery more than 3 months prior to testing had no differences in their tear film parameters compared to eyes without a history of surgery.
TheScientificWorldJOURNAL 01/2013; 2013:643764. · 1.66 Impact Factor
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Ophthalmology 10/2012; 119(10):2190-2190.e1. · 5.45 Impact Factor
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ABSTRACT: To identify predictors of ocular surface squamous neoplasm (OSSN) recurrence after operative resection.
Retrospective case series.
Three hundred eighty-nine consecutive patients who underwent excisional biopsy for OSSN lesions at the Bascom Palmer Eye Institute from January 1, 2001, to September 20, 2010.
Review of pathology records and patient charts.
Identification of factors predictive of OSSN recurrence.
Of 389 excised OSSN lesions, 44 recurred during follow-up. The 1-year recurrence rate was 10% and the 5-year recurrence rate was 21%, with a mean time to recurrence in those with a recurrence of 2.5 years (standard deviation, 3.4). Using the American Joint Committee on Cancer (AJCC) clinical staging system, T3 and T2 lesions portended a higher risk of recurrence compared with T1 (T2/T1 hazard ratio [HR], 2.05 [P = 0.04]; T3/T1 HR, 2.31 [P = 0.07]). In addition, a location characteristic that increased the risk of tumor recurrence was tarsal involvement (AJCC T3 stage lesion; HR, 4.12; P = 0.007). Nasal location was associated with a decreased risk of tumor recurrence (HR, 0.41; P = 0.008). Pathologic characteristics significantly associated with tumor recurrence were the presence of positive margins (HR, 2.73; P = 0.008) and higher grade lesions (carcinoma in situ and squamous cell carcinoma versus dysplasia; HR, 2.55; P = 0.02). Treatment with adjuvant cryotherapy significantly decreased the risk of tumor recurrence (HR, 0.51; P = 0.03). In those patients with positive margins, the use of postoperative topical interferon therapy lowered the recurrence rate to a level similar to that of patients with negative margins.
Certain patient and tumor factors are associated with a higher risk of OSSN recurrence after operative excision, such as tarsal tumor location and positive surgical margins. Postoperative adjuvant therapy should be considered in patients with high-risk OSSN characteristics.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Ophthalmology 06/2012; 119(10):1974-81. · 5.45 Impact Factor
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ABSTRACT: To study the scope of dry eye syndrome (DES) in veterans on a national level and to evaluate the relationship between psychiatric diagnoses and DES.
Case-control study.
Setting: Patients were seen in a Veterans Affairs (VA) eye clinic between 2006 and 2011. Patient population: Patients were divided into cases and controls with regard to their dry eye status (cases = ICD-9 code for DES plus dry eye therapy; controls = patients without ICD-9 code plus no therapy). Main outcome measures: The prevalence of DES and the influence of psychiatric diagnoses on the risk of DES.
A total of 2 454 458 patients were identified as either a dry eye case (n = 462 641) or control (n = 1 991 817). Overall, 19% of male patients and 22% of female patients had a diagnosis of DES, with female sex imparting an increased risk of DES at each decade compared to male sex (odds ratio [OR] 1.22-2.09). Several conditions were found to increase DES risk, including post-traumatic stress disorder (OR 1.92, 95% CI 1.91-1.94) and depression (OR 1.92, 95% CI 1.91-1.94) (analyses adjusted for sex and age). The use of several systemic medications was likewise associated with an increased risk of DES, including antidepressant medications (OR 1.97, 95% CI 1.79-2.17) and antianxiety medication (OR 1.74, 95% CI 1.58-1.91). Multivariate analysis (adjusted for age and sex) revealed that for psychiatric diagnoses, both the use of medication and the diagnosis remained significant risk factors when considered concomitantly, although the magnitude of each association decreased.
DES is a disease associated with depression and post-traumatic stress disorder, and is prevalent among male and female veterans receiving eye care services. The association could be driven by underlying disease physiology or medications used to treat psychiatric conditions. Regardless of the causal link, this suggests that individuals with a known psychiatric diagnosis should be questioned about dry eye symptoms and, if applicable, referred to an eye care physician.
American journal of ophthalmology 04/2012; 154(2):340-346.e2. · 3.83 Impact Factor
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ABSTRACT: To evaluate the impact of ocular surface symptoms on quality of life in a veteran population receiving eye care services.
Cross-sectional survey study.
setting: Miami Veterans Affairs Medical Center (VAMC). patient population: Patients seen at the eye clinic between June and August 2010 were asked to fill out the Dry Eye Questionnaire 5 (DEQ5) and the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire. main outcome measures: Correlation between ocular surface symptoms and functionality.
Four hundred eighty-nine patients elected to fill out the DEQ5 questionnaire (36% response rate). The mean age of respondents was 66 years (standard deviation 12). Ninety-four percent were male; 62% were white and 37% were black. Using the DEQ5 as a surrogate measure of ocular surface symptoms, 65% of respondents reported at least mild ocular surface symptoms (DEQ5 ≥6) and 27% of them reported severe symptoms (DEQ5 ≥12). Black subjects had a 2-fold increased risk of severe symptoms compared to white subjects (odds ratio 2.06, 95% confidence interval 1.33-3.19). Several medications were associated with a significantly increased risk of severe symptoms, including glaucoma medications (1.7-fold increase), antidepressants (2.3-fold increase), and antihistamines (2.1-fold increase). There was an inverse correlation between DEQ5 and IDEEL scores with regard to ability to perform activities of daily living (n = 391, r = -0.54, P < .001), emotional well-being (n = 386, r = -0.63, P < .001), and the ability to work (n = 205, r = -0.57, P < .001). Fifty percent of patients with severe symptoms had documentation that their symptoms were addressed during the visit.
Severe ocular surface symptoms reduce the quality of life of Miami VAMC veterans. Eye care professionals should be vigilant in eliciting ocular surface complaints from their patients.
American journal of ophthalmology 02/2012; 153(6):1061-66.e3. · 3.83 Impact Factor
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ABSTRACT: To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-d-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LH(BETA)T(AG) retinal tumors.
Seventeen-week-old LH(BETA)T(AG) retinal tumor eyes (n = 36) were treated with 2-FG and analyzed at 1 day and 1 week post a single treatment, and 1 day post a biweekly treatment for 3 weeks. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature. To assess tumor burden, sections were processed for standard hematoxylin-eosin (H&E) staining. Immunofluorescent techniques were used to stain for new and mature blood vessels.
Hypoxia and tumor burden reduction are significantly different between the treatment schedules used (P < 0.001). Eyes treated with 2-FG for 3 weeks showed a significant decrease in hypoxia (P = 0.001) and tumor burden (P = 0.009); whereas those treated with one injection and evaluated at 1 day and 1 week postinjection did not show a decrease in either hypoxia (P = 0.373 and P = 0.782, respectively) or tumor burden (P = 0.203 and P = 0.836, respectively). When evaluating the spatial distribution of hypoxic regions in the different areas of the tumor, 2-FG showed a differential effect on hypoxia depending on the area. Hypoxia was most decreased in the base of the treated eyes with a 95% reduction (P < 0.001).
This is the first study to elucidate that 2-FG treatment in retinoblastoma produces an impact on hypoxia and a concomitant decrease on tumor burden. In this study, the authors validate their previous studies by revealing that glycolytic inhibitors effectively target hypoxia in retinoblastoma tumors. The future application of 2-FG as an adjuvant treatment to standard chemotherapy may enhance the treatment of retinoblastoma.
Investigative ophthalmology & visual science 02/2012; 53(2):996-1002. · 3.43 Impact Factor
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ABSTRACT: PURPOSE: To evaluate the benefits of intravitreal bevacizumab in patients with visually compromising radiation maculopathy following iodine-125 plaque brachytherapy for uveal melanoma. METHODS: In this Institutional Review Board-approved, consecutive, retrospective study from 2006-2009 of patients maintaining 20/50 or better vision following treatment for visually compromising radiation maculopathy, patients were evaluated with spectral domain optical coherence tomography at 2-4 month intervals following plaque removal. Treatment with intra-vitreal bevacizumab commenced at the first signs of radiation vasculopathy on spectral domain optical coherence tomography with associated decreased best corrected visual acuity, followed by repeat injections for recurrent or persistent vasculopathic changes. RESULTS: At 3 years following plaque brachytherapy, 81 of 159 (50.9%) patients treated for radiation maculopathy demonstrated 20/50 or better vision at median follow up of 36 months, which demonstrates significant improvement in vision as compared to the Collaborative Ocular Melanoma Study (P < 0.0001). These 81 patients were given a mean of five injections (range 1-17) over a mean of 17.6 months (range 1-54 months), starting at 15.8 months (range 3-50 months) after plaque brachytherapy. For those eyes that maintained 20/50 or better vision at the final follow-up, pretreatment mean best corrected visual acuity of 20/43 improved to 20/31. CONCLUSION: This study demonstrates that spectral domain optical coherence tomography can detect early vasculopathic changes secondary to radiation maculopathy and that prompt treatment with intravitreal bevacizumab may delay vision loss and maintain or possibly improve visual acuity in half of eyes diagnosed with radiation maculopathy. Radiation maculopathy remains a therapeutically manageable morbidity associated with radiation therapy for posterior uveal melanoma.
Clinical Ophthalmology 01/2012; 6:1739-1748.
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ABSTRACT: To evaluate the prevalence of dry eye syndrome (DES) and its associated risk factors in a US Veterans Affairs population receiving ocular care services.
Retrospective study.
settings: Patients were seen in the Miami and Broward Veterans Affairs eye clinics between 2005 and 2010. patients population: Patients were divided into cases and controls with regard to their dry eye status (cases = ICD9 code for DES plus dry eye therapy; controls = patients without ICD9 code plus no therapy). main outcome measures: The prevalence of DES and its associated risk factors.
A total of 16 862 patients were identified as either a dry eye case (n = 2056) or control (n = 14 806). Overall, 12% of male and 22% of female patients had a diagnosis of DES, with female gender imparting a 2.40 increased risk (95% confidence interval [CI] 2.04-2.81) over male gender. Several medical conditions were found to increase DES risk including post-traumatic stress disorder (odds ratio [OR] 1.97, 95% CI 1.75-2.23), depression (OR 1.91, 95% CI 1.73-2.10), thyroid disease (OR 1.81, 95% CI 1.46-2.26), and sleep apnea (OR 2.20, 95% CI 1.97-2.46) (all analyses adjusted for gender and age). The use of several systemic medications, including anti-depressant medications (OR 1.97, 95% CI 1.79-2.17), anti-anxiety medication (OR 1.74, 95% CI 1.58-1.91), and anti-benign prostatic hyperplasia medications (OR 1.68, 95% CI 1.51-1.86), was likewise associated with an increased risk of DES.
The prevalence of DES was found to be high in both men and women in our eye care population. This is the first study to demonstrate that in a veteran population, several diagnoses were significantly associated with DES, including post-traumatic stress disorder and depression.
American journal of ophthalmology 06/2011; 152(3):377-384.e2. · 3.83 Impact Factor
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ABSTRACT: To evaluate the long-term results of femtosecond laser-assisted anterior lamellar keratoplasty (FALK) for anterior corneal pathologies.
Retrospective, noncomparative, interventional case series.
Thirteen consecutive patients who underwent FALK for anterior corneal pathologies.
Femtosecond laser-assisted sutureless anterior lamellar keratoplasty.
Best spectacle-corrected visual acuity (BSCVA), manifest refraction, need for adjunctive surgery, and complications.
Follow-up ranged from 12 to 69 months (mean = 31 months). The BSCVA was significantly improved over preoperative values at the 12-, 18-, 24-, and 36-month visits. A BSCVA greater than 20/30 was achieved in 54% of patients at the 12-month visit when all 13 patients were available for follow-up, in 50% and 33% of patients at the 18- and 24-month visits, respectively, when 12 patients were available, and in 60% and 50% of patients at the 36- and 48-month visits when 5 and 2 patients were available, respectively. The BSCVA of the eye that completed the 60- and 70-month visits was 20/50. Patients achieved a mean gain of 5 lines of BSCVA at the 6-, 12-, 18-, and 24-month visits, 4 lines at the 36-month visit, 5 lines at the 48-month visit, and 6 lines at the 60- and 72-month visits. Two patients lost a mean of 1.5 lines of BSCVA because surface haze developed after photorefractive keratectomy (PRK) and granular dystrophy recurred in the graft. At a mean of 5 weeks postoperatively, 83.3% of patients achieved BSCVA within 2 lines of that recorded at the 24-month visit. At the 12-month visit, mean spherical equivalent and refractive astigmatism were -0.4 diopters (D) and 2.2 D, respectively, with no significant shift from preoperative values or values recorded in different follow-up visits. Adjunctive surgeries included phototherapeutic keratectomy, PRK, cataract extraction, and epithelial ingrowth debridement. Complications included residual corneal pathology, mild interface haze, anisometropia, recurrence of pathology, haze after adjunctive PRK, dry eye, epithelial ingrowth, and suspicious ectasia.
Femtosecond laser-assisted sutureless anterior lamellar keratoplasty improves the BSCVA of patients with anterior corneal pathologies with rapid visual rehabilitation and no significant induced astigmatism. Our preliminary results indicate that FALK results remained stable throughout the follow-up period.
Ophthalmology 02/2011; 118(2):315-23. · 5.45 Impact Factor
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Samuel K Houston,
Yolanda Piña,
Timothy G Murray,
Hinda Boutrid,
Colleen Cebulla,
Amy C Schefler,
Wei Shi,
Magda Celdran, William Feuer,
Jaime Merchan,
Ted J Lampidis
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ABSTRACT: The purpose of this study was to evaluate the effect of optimally timed combination treatment with angiogenic and glycolytic inhibitors on tumor burden, hypoxia, and angiogenesis in advanced retinoblastoma tumors.
LH(BETA)T(AG) mice (n =30) were evaluated. Mice were divided into 5 groups (n =6) and received injections at 16 weeks of age (advanced tumors) with a) saline, b) anecortave acetate (AA), c) 2-deoxyglucose (2-DG), d) AA +2-DG (1 day post-AA treatment), or e) AA +2-DG (1 week post-AA treatment). Eyes were enucleated at 21 weeks and tumor sections were analyzed for hypoxia, angiogenesis, and tumor burden.
Eyes treated with 2-DG 1 day post-AA injection showed a 23% (P =0.03) reduction in tumor burden compared with 2-DG alone and a 61% (P < 0.001) reduction compared with saline-treated eyes. Eyes treated with 2-DG 1 week post-AA injection showed no significant decrease in tumor burden compared with 2-DG alone (P = 0.21) and a 56% (P < 0.001) decrease in comparison with saline-treated eyes. 2-DG significantly reduced the total density of new blood vessels in tumors by 44% compared to saline controls (P < 0.001), but did not affect the density of mature vasculature.
Combination therapy with angiogenic and glycolytic inhibitors significantly enhanced tumor control. Synergistic effects were shown to be dependent on the temporal course of treatment, emphasizing optimal timing. 2-DG was shown to reduce the density of neovessels, demonstrating an antiangiogenic effect in vivo. As a result, angiogenic and glycolytic inhibitors may have significant potential as alternative therapies for treating children with retinoblastoma.
Clinical Ophthalmology 01/2011; 5:129-37.
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ABSTRACT: The aim of this study was to evaluate the changes in tumor burden and hypoxia in the LH(BETA)T(AG) retinal tumors after treatment with a focal, single-modality, and combination therapy using periocular carboplatin and 2-deoxy-d-glucose (2-DG).
Seventeen-week-old LH(BETA)T(AG) transgenic mice (n = 25) were treated with periocular injections of varying doses of 2-DG (62.5, 125, 250, 500 mg/kg) to obtain a dose response. Same-aged mice (n = 30) received periocular injections of saline, carboplatin, and 2-DG. Mice were divided into six groups: saline; carboplatin (31.25 μg/20 μL, subtherapeutic dose); 2-DG (250 mg/kg); 2-DG (500 mg/kg); carboplatin (31.25 μg/20 μL) and 2-DG (250 mg/kg); and carboplatin (31.25 μg/20 μL) and 2-DG (500 mg/kg). Injections were administered twice weekly for three consecutive weeks. Eyes were enucleated at 20 weeks of age, snap frozen, and analyzed for hypoxic regions and tumor volume.
The difference in percentage of hypoxia after treatment with 500 mg/kg 2-DG was statistically significant from the other dose groups (P < 0.015). The difference in tumor burden was statistically significant from the 250 mg/kg dose (P < 0.015) and 500 mg/kg dose (P < 0.001). Highly significant differences were found between the treatment types for tumor burden, percentage of hypoxia, and pimonidazole intensity (P < 0.001). Tumor burden decreased significantly after all forms of treatment (P < 0.001); however, tumor burden became significantly more reduced after treatment with combination therapy of carboplatin and 2-DG than with either treatment alone (P < 0.001). The percentage of hypoxia and pimonidazole intensity decreased after treatment with 2-DG alone and in combination with carboplatin (P < 0.001) in all treatment groups using 2-DG regardless of the 2-DG dose used. There was no percentage reduction of hypoxia after treatment with carboplatin alone (P = 0.25).
This study demonstrates the efficacy of focal, periocular 2-DG as an adjunct to carboplatin chemotherapy to decrease both intratumoral hypoxia and tumor burden. Hypoxia is increasingly present in advanced disease of LH(BETA)T(AG) retinal tumors. The use of glycolytic inhibitors as a therapeutic strategy has the potential to enhance current retinoblastoma treatments.
Investigative ophthalmology & visual science 12/2010; 51(12):6149-56. · 3.43 Impact Factor
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Anat Galor, William Feuer,
John H Kempen,
R Oktay Kaçmaz,
Teresa L Liesegang,
Eric B Suhler,
C Stephen Foster,
Douglas A Jabs,
Grace A Levy-Clarke,
Robert B Nussenblatt,
James T Rosenbaum,
Jennifer E Thorne
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ABSTRACT: To evaluate how smoking affects the time to disease quiescence and time to disease recurrence in patients with ocular inflammation.
A retrospective cohort study of patients with ocular inflammation who were followed longitudinally and had smoking information available in the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study database.
Among 2676 patients with active ocular inflammation, smokers were more likely to have bilateral ocular disease and poorer visual acuity on presentation compared with non-smokers and previous smokers. In a multivariate analysis, there was no statistically significant difference in the time to disease quiescence between groups. However, the median time to recurrence of ocular inflammation was statistically significantly longer for non-smokers (9.4 months) and for previous smokers (10.7 months) than for current smokers (7.8 months) (p=0.02). The RR of ocular inflammation recurrence was higher for smokers than for non-smokers (adjusted HR=1.19, 95% CI 1.03 to 1.37) and tended towards significance in previous smokers (adjusted HR=1.11, 95% CI 0.93 to 1.35).
Smoking was associated with an increased likelihood of bilateral ocular inflammation and reduced vision upon presentation, and an increased risk of recurrence compared with not smoking. These results suggest that patients with ocular inflammation should be counselled to stop smoking as part of routine management.
The British journal of ophthalmology 07/2010; 94(7):848-53. · 2.92 Impact Factor
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ABSTRACT: Gelatinases, matrix metalloproteinase (MMP)-2, and MMP-9 are known for their importance in angiogenesis and tumor biology. The purpose of this study was to test the hypothesis that anecortave acetate (AA) decreases transgenic retinoblastoma (RB) tumor burden by modulating gelatinase activity.
To assess the possible gelatinase modulation after AA treatment, a single subconjunctival injection of AA (300 microg) was delivered to the right eyes of 10-week-old LH(BETA)T(AG) mice. Eyes were evaluated for gelatinase expression and activity by gel and in situ zymography at 24 hours, 48 hours, and 1 week after treatment.
Gel zymography of whole eye extracts and in situ zymography of retinal tumors showed strong gelatinase expression and activity within transgenic RB tumors. AA treatment in RB transgenic mice resulted in a significant decrease of gelatinase activity 1 week after AA treatment. Surprisingly, there was an initial transient upregulation of MMP-9 activity in whole eye extracts at 24 and 48 hours after AA treatment in both LH(BETA)T(AG) transgenic and wild-type mice. This increase was not observed in the tumors.
As suggested by our data, inhibition of gelatinase activity appears to be a mechanism of action of AA. AA treatment results in a decrease in gelatinase activity that correlates with the significant decrease in tumor burden shown by the authors' previous studies. However, the significance of the initial, transient upregulation of gelatinase by AA injection is unknown, and further studies are warranted. Combining antiangiogenic agents with multiple mechanisms of action has the potential to enhance RB tumor control.
Investigative ophthalmology & visual science 06/2010; 51(6):2860-4. · 3.43 Impact Factor
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Yolanda Piña,
Hinda Boutrid,
Timothy G Murray,
Martine J Jager,
Colleen M Cebulla,
Amy Schefler,
Long V Ly,
Armando Alegret,
Magda Celdran, William Feuer,
Maria-Elena Jockovich
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ABSTRACT: To determine the distribution of tumor-associated macrophages (TAMs) during retinoblastoma tumor development, examine the contribution of bone marrow-derived TAMs in retinoblastoma tumors, and evaluate the supportive role of TAMs in tumor growth in a transgenic retinoblastoma mouse model.
The time course of macrophage infiltration in transgenic retinoblastoma tumors was assessed by immunohistochemistry at different time points in tumorigenesis. The origin of TAMs in transgenic retinoblastoma tumors was determined by transplanting 10(7) bone marrow cells from green fluorescent protein (GFP)-positive 16-week-old mice into age-matched, irradiated LH(BETA)T(AG) mice via tail vein injections. Macrophage depletion was performed by subconjunctival (SC) delivery of liposomal clodronate.
The density of TAMs increased from 4 to 12 weeks of age in mice with small to medium tumors (P = 0.037) and remained stable in the later stages of disease (i.e., 16 weeks old with large tumors; P = 0.20). In 16-week-old mice, 38% (2.5 +/- 3.2 cells per 400x high-power field) of TAMs were GFP-positive, bone marrow-derived macrophages. Total TAM depletion was associated with a significant decrease in the expression levels of MMP-9 (P = 0.014) and mature vessels (P < 0.001) and a nonsignificant decrease in the density of neovessels (P = 0.94). The density of M2-polarized TAMs did not change significantly after TAM depletion (P = 0.68). After M1-polarized TAM depletion, the tumor burden increased (P = 0.056).
This work extends understanding of the complex role that macrophages play in retinoblastoma. Macrophage modulation in the tumor microenvironment is a critical factor in retinoblastoma tumor progression.
Investigative ophthalmology & visual science 05/2010; 51(5):2671-7. · 3.43 Impact Factor
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Mohamed Abou Shousha,
Victor L Perez,
Jianhua Wang,
Takeshi Ide,
Shuliang Jiao,
Qi Chen,
Victoria Chang,
Nancy Buchser,
Sander R Dubovy, William Feuer,
Sonia H Yoo
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ABSTRACT: To demonstrate the capability of ultra-high-resolution (UHR) anterior segment optical coherence tomography (OCT) to image Descemet's membrane (DM) and measure its thickness in vivo. (2) To evaluate the use of DM characteristics and thickness in the diagnosis of Fuchs' dystrophy.
Case-control study.
Twenty eyes of 12 Fuchs' dystrophy patients, 20 eyes of 13 young normal, and 20 eyes of 15 elderly normal subjects.
Subjects were imaged using novel, custom-built UHR-OCT. Images were used to describe the characteristics of DM. Custom-made software was used to measure DM thickness and central corneal thickness (CCT). Specimens of DM obtained from Fuchs' dystrophy patients who underwent endothelial keratoplasty (EK) were histopathologically examined. Regression analyses were used to assess the correlation of DM thickness measured by UHR-OCT in vivo and by light microscopy and to determine the intergroup correlations between age, CCT, and DM thickness.
We assessed DM characteristics and thickness, CCT, and age.
Using UHR-OCT, the DM seemed in normal young subjects as a single, opaque, smooth line and in normal elderly subjects as a band of 2 smooth opaque lines with a translucent space in between. In Fuchs' dystrophy, DM appeared as a thickened band of 2 opaque lines; the anterior line was smooth whereas the posterior line had a wavy and irregular appearance with areas of localized thickenings. The DM thickness measured in vivo by UHR-OCT correlated significantly with that measured by light microscopy in 5 Fuchs' dystrophy eyes that underwent EK. The average central thicknesses of DM in normal young, in normal elderly and in Fuchs' dystrophy eyes were 10+/-3, 16+/-2, and 34+/-11 microm, respectively (P<0.001). There was a significant correlation between age and DM thickness only in normal groups. In Fuchs' dystrophy patients, there was a significant correlation between CCT and DM thickness that was not significant for normal groups.
Ultra-high-resolution OCT is an innovative technique for the in vivo imaging of DM. Determining DM characteristics and thickness by UHR-OCT could be a new approach for the diagnosis of Fuchs' dystrophy.
Ophthalmology 02/2010; 117(6):1220-7. · 5.45 Impact Factor
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Kimberly E Stepien,
Philip J Rosenfeld,
Carmen A Puliafito, William Feuer,
Wei Shi,
Luma Al-Attar,
Sander R Dubovy,
Timothy G Murray,
Janet L Davis,
Wen-Hsiang Lee,
Stephen G Schwartz,
William E Smiddy,
Audina M Berrocal,
Harry W Flynn
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ABSTRACT: To compare outcomes after switching from intravitreal bevacizumab (Avastin) to ranibizumab (Lucentis) in patients with neovascular age-related macular degeneration (AMD).
A retrospective review was performed of patients with neovascular AMD who were switched from treatment with intravitreal bevacizumab to intravitreal ranibizumab once ranibizumab became commercially available. All reviewed patients had at least three bevacizumab injections before being switched to ranibizumab. The treatment outcomes included comparisons of visual acuity and dosing frequency while receiving both drugs.
Eighty-four eyes met the inclusion criteria. Mean baseline visual acuity was 20/100. Mean duration of bevacizumab treatment was 7.1 months followed by 7.3 months with ranibizumab (P = 0.68). Best-obtained visual acuity during treatment was 20/63 with bevacizumab and 20/63 with ranibizumab (P = 0.5). Last mean visual acuity after receiving bevacizumab at the time of the first ranibizumab injection was 20/80. Mean visual acuity at the last ranibizumab follow-up visit was 20/80 (P = 0.49). Mean injection rates per month while receiving bevacizumab and ranibizumab were 0.66 (P = 0.98).
In this subset of patients with neovascular AMD switched from bevacizumab to ranibizumab therapy, there were no apparent differences in visual acuity outcomes or injection rates. Larger prospective studies are under way to directly compare these drugs for the treatment of neovascular AMD.
Retina (Philadelphia, Pa.) 09/2009; 29(8):1067-73. · 2.93 Impact Factor
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ABSTRACT: To evaluate the recurrence rates of herpes simplex virus (HSV) keratitis in contact lens wearers compared with non-contact lens wearers.
Retrospective cohort study. Charts of patients diagnosed with HSV keratitis seen at the Cleveland Clinic between January 2001 and December 2004 were reviewed.
One hundred seventeen patients were included in this study: 21 contact lens wearers and 96 non-contact lens wearers. Contact lens wearers were found to have a higher median recurrence rate (0.4 episodes/year) compared with non-contact lens wearers (0.2 episodes/year) (P=0.02). A multivariate regression evaluating factors predictive of the number of recurrences found that contact lens use remained a significant predictive variable (P=0.02) when accounting for patient demographic and disease factors and variable follow-up time.
Patients with a history of HSV keratitis should be counseled about the potential increased risk of recurrence that may be associated with contact lens wear.
Eye & contact lens 07/2009; 35(4):185-7.
