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1.  Vascular endothelial growth factor trap-eye (Aflibercept) for the management of diabetic macular edema 
World Journal of Diabetes  2013;4(6):303-309.
Diabetic retinopathy (DR) is the most common cause of visual loss among working age individuals. Diabetic macular edema (DME) is an important complication of DR that affects around one third of the patients with DR. Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor (VEGF) antagonists. The index review discusses aflibercept (EYLEA®-Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, and Bayer Healthcare Pharmaceuticals, Berlin, Germany) in the context of other VEGF antagonists currently available for the treatment of DME. A systematic search of literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication. Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A (VEGF-A) along with a longer duration of action as compared to other VEGF antagonists. Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring. Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases. However, further studies are indicated to confirm the role, safety, and efficacy of aflibercept for DME.
doi:10.4239/wjd.v4.i6.303
PMCID: PMC3874490  PMID: 24379921
Diabetic macular edema; Diabetic retinopathy; Anti-vascular endothelial growth factor agents; Vascular endothelial growth factor trap-eye; Aflibercept; EYLEA
2.  Surgery for post-vitrectomy cataract 
Background
Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery.
Objectives
The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes.
Search methods
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMED-LINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 May 2013.
Selection criteria
We planned to include randomized and quasi-randomized controlled trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy.
Data collection and analysis
Two authors screened the search results independently according to the standard methodological procedures expected by The Cochrane Collaboration.
Main results
We found no randomized or quasi-randomized controlled trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy surgery.
Authors' conclusions
There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include gain of vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six-month) and long-term (one-year or two-year) outcomes should be examined.
doi:10.1002/14651858.CD006366.pub3
PMCID: PMC4258709  PMID: 24357418
*Cataract Extraction; Cataract [*etiology]; Quality of Life; Randomized Controlled Trials as Topic; Visual Acuity; Vitrectomy [*adverse effects]; Adult; Humans
3.  Surgery for post-vitrectomy cataract 
Background
Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit benefit from cataract surgery.
Objectives
The objective of this review was to evaluate benefits and harms of surgery for post-vitrectomy cataract.
Search methods
We searched CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (January 1950 to April 2011), EMBASE (January 1980 to April 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to April 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.anzctr.org.au). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 19 April 2011.
Selection criteria
We planned to include randomized and quasi-randomized trials comparing cataract surgery with no surgery in adult patients who developed cataract following vitrectomy.
Data collection and analysis
Two authors screened the search results independently. No studies were eligible for inclusion in the review.
Main results
We found no randomized or quasi-randomized trials comparing cataract surgery with no cataract surgery for patients who developed cataracts following vitrectomy.
Authors’ conclusions
There is no evidence from randomized or quasi-randomized controlled trials on which to base clinical recommendations for surgery for post-vitrectomy cataract. There is a clear need for randomized controlled trials to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the pathologic process in the contralateral eye. Outcomes assessed in such trials may include gain of 8 or more letters vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality of life, and adverse events such as posterior capsular rupture. Both short-term (six months) and long-term (one-year or two-years) outcomes should be examined.
Plain language summary
Surgery for post-vitrectomy cataract
Vitrectomy or surgery for removal of vitreous, the substance in the center of the eye, for several conditions can result in formation or acceleration of cataract, specifically nuclear sclerotic cataract (that due to hardening and opacification of the central portion of the lens in the eye). We found no randomized trials evaluating the benefits and/or risks of cataract surgery following vitrectomy. Since cataract surgery may lead to deterioration of vision due to worsening or recurrence of the condition that prompted the vitrectomy, its role in these patients remains uncertain. Future trials should stratify participants by age, the retinal disorder leading to surgery (vitrectomy) and the status of the disease process in the opposite eye. Outcomes relevant to patients such as a gain of 8 or more letters of vision on the ETDRS (Early Treatment Diabetic Retinopathy Study) scale, quality of life measures, and important adverse events should be examined both in the short-term (six months after surgery) and in the long-term (one-year to two-years after surgery).
doi:10.1002/14651858.CD006366.pub2
PMCID: PMC4257703  PMID: 18646150
4.  Long-term Outcomes in Ranibizumab-Treated Patients With Retinal Vein Occlusion; The Role of Progression of Retinal Nonperfusion 
American journal of ophthalmology  2013;156(4):693-705.
PURPOSE
To determine the percentage of ranibizumab-treated patients with retinal vein occlusion (RVO) who had resolution of edema for at least 6 months after the last injection, along with factors and outcomes that correlate with resolution.
DESIGN
Post hoc analysis of open-label clinical trial.
METHODS
Twenty patients with branch RVO (BRVO) and 20 with central RVO (CRVO) received ranibizumab monthly for 3 months and as needed for recurrent/persistent macular edema, no more frequently than every 2 months. Patients still requiring injections after month 40 received scatter and grid laser photocoagulation to try to reduce the need for injections. Main outcome measures included the percentage of patients who had resolution of edema, change in best-corrected visual acuity (BCVA) from baseline, and change in area of retinal nonperfusion in central subfields.
RESULTS
Nine patients with BRVO (45%) had edema resolution from injections alone after a mean of 20.2 months, 4 resolved after addition of laser, 4 were unresolved through 72 months, and 3 exited prior to resolution. Five patients with CRVO (25%) resolved from injections alone after a mean of 14.0 months, 8 remained unresolved through 72 months despite addition of laser, and 7 exited prior to resolution. For BRVO or CRVO, there was a negative correlation between posterior retinal nonperfusion area and BCVA at months 18, 24, and 36 (P < .05).
CONCLUSIONS
In patients with RVO, infrequent ranibizumab injections to control edema may not be sufficient to prevent progression of retinal nonperfusion, which may contribute to loss of visual gains.
doi:10.1016/j.ajo.2013.05.039
PMCID: PMC4030598  PMID: 24053892
5.  Evaluation of real-world mobility in age-related macular degeneration 
BMC Ophthalmology  2015;15:9.
Background
Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility.
Methods
Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures.
Results
In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11).
Conclusion
AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients.
doi:10.1186/1471-2415-15-9
PMCID: PMC4328075  PMID: 25636376
Age-related macular degeneration; Physical activity; Mobility
6.  Choroidal Neovascularization Regression on Fluorescein Angiography after VEGF Blockade 
Case Reports in Ophthalmology  2012;3(3):384-388.
Background
Intravitreal vascular endothelial growth factor (VEGF) inhibitors stabilize vision in a majority of patients with neovascular age-related macular degeneration (AMD) and can improve vision in almost 40% of patients. However, some individuals who respond to anti-VEGF treatment still lose vision due to the formation of geographic atrophy (GA). While optical coherence tomography is often the primary imaging modality used, fluorescein angiography (FA) can provide useful information on GA development after choroidal neovascularization (CNV) regression.
Methods
A retrospective chart review was conducted to evaluate the changes seen on FA over a 47-month period for 3 patients with neovascular AMD treated with anti-VEGF inhibitors.
Results
All 3 patients were initially noted to have subfoveal CNV due to AMD at baseline; they were followed up monthly and treated on an as needed basis for at least 47 months with intravitreal VEGF inhibitors. All subjects had regression of their CNV lesions after VEGF blockade. Two subjects developed foveal atrophy.
Conclusions
This case series depicts the changes on FA seen over a 4-year period and shows that GA can occur with regression of CNV after treatment with VEGF inhibitors.
doi:10.1159/000338969
PMCID: PMC3506058  PMID: 23185181
Choroidal neovascularization; Fluorescein angiography; Age-related maculopathies
7.  Diabetic retinopathy: variations in patient therapeutic outcomes and pharmacogenomics 
Diabetes and its microvascular complications in patients poses a significant challenge and constitutes a major health problem. When it comes to manifestations in the eye, each case of diabetic retinopathy (DR) is unique, in terms of the phenotype, genotype, and, more importantly, the therapeutic response. It is therefore important to identify factors that distinguish one patient from another. Personalized therapy in DR is a new trend aimed at achieving maximum therapeutic response in patients by identifying genotypic and phenotypic factors that may result in less than optimal response to conventional therapy, and consequently, lead to poorer outcome. With advances in the identification of these genetic markers, such as gene polymorphisms and human leucocyte antigen associations, as well as development of drugs that can target their effects, the future of personalized medicine in DR is promising. In this comprehensive review, data from various studies have been analyzed to present what has been achieved in the field of pharmacogenomics thus far. An insight into future research is also provided.
doi:10.2147/PGPM.S52821
PMCID: PMC4271791  PMID: 25548526
personalized medicine; therapeutic variation; genomic markers; genotype; phenotype; VEGF mutation; polymorphism; linkage; mutation; responder
8.  Comparison of Time- and Spectral-Domain Optical Coherence Tomography in Management of Diabetic Macular Edema 
Purpose.
Some clinical trials that proved the benefits of anti-VEGF therapy for diabetic macular edema (DME) based retreatment decisions on visual acuity and time-domain ocular coherence tomography (TD-OCT) central subfield thickness changes since the last treatment. This study assessed the impact of TD-OCT followed by spectral domain (SD)-OCT on as needed treatment decision-making in the management of DME with anti-VEGF medications.
Methods.
Patients previously treated for DME with anti-VEGF medications in the Retina Division of the Wilmer Eye Institute, following an institutional review board–approved informed consent process, underwent clinical examination, TD-, and SD-OCT imaging. Their retina specialists recorded whether additional anti-VEGF therapy was recommended and their level of certainty in the decision after performing a clinical examination and reviewing a TD-OCT, and then again after reviewing a SD-OCT.
Results.
Data were collected for 129 treatment decision pairs involving 67 eyes from 46 subjects. Nonconcordant decisions occurred in 9 (7%) treatment decision pairs. In 7 of these (5%, 95% confidence interval [CI]: 2%–11%), the addition of SD-OCT changed the retina specialist's decision from not recommending to recommending retreatment. The addition of SD-OCT increased the certainty of the retina specialist in 36% (95% CI: 27%–45%) of all treatment decision pairs.
Conclusions.
Spectral-domain OCT does not appear to change the ultimate treatment decision or increase the level of certainty of the retina specialist relative to TD-OCT in most cases of DME under anti-VEGF management in clinical practice. The few nonconcordant decisions appear to trend toward recommending more anti-VEGF therapy following SD-OCT.
Spectral-domain optical coherence tomography (SD-OCT) does not appear to change the ultimate treatment decision or increase the level of certainty of the retina specialist relative to time-domain OCT in most cases of diabetic macular edema under anti-VEGF management in clinical practice.
doi:10.1167/iovs.13-13049
PMCID: PMC3945899  PMID: 24526445
optical coherence tomography; macular edema; diabetic retinopathy
9.  Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development 
BioMed Research International  2013;2013:830837.
As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.
doi:10.1155/2013/830837
PMCID: PMC3844201  PMID: 24319688
10.  Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin a-4 phosphate 
Background
This study was designed to assess the safety, tolerability, and efficacy of intravenous infusion of CA4P in patients with neovascular age-related macular degeneration (AMD).
Methods
Prospective, interventional, dose-escalation clinical trial. Eight patients with neovascular AMD refractory to at least 2 sessions of photodynamic therapy received CA4P at a dose of 27 or 36 mg/m2 as weekly intravenous infusion for 4 consecutive weeks. Safety was monitored by vital signs, ocular and physical examinations, electrocardiogram, routine laboratory tests, and collection of adverse events. Efficacy was assessed using retinal fluorescein angiography, optical coherence tomography, and best corrected visual acuity (BCVA).
Results
The most common adverse events were elevated blood pressure (46.7%), QTc prolongation (23.3%), elevated temperature (13.3%), and headache (10%), followed by nausea and eye injection (6.7%). There were no adverse events that were considered severe in intensity and none resulted in discontinuation of treatment. There was reduction of the excess foveal thickness by 24.15% at end of treatment period and by 43.75% at end of the two-month follow-up (p = 0.674 and 0.161, respectively). BCVA remained stable throughout the treatment and follow-up periods.
Conclusions
The safety profile of intravenous CA4P was consistent with that reported in oncology trials of CA4P and with the class effects of vascular disruptive agents; however, the frequency of adverse events was different. There are evidences to suggest potential efficacy of CA4P in neovascular AMD. However, the level of systemic safety and efficacy indicates that systemic CA4P may not be suitable as an alternative monotherapy to current standard-of-care therapy.
Trial registration
ClinicalTrials.gov NCT01570790.
doi:10.1186/2050-6511-14-7
PMCID: PMC3552984  PMID: 23316779
Angiogenesis; Neovascularization; Ocular pharmacology; Retinal degeneration; Combretastatin A-4 Phosphate; CA4P; Vascular disrupting agents; VDA
11.  Ultra-wide-field retinal imaging in the management of non-infectious retinal vasculitis 
Background
The purpose of this study is to describe and quantify the benefit of ultra-wide-field imaging and fluorescein angiography (FA) in the management of non-infectious retinal vasculitis. In this prospective observational cohort series, patients with non-infectious retinal vasculitis were evaluated and enrolled by four investigators from the Divisions of Retina and Ocular Immunology at the Wilmer Eye Institute. In each patient, disease activity and the need for management changes were assessed, based on clinical examination with or without standard (60°) imaging and then with the addition of ultra-wide-field pseudo-color scanning laser ophthalmoscope (SLO) images and FA using the Optos ultra-wide-field SLO (Optos Panoramic 200MA™, Optos PLC, Dunfermline, Scotland, UK). A standardized questionnaire was completed by each investigator at the time of the clinical evaluation.
The primary outcome was the percentage of patients whose management was changed by clinical examination and standard FA, compared with clinical examination plus ultra-wide-field imaging. The secondary outcome was the percentage of patients whose disease was determined to be active based on each modality.
Results
Seventy-one visits from 23 patients were reviewed and analyzed. Based on examination plus ultra-wide-field imaging and ultra-wide-field angiography, disease activity was detected in 48/71 (68%) compared with 32/71 (45%) based on examination and standard FA (P = 0.0095). Based on the clinical examination alone, the decision to alter management was made in 4 of 71 visits (6%), and an additional 3 of 71 (4%) based on simulated standard FA. The addition of ultra-wide-field SLO pseudo-color images altered management in an additional 10/71 visits (14%), and 36/71 (51%) with the addition of ultra-wide-field FA.
Conclusions
Ultra-wide-field fluorescein imaging and angiography can provide additional information that may be important and relevant in the management of retinal vasculitis.
doi:10.1186/1869-5760-3-30
PMCID: PMC3610112  PMID: 23514542
Non-infectious retinal vasculitis; Fluorescein angiography; Ultra-wide-field imaging
12.  Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study 
Background
The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.
Results
At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug.
Conclusion
Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.
doi:10.1186/1869-5760-3-32
PMCID: PMC3610181  PMID: 23514595
Sirolimus; mTOR; Uveitis; Intravitreal; Subconjunctival
13.  Longitudinal spectral domain optical coherence tomography changes in eyes with intraocular lymphoma 
Background
Cases of patients with primary intraocular lymphoma (PIOL) were retrospectively analyzed to describe the longitudinal intra-retinal morphological changes in PIOL as visualized on images obtained by spectral domain optical coherence tomography (SD-OCT).
Results
In a retrospective case series, Heidelberg Spectralis SD-OCT images obtained in the longitudinal evaluation of patients with biopsy-proven PIOL were analyzed and assessed. The images were graded for the presence of macular edema (ME), pigment epithelial detachment (PED), subretinal fluid (SRF), and hyperreflective signals. SD-OCT scans of five eyes from five patients were assessed. Patients showed signs of inflammation, such as ME and SRF, which were resolved with treatments in some cases. Hyperreflective signals were found in all eyes in the form of nodules or bands across the retina, with the highest frequency of appearance in the ganglion cell layer, inner plexiform layer, photoreceptor layer, and retinal pigment epithelium; such signals increased with the progression of PIOL.
Conclusion
SD-OCT may be employed to monitor the progression of PIOL. Hyperreflective signals on OCT may correspond with increase in disease activities, along with other findings such as ME, PED, and SRF.
doi:10.1186/1869-5760-3-59
PMCID: PMC3847273  PMID: 24011267
Spectral domain optical coherence tomography (SD-OCT); Primary intraocular lymphoma; Primary retinal lymphoma; Primary vitreoretinal lymphoma
14.  Comparison of Time Domain and Spectral Domain Optical Coherence Tomography in Measurement of Macular Thickness in Macular Edema Secondary to Diabetic Retinopathy and Retinal Vein Occlusion 
Journal of Ophthalmology  2012;2012:354783.
Purpose. To evaluate macular thickness, agreement, and intraclass repeatability in three optical coherence tomography (OCT) devices: the time domain (TD) Stratus OCT and two spectral domain (SD) OCTs, Spectralis and Cirrus SD-OCT, in eyes with macular edema secondary to diabetic retinopathy (DR) and retinal vein occlusion (VO). Methods. In a prospective observational study at a university-based retina practice, retinal thickness tomography was performed simultaneously for fifty-eight patients (91 eyes) with DR and VO employing a time domain and two spectral domain OCTs. Agreement in macular measurements was assessed by constructing Bland-Altman plots. Intraclass repeatability was assessed by intraclass correlation coefficients (ICCs). Results. Based on the Bland-Altman plots for central macular thickness, there was low agreement between the measurements of Cirrus SD-OCT and Stratus OCT, Spectralis OCT and Stratus OCT, as well as Spectralis OCT and Cirrus SD-OCT among DR and RVO patients. All three devices demonstrated high intraclass repeatability, with ICC of 98% for Stratus OCT, 97% for Cirrus SD-OCT, and 100% for Spectralis OCT among DR patients. The ICC was 97% for Stratus OCT, 79% for Cirrus SD-OCT, and 91% for Spectralis OCT among RVO patients. Conclusion. There are low agreements among interdevice measurements. However, intraclass repeatability is high in both TD and SD-OCT devices.
doi:10.1155/2012/354783
PMCID: PMC3410350  PMID: 22888403
15.  Hospitalized cardiovascular events in patients with diabetic macular edema 
BMC Ophthalmology  2012;12:11.
Background
Microvascular and macrovascular complications in diabetes stem from chronic hyperglycemia and are thought to have overlapping pathophysiology. The aim of this study was to investigate the incidence rate of hospitalized myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with diabetic macular edema (DME) compared with diabetic patients without retinal diseases.
Methods
This was a retrospective cohort study of a commercially insured population in an administrative claims database. DME subjects (n = 3519) and diabetes controls without retinal disease (n = 10557) were matched by age and gender. Healthcare claims were analyzed for the study period from 1 January 2002 to 31 December 2005. Incidence and adjusted rate ratios of hospitalized MI and CVA events were then calculated.
Results
The adjusted rate ratio for MI was 2.50 (95% CI: 1.83-3.41, p < 0.001) for DME versus diabetes controls. Predictors of MI events were heart disease, history of acute MI, and prior use of antiplatelet or anticoagulant drugs. The adjusted rate ratio for CVA was 1.98 (95% CI: 1.39-2.83, p < 0.001) for DME versus diabetes controls. Predictors of CVA events were cardiac arrhythmia, Charlson comorbidity scores, history of CVA, hyperlipidemia, and other cerebrovascular diseases.
Conclusion
Event rates of MI or CVA were higher in patients with DME than in diabetes controls. This study is one of few with sufficient sample size to accurately estimate the relationship between DME and cardiovascular outcomes.
doi:10.1186/1471-2415-12-11
PMCID: PMC3395554  PMID: 22646811
16.  Aflibercept: a Potent Vascular Endothelial Growth Factor Antagonist for Neovascular Age-Related Macular Degeneration and Other Retinal Vascular Diseases 
Biologics in Therapy  2012;2(1):3.
Introduction
In the western hemisphere, age-related macular degeneration (AMD) is the leading cause of visual loss in the elderly. Currently approved therapies for AMD include argon laser, photodynamic therapy, and antivascular endothelial growth factor (VEGF) therapy. The index review discusses aflibercept (VEGF Trap-Eye) in the context of current anti-VEGF therapies for neovascular AMD and other retinal vascular diseases. It highlights important differences between VEGF Trap-Eye and currently used anti-VEGF therapies for neovascular AMD; and discusses the efficacy of these treatments utilizing information from landmark clinical trials.
Methods
A systematic search of literature was conducted on PubMed, Science Direct, and Scopus with no limitations of language or years of publication.
Results
Preclinical studies have shown that VEGF Trap-Eye binds to VEGF-A with a higher affinity than other anti-VEGF molecules; and that it also binds to placental growth factor (PlGF). In clinical trials, VEGF Trap-Eye has been shown to be as effective in the treatment of neovascular AMD as other anti-VEGF therapies and possibly to have a longer duration of drug activity.
Conclusion
VEGF Trap-Eye has enhanced the treatment options currently available for the management of neovascular AMD. The comparable efficacy of VEGF Trap-Eye (to other anti-VEGF agents) coupled with its longer dosing interval may decrease the number of annual office visits for patients with AMD and their caregivers.
doi:10.1007/s13554-012-0003-4
PMCID: PMC3873045  PMID: 24392297
Aflibercept; Age-related macular degeneration; Antivascular endothelial growth factor; Neovascular age-related macular degeneration; Vascular endothelial growth factor Trap-Eye
17.  Aflibercept: a Potent Vascular Endothelial Growth Factor Antagonist for Neovascular Age-Related Macular Degeneration and Other Retinal Vascular Diseases 
Biologics in Therapy  2012;2(1):3.
Introduction
In the western hemisphere, age-related macular degeneration (AMD) is the leading cause of visual loss in the elderly. Currently approved therapies for AMD include argon laser, photodynamic therapy, and antivascular endothelial growth factor (VEGF) therapy. The index review discusses aflibercept (VEGF Trap-Eye) in the context of current anti-VEGF therapies for neovascular AMD and other retinal vascular diseases. It highlights important differences between VEGF Trap-Eye and currently used anti-VEGF therapies for neovascular AMD; and discusses the efficacy of these treatments utilizing information from landmark clinical trials.
Methods
A systematic search of literature was conducted on PubMed, Science Direct, and Scopus with no limitations of language or years of publication.
Results
Preclinical studies have shown that VEGF Trap-Eye binds to VEGF-A with a higher affinity than other anti-VEGF molecules; and that it also binds to placental growth factor (PlGF). In clinical trials, VEGF Trap-Eye has been shown to be as effective in the treatment of neovascular AMD as other anti-VEGF therapies and possibly to have a longer duration of drug activity.
Conclusion
VEGF Trap-Eye has enhanced the treatment options currently available for the management of neovascular AMD. The comparable efficacy of VEGF Trap-Eye (to other anti-VEGF agents) coupled with its longer dosing interval may decrease the number of annual office visits for patients with AMD and their caregivers.
doi:10.1007/s13554-012-0003-4
PMCID: PMC3873045  PMID: 24392297
Aflibercept; Age-related macular degeneration; Antivascular endothelial growth factor; Neovascular age-related macular degeneration; Vascular endothelial growth factor Trap-Eye
18.  Retinal optical coherence tomography manifestations of intraocular lymphoma 
Purpose
Primary central nervous system lymphoma (PCNSL) is a rare disease. The index report describes a patient with intraocular lymphoma secondary to recurrent PCNSL and corresponding retinal findings on spectral domain optical coherence tomography (SD-OCT).
Methods
Case report.
Results
OCT changes were documented and correlated with the clinical course of intraocular lymphoma progression in the index patient. The OCT changes, manifested as hyperreflective material accumulation in the intraretinal and subretinal pigment epithelial spaces, were caused by lymphomatous infiltration.
Conclusion
SD-OCT can be useful in diagnosing and monitoring the progression or regression of intraocular lymphoma with retinal involvement.
doi:10.1007/s12348-012-0072-z
PMCID: PMC3500988  PMID: 22477623
Spectral Domain Optical Coherence Tomography; SD-OCT; Intraocular lymphoma; Retinal lymphoma
19.  Isolated endogenous Nocardia endophthalmitis after immunosuppression 
Purpose
This study is aimed to report a case of endogenous Nocardia endophthalmitis in the setting of immunosuppression from chronic steroid use.
Methods
A case report was conducted.
Results
A 79-year-old woman presented with decreased vision with floaters in the left eye. Ophthalmic examination revealed severe inflammation in the anterior chamber, vitreous opacities, and retinal detachment. Vitreous cultures grew Nocardia farcinica without any systemic foci of infection found during further workup. The patient was treated with intravitreal amikacin and oral trimethoprim-sulfamethoxazole, and her retinal detachment was later repaired in the operating room. The patient has since remained stable with no signs of retinal detachment or active infection.
Conclusions
Nocardia endophthalmitis is a rare, but serious intraocular infection that should be considered in the differential diagnosis in any immunosuppressed patient, including those receiving steroids, who presents with signs of intraocular infection.
doi:10.1007/s12348-011-0057-3
PMCID: PMC3438302  PMID: 22278699
Endogenous; Endophthalmitis; Nocardia; Immunosuppression; Steroids
20.  Characterization of macular lesions in punctate inner choroidopathy with spectral domain optical coherence tomography 
Purpose
Punctate inner choroidopathy (PIC) is an ocular inflammatory disease. Spectral domain optical coherence tomography (SD-OCT) allows detailed visualization of retinal and choroidal structures. We aimed to describe the retinal changes on SD-OCT associated with PIC lesions localized in the macula.
Methods
Retrospective case series: PIC lesions not associated with choroidal neovascularization (CNV) and captured by macular SD-OCT scans were identified and characterized.
Results
Twenty-seven PIC lesions from seven patients (eight eyes) were identified and classified into four categories according to disease activity and temporal changes. Among clinically inactive patients, two main patterns were noted on OCT: (1) retinal pigment epithelium (RPE) elevation with sub-RPE hyper-reflective signals and (2) localized disruption of outer retinal layers with choroid and Bruch's membrane (BM) generally spared. Clinically active patients demonstrated lesions with intact BM with RPE elevation that fluctuated with disease activity and sub-RPE hyper-reflective signals. Photoreceptor-associated bands on SD-OCT (PRs) were not visible during active disease, but returned to normal visibility when lesions were clinically stable. Seven lesions in patients without clinically detected activity demonstrated alteration of RPE elevation.
Conclusion
SD-OCT can provide detailed structural characteristics of PIC lesions. RPE elevation is noted in many lesions while BM and choroid are spared. Photoreceptor-associated bands on SD-OCT appear compressed during clinically active stages and are visible during stabilization. OCT may provide information on activity not detected clinically.
Electronic supplementary material
The online version of this article (doi:10.1007/s12348-011-0054-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s12348-011-0054-6
PMCID: PMC3438299  PMID: 22210152
Choroid; Optical coherence tomography (OCT); Punctate inner choroidopathy (PIC); Retinal pigment epithelium (RPE)
21.  Macular sensitivity and fixation patterns in normal eyes and eyes with uveitis with and without macular edema 
Purpose
This study aims to investigate the relationship between macular sensitivity and thickness in eyes with uveitic macular edema (UME).
Design
This study is a prospective observational case series.
Methods
The setting for this study was clinical practice. The study included 59 (28 with UME, 31 without UME) eyes of 26 patients with uveitis and 19 eyes of 10 normal subjects. The procedure followed was fundus-related perimetry and retinal thickness map with an automated fundus perimetry/tomography system. Main outcome measures included quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and thickness.
Results
Fixation stability revealed that 56 eyes (93.44%) had stable fixation (>75% within the central 2° of point of fixation); three eyes (6.56%) were relatively unstable (<75% of fixation points located within 2°, >75% located within 4°); and no eye had unstable fixation (<75% of fixation points located within 4°). Evaluation of fixation location revealed that 45 eyes (76.27%) had central fixation location (>50% of fixation point within 0.5 mm of foveal center); seven eyes (11.86%) had peri-central fixation location (25% << 50% within 0.5 mm); and seven eyes (11.86%) had eccentric (<25% of fixation point within 0.5 mm) fixation location. We measured macular sensitivity and corresponding thickness in 1,708 loci of 61 study eyes. Macular sensitivity increased by 0.02 dB (95% confidence interval, 0.00, 0.06) per 1 μm increase in the thickness for the thickness values ≤280 μm. Macular sensitivity decreased by 0.04 dB (95% CI, −0.08, −0.01) per 1 μm increase in the thickness for the thickness values >280 μm.
Conclusions
Perimetry quantification of macular sensitivity and retinal thickness, in association with other factors, may offer novel information regarding the impact of UME on retinal function.
doi:10.1007/s12348-011-0052-8
PMCID: PMC3345050  PMID: 22167465
Uveitis; Uveitic macular edema; Microperimetry; Retinal thickness; Medicine & Public Health; Ophthalmology
23.  Importance of proper diagnosis for management: multifocal choroiditis mimicking ocular histoplasmosis syndrome 
Purpose
The study aims to evaluate a series of patients with initial diagnosis of ocular histoplasmosis syndrome (OHS) with progression and response to treatments consistent with multifocal choroiditis (MFC).
Methods
Retrospective review of nine patients referred for management of recurrent OHS lesions. Serology panel was conducted to rule out autoimmune and infectious causes.
Results
Clinical examination revealed multiple small, punched-out peripheral chorioretinal scars, and peripapillary atrophy. Histoplasma antigen/antibody was negative in all patients. Fluorescein angiography and optical coherence tomography confirmed active inflammation in five patients. Immunomodulatory therapy (IMT) was initiated to control active inflammation. While on IMT, visual acuity stabilized or improved in three patients with no recurrence of CNV or lesion activities over the follow-up period.
Conclusions
MFC may initially masquerade as OHS. Clinical characteristics of recurrent MFC and absence of histoplasma titer may lead to consideration of IMT and other proper treatments for MFC.
doi:10.1007/s12348-010-0016-4
PMCID: PMC3102844  PMID: 21484182
Multifocal choroiditis; Ocular histoplasmosis syndrome
24.  Importance of proper diagnosis for management: multifocal choroiditis mimicking ocular histoplasmosis syndrome 
Purpose
The study aims to evaluate a series of patients with initial diagnosis of ocular histoplasmosis syndrome (OHS) with progression and response to treatments consistent with multifocal choroiditis (MFC).
Methods
Retrospective review of nine patients referred for management of recurrent OHS lesions. Serology panel was conducted to rule out autoimmune and infectious causes.
Results
Clinical examination revealed multiple small, punched-out peripheral chorioretinal scars, and peripapillary atrophy. Histoplasma antigen/antibody was negative in all patients. Fluorescein angiography and optical coherence tomography confirmed active inflammation in five patients. Immunomodulatory therapy (IMT) was initiated to control active inflammation. While on IMT, visual acuity stabilized or improved in three patients with no recurrence of CNV or lesion activities over the follow-up period.
Conclusions
MFC may initially masquerade as OHS. Clinical characteristics of recurrent MFC and absence of histoplasma titer may lead to consideration of IMT and other proper treatments for MFC.
doi:10.1007/s12348-010-0016-4
PMCID: PMC3102844  PMID: 21484182
Multifocal choroiditis; Ocular histoplasmosis syndrome
25.  Retinal Thickness Analysis by Race, Gender, and Age Using Stratus OCT™ 
American journal of ophthalmology  2009;149(3):496-502.e1.
PURPOSE
To detect differences in retinal thickness among patients of different race, gender and age using Stratus OCT™.
DESIGN
Cross-sectional study.
METHODS
In a multicenter, university-based study, 126 patients with no history of ocular disease were enrolled (78 diabetics without retinopathy and 48 nondiabetics). Optical coherence tomography measurements were performed using Stratus OCT™. Statistical comparisons of centerpoint foveal thickness and mean foveal thickness were made using generalized estimating equations adjusting for diabetic status, race, age, and gender.
RESULTS
The study population consisted of 36% males, 39% Caucasians, 33% African Americans, and 28% Hispanics. Mean foveal thickness was 191.6±2.7µm and 194.5±2.7µm for diabetics and nondiabetics, respectively (P=0.49). Mean foveal thickness in males was significantly larger than in females (201.8±2.7µm and 186.9±2.6µm, respectively; P<0.001). Mean foveal thickness was 200.2±2.7µm for Caucasians, 181.0±3.7µm for African Americans, and 194.7±3.9µm for Hispanics. Mean foveal thickness was significantly less for African Americans than Caucasians (P <0.0001) or Hispanics (P=0.005). Centerpoint foveal thickness and mean foveal thickness showed a significant increase with age.
CONCLUSIONS
There are statistically significant differences in retinal thickness between subjects of different race, gender, and age. When compared to Caucasians and Hispanics, African-American race is a predictor of decreased mean foveal thickness; and male sex (regardless of race) is a significant predictor of increased mean foveal thickness. Mean foveal thickness is similar among diabetics and nondiabetics when data are controlled for age, race, and sex. These results suggest that studies comparing OCT measurements should carefully control for age, race, and gender-based variations in retinal thickness.
doi:10.1016/j.ajo.2009.09.025
PMCID: PMC2826608  PMID: 20042179
optical coherence tomography; Stratus OCT™; foveal thickness; age; race; sex

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