All Posts tagged Study

Macular Degeneration and Aspirin Use

Recent press releases regarding the potential adverse effects of aspirin on macular degeneration have caused patients with age-related macular degeneration (AMD) to discontinue their aspirin use without consulting their physician.1,2 There are many benefits to aspirin use, and therefore many reasons patients should continue taking the recommended aspirin dose prescribed by their primary physician or cardiologists. As with any treatment, it is important to weigh the risk/benefit ratio of aspirin use, especially in generally elderly and high-risk populations. The benefits of aspirin have long been well documented and highly recommended for the prevention and treatment of cardiovascular diseases (CVDs), such as myocardial infarction, stroke, and death. The recent retrospective epidemiological eye studies suggesting that aspirin use may exacerbate macular degeneration are based on three limited studies, while the benefits of aspirin use for macular degeneration patients have been suggested in larger studies, including Age-Related Eye Disease Study (AREDS), the Physicians Health Study (PHS), Women’s Health Study (WHS).1–4 Therefore, the data regarding the effects of aspirin on AMD are conflicting and inconclusive.

Full Paper: Macular Degeneration and Aspirin Use
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YAG Laser Vitreolysis vs Sham YAG Vitreolysis for Symptomatic Vitreous Floaters

Floaters become more prevalent with age because of degenerative vitreous changes that occur throughout life. In youth, hyaluronan keeps collagen fibrils separated in the vitreous cavity and thus maintains transparency of the vitreous. However, with time, hyaluronan dissociates from collagen, causing cross-linking and aggregation of collagen with fibrous structures that scatter light—a process known as vitreous liquefaction.1-3

Clinically, a posterior vitreous detachment (PVD) is often marked by a degree of fibroglial tissue known as a Weiss ring that is free floating over the optic nerve. A PVD allows the vitreous body to move when the head or eye moves, and thus, the Weiss ring and vitreous opacities cast shadows onto the retina that are perceived as floaters.

A PVD is present in approximately 65% of patients reaching the age of 65 years.4,5 Although most patients grow accustomed to the visual disturbance associated with Weiss rings and other floaters, many find them bothersome.6 Floaters can reduce contrast sensitivity and quality of life.7,8

Three management options exist for symptomatic floaters: patient education and observation, pars plana vitrectomywith a 1-incision Intrector (in which a 1-incision, limited core vitrectomy is performed while visualizing through an indirect ophthalmoscope; Insight Instruments) or a standard 3-port vitrector, and YAG vitreolysis.

Existing literature assessing the effect of YAG laser on the properties of rabbit vitreous has suggested that pathologic disruption may occur with laser application in the middle or posterior vitreous.9 There are limited published studies on the effect of YAG vitreolysis for treating symptomatic floaters in humans. Small, uncontrolled cases series6,10,11 assessing YAG vitreolyisis report some symptomatic success and suggest a good safety profile. No prospective, sham-controlled trials have been performed, to our knowledge. This is particularly important because of the subjective nature of floater related visual disturbance and the potential of placebo effect confounding the efficacy of treatment. Research by Karickhoff12 showed the most robust outcomes when treating Weiss rings. Therefore, the current study evaluated YAG vitreolysis in patients with symptomatic Weiss rings.

Full Paper: YAG Laser Vitreolysis vs Sham YAG Vitreolysis for Symptomatic Vitreous Floaters
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Stem Cell Clinics

Recent practices at “stem cell clinics” in the United States have resulted in blinding complications for three patients who underwent bilateral intravitreal injection of adipose-derived stem cell injections for dry age-related macular degeneration, as recently published in the New England Journal of Medicine: patient’s vision went from 20/30 to no light perception and 20/200.

The “stem cell clinics” problem is that they provide unproven, unregulated, and costly ($50,000) treatment for a variety of disorders and raise high concern for patients.

By having studies listed on clinicaltrials.gov, “stem cell clinics” seemingly bolster their legitimacy to patients. clinicaltrials.gov website is simply a repository of clinical studies and does not judge the merits of the listed studies.

It is important to encourage patients to speak with a “trusted healthcare professional” prior to enrolling in a study. Exploring the difference between the positive stem cell research and the activities carried out at “stem cell clinics” is essential in preventing such catastrophic outcomes.

Further regulation of these “stem cell clinics” is also necessary to help prevent similar outcomes in the future.

References

“Implications of Stem Cell Clinics for Retina Patients and Clinical Trials” Retinal Physician, Volume 14, Issue: May 2017, page(s) 32,40: Ajay E. Kuriyan, MD, MS; Thomas Albini, MD; Harry W. Flynn, Jr., MD

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“The Growing ‘Stem Cell Clinic’ Problem” American Journal of Ophthalmology, Volume 177, xix–xx: Ajay E. Kuriyan, MD, MS; Thomas Albini, MD; Harry W. Flynn, Jr., MD

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Retinal Physician Clinical Trial Update

Dry AMD

Study: A Phase 2/3 Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura (Anti-C5 Aptamer) in Subjects With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration

Sponsor: Ophthotech

Purpose: To evaluate the safety and efficacy of intravitreous administration of Zimura when administered in subjects with geographic atrophy (GA) secondary to dry age-related macular degeneration

Design: Randomized, Safety/Efficacy, Parallel Assignment, Double Blind

Number of Patients: 300

Inclusion Criteria: Diagnosis of non-foveal GA secondary to dry AMD

Exclusion Criteria: Retinal atrophy involving the fovea; evidence of CNV; any prior treatment for AMD or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals; any intraocular surgery or thermal laser within 3 months of trial entry; any prior thermal laser in the macular region, regardless of indication; any ocular or periocular infection in the 12 weeks prior to entry; previous therapeutic radiation in the region of the study eye; any sign of diabetic retinopathy in either eye

Full Paper: Retinal Physician Clinical Trial Update
(206K PDF)

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Trends of Anti-Vascular Endothelial Growth Factor Use in Ophthalmology Among Privately Insured and Medicare Advantage Patients

Purpose: To characterize the first 10 years of intravitreal anti-vascular endothelial growth factor (VEGF) medication use for ophthalmic disease, including bevacizumab, ranibizumab, and aflibercept.

Design: A retrospective cohort study using administrative claims data from January 1, 2006 to December 31, 2015.

Subjects: Total of 124 835 patients 18 years of age or over in the United States.

Methods: OptumLabs Data Warehouse, which includes administrative claims data for over 100 million commercially insured and Medicare Advantage individuals, was used to identify patients receiving intravitreal anti-VEGF injections based on Current Procedural Terminology codes.

Main Outcome Measures: Total and annual numbers of intravitreal anti-VEGF injections, as well as injections per 1000 enrolled patients per general category of ophthalmic disease, overall and for each available medication.

Results: There were 959 945 anti-VEGF injections among 124 835 patients from 2006 to 2015. Among all injections, 64.6% were of bevacizumab, 22.0% ranibizumab, and 13.4% aflibercept; 62.7% were performed to treat age-related macular degeneration (AMD), 16.1% to treat diabetic retinal diseases (including 0.9% of all injections that were for proliferative diabetic retinopathy), 8.3% to treat retinal vein occlusions, and 12.9% for all other uses. Use of bevacizumab and ranibizumab for AMD plateaued as of 2011/2012 and decreased thereafter (in 2006, 58.8 and 35.3 injections/1000 AMD patients, respectively; in 2015, 294.4 and 100.7 injections/1000), whereas use of aflibercept increased (1.1 injections/1000 AMD patients in 2011 to 183.0 injections/1000 in 2015). Bevacizumab use increased each year for diabetic retinal disease (2.4 injections/1000 patients with diabetic retinal disease in 2009 to 13.6 per 1000 in 2015) while that of ranibizumab initially increased significantly and then declined after 2014 (0.1 in 2009 to 4.0 in 2015). Aflibercept use increased each year in patients with diabetic etinal diseases and retinal vein occlusions (both >0.1 per 1000 retinal vein occlusion patients in 2011, 5.6 and 140.2 in 2015).

Conclusions: Intravitreal injections of anti-VEGF medications increased annually from 2006 to 2015. Bevacizumab was the most common medication used, despite its lacking U.S. Food and Drug Administration approval to treat ophthalmic disease, and AMD was the most common condition treated. Ranibizumab use declined after 2014 while both the absolute and relative use of bevacizumab and aflibercept increased. Ophthalmology 2017;124:352-358 ª 2016 by the American Academy of Ophthalmology

Full Paper: Trends of Anti-Vascular Endothelial Growth Factor Use in Ophthalmology Among Privately Insured and Medicare Advantage Patients
(599K PDF)

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Retinal Ganglion Cell Layer Change in Patients Treated With Anti–Vascular Endothelial Growth Factor for Neovascular Age-related Macular Degeneration

Age-Related Macular Degeneration (AMD) is one of the leading causes of visual impairment in individuals over the age of 55 years in developed countries.1 The neovascular form of AMD, with vascular endothelial growth factor (VEGF) as one of the key factors, causes severe and irreversible vision loss, frequently resulting in legal blindness.2,3 In recent years, VEGF inhibition by anti-VEGF antibodies has significantly improved visual outcomes in patients with neovascular AMD. However, in many patients with neovascular AMD anti-VEGF needs to be continuously administered over many years to persistently suppress disease activity and maintain visual function.

The need for long-term treatment with anti-VEGF agents has also become evident in the extension studies, where long-term outcomes 7-8 years after initiation of intensive ranibizumab therapy suggest that many patients require long-term treatment with anti-VEGF agents.4 However, despite the beneficial effect of anti-VEGF therapy, long-term side effects are not clarified yet and are a matter of ongoing controversy. There is evidence that repeated long-term anti-VEGF treatment may accelerate atrophy of different ocular tissues. Retinal pigment epithelium atrophy,5 as well as scleral thinning, has been reported.6 In the last years, several studies have investigated the effect of intravitreal anti-VEGF injections on the peripapillary retinal nerve fiber layer (RNFL). There exists some controversy regarding the effect of anti-VEGF agents on retinal ganglion cells (RGCs). In mice, some reports suggest severe damage to RGCs after local treatment with VEGF binding agents,7 while another report did not find any changes within the retinal ganglion cell layer (RGCL) after VEGF receptor blockade in mice.8 Because most studies have analyzed peripapillary optical coherence tomography (OCT) scans, these reports have focused on RNFL change after antiVEGF treatment. However, several studies focusing on glaucoma patients have shown that RGCL thickness changes may be a more sensitive marker for global and regional visual field sensitivities.9,10

In the present study, we investigated RNFL and RGCL changes in the macular area in eyes receiving long-term intravitreal anti-VEGF treatment for neovascular AMD using spectral-domain optical coherence tomography (Spectralis SDOCT; Heidelberg Engineering, Heidelberg, Germany) and automated segmentation of macular scans.

Full Paper: Retinal Ganglion Cell Layer Change in Patients Treated With Anti–Vascular Endothelial Growth Factor for Neovascular Age-related Macular Degeneration
(1.1M PDF)

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The Effect of Postoperative Face-Down Positioning and of Long- versus Short-Acting Gas in Macular Hole Surgery

Macular hole surgery was first described in 1991 by Kelly and Wendel1 and Wendel et al.2 Randomized controlled studies subsequently demonstrated the superiority of surgery over conservative management. These studies used perfluoropropane (C3F8) gas as a tamponade agent, rather than the originally described sulfur hexafluoride (SF6), and advised 2 weeks of face-down positioning (FDP).3-5 The surgical technique has been refined over the past 2 decades.6 Recent studies have demonstrated the additional benefit of internal limiting membrane (ILM) peeling at the time of surgery, and hole closure rates in most recent series are greater than 90%.7-10

There remains broad variability in clinical practice and management of this condition, with no consensus regarding the best surgical approach, particularly regarding the choice of intravitreal tamponade and duration of FDP.11-13 Many investigators have reported good results without FDP.14-25 Various mechanisms of action of the gas tamponade are postulated in macular hole surgery,26 with all assuming that bubble-fovea contact is relevant. Therefore, it would seem intuitive that a larger, longer-acting bubble combined with FDP should be beneficial because this would both facilitate and prolong this apposition. However, there is optical coherence tomography evidence that hole closure occurs very early in the postoperative period, often within the first 24 hours.27-29 As such, longer-acting gases and prolonged (or indeed any) FDP may be unnecessary.

By using a noninferiority study design applied to a large prospective (nonrandomized) registry-based cohort, we aimed to observe whether withholding FDP was noninferior to FDP (of any duration) and whether SF6 gas was noninferior to longer-acting gas tamponades. The present article presents the anatomic outcomes.

Full Paper: The Effect of Postoperative Face-Down Positioning and of Long- versus Short-Acting Gas in Macular Hole Surgery
(1.16M PDF)

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Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration

Importance

There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti–vascular endothelial growth factor (VEGF) injections.

Objective

To evaluate the effect of topical dorzolamide hydrochloride–timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy.

Design, Setting, and Participants

An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit. INTERVENTIONS Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study.

Main Outcomes and Measures

Change in central subfield thicknesswas the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures.

Results

Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μmat enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μmat enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μmat enrollment to 239.9 μmat the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60).

Conclusions and Relevance

These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

Full Paper: Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration
(371K PDF)

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Conversion to Aflibercept After Prior Anti-VEGF Therapy for Persistent Diabetic Macular Edema

Diabetic Macular Edema (DME) is the leading cause of visual impairment in patients with diabetic retinopathy.1 In 2010, approximately 20.6 million out of a projected 92.6 million adults with diabetic retinopathy worldwide were estimated to have concurrent DME.2 This global healthcare burden will likely continue to increase at alarming rates, as some models estimate the number of diabetics will double by the year 2030.3

With the Early Treatment Diabetic Retinopathy Study (ETDRS) in the 1980s,4 macular laser photocoagulation became the mainstay of DME management, and it remained the standard of care in the decades that followed. The advent of intravitreal pharmacotherapy agents, primarily driven by the class of vascular endothelial growth factor (VEGF) inhibitors, has since revolutionized how this condition is treated. Validated through the RISE and RIDE phase 3 clinical trials,5 ranibizumab (Lucentis; Genentech, South San Francisco, California, USA) became the first VEGF inhibitor approved by the Food & Drug Administration (FDA) for this indication in 2012.

While off-label, bevacizumab (Avastin; Genentech) has been evaluated through smaller trials, such as the BOLT study.6 Most recently, aflibercept (Eylea; Regeneron, Tarrytown, New York) gained FDA approval to treat DME in July 2014 with the VIVID and VISTA phase 3 clinical trials.7,8

While there is ample evidence supporting the safety and efficacy of the 3 anti-VEGF agents in the management of DME, a head-to-head comparison only recently became available when the Diabetic Retinopathy Clinical Research Network (DRCR) published the 1-year outcomes of its Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab for DME (Protocol T).9 The results demonstrated that when baseline visual acuity (VA) loss was mild (›20/ 40), there was no clinical difference between the 3 medications. However, when the initial acuity loss was more severe (‹20/50), a greater visual benefit was derived from aflibercept.9

Since the FDA approval of aflibercept for DME, and in light of Protocol T’s findings, many retinal specialists are converting eyes from ranibizumab or bevacizumab to aflibercept with the goal of optimizing treatment outcomes, particularly in cases of refractory DME. In the current study, we evaluated the short-term functional and anatomic responses of patients with persistent DME after multiple previous anti-VEGF injections that were converted to aflibercept therapy.

Full Paper: Conversion to Aflibercept After Prior Anti-VEGF Therapy for Persistent Diabetic Macular Edema
(1.78M PDF)

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Lamellar Macular Hole: Two Distinct Clinical Entities?

Purpose

To investigate whether lamellar macular holes can be divided into different subgroups.

Design

Retrospective observational case series.

Methods

In this institutional study, clinical charts and spectral-domain optical coherence tomography (OCT) images of 102 eyes of 90 consecutive patients diagnosed with lamellar macular hole were reviewed. In OCT imaging, the presence of lamellar macular hole was defined according to the following findings: presence of irregular foveal contour, separation of the layers of the neurosensory retina, and the absence of full-thickness macular defect. Mean outcome was the morphologic and functional characterization of different subtypes of macular hole.

Results

Two different subtypes of lamellar macular hole were identified: tractional and degenerative. The first type, tractional, was diagnosed in 43 eyes, and was characterized by the schitic separation of neurosensory retina between outer plexiform and outer nuclear layers. It often presented with an intact ellipsoid layer and was associated with tractional epiretinal membranes and/or vitreomacular traction. The second type, degenerative, was diagnosed in 48 eyes, and its distinctive traits included the presence of intraretinal cavitation that could affect all retinal layers. It was often associated with nontractional epiretinal proliferation and a retinal “bump.” Moreover, it often presented with early ellipsoidal zone defect and its pathogenesis, although chronic and progressive, remains poorly understood. Eleven eyes shared common features with both tractional and degenerative lamellar macular holes and were classified as mixed lesions.

Conclusions

Degenerative and tractional lamellar macular holes may be 2 distinct clinical entities. A revision of the current concept of lamellar macular holes is needed.

Full Paper: Lamellar Macular Hole: Two Distinct Clinical Entities?
(3.56M PDF)

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