To evaluate the 24-month natural course of visual changes in patients discontinuing treatment despite persistent or recurrent fluid and factors predictive of visual prognosis.
This retrospective, observational study included 35 patients (35 eyes) who initially received anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD), but discontinued treatment despite persistent or recurrent fluid. The best-corrected visual acuity (BCVA) at treatment discontinuation was determined and compared with the 24-month BCVA, which was then compared between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes. Baseline characteristics predictive of visual outcome and the degree of visual change were also analyzed.
The mean number of anti-vascular endothelial growth factor injections before treatment discontinuation was 4.0 ± 1.6. The mean logarithm of minimal angle of resolution of BCVA at treatment discontinuation and that at 24 months were 1.02 ± 0.20 (Snellen equivalents = 20/209) and 1.60 ± 0.56 (20/796), respectively (P , 0.001). The 24-month BCVA was not different between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes (P = 0.803). The type of fluid (intraretinal fluid vs. no intraretinal fluid) was predictive of 24-month BCVA (P = 0.004) and the degree of changes in BCVA (P = 0.043).
Marked deterioration in visual acuity was noted in patients discontinuing treatment, regardless of neovascular age-related macular degeneration subtypes. The presence of intraretinal fluid was associated with worse visual prognosis, suggesting that patients with intraretinal fluid should be strongly warned about their poor prognosis before they decide to discontinue treatment.
Full Paper: Natural Course of Patients Discontinuing Treatment for Age-Related Macular Degeneration and Factors Associated with Visual Prognosis
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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.
“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
“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
Table 1. “Age-Related Macular Degeneration Clinical Trials With Oral Medications”
(Retinalphysician.com | April 2017)
Full Paper: Age-Related Macular Degeneration Clinical Trials With Oral Medications Table
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
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
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
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
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.
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.
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
Age-related Macular Degeneration (AMD) and cataract are common causes of vision loss in our aging population. Recent advances in the treatment of wet AMD have succeeded to either stabilize or improve vision in a large proportion of cases.1–4 It is therefore not uncommon for wet AMD patients to develop visually significant cataracts. However, there is concern about proceeding with cataract surgery in patients with wet AMD, as there may be a risk of exacerbating choroidal neovascularization (CNV) or progressing geographic atrophy.
There is little evidence in the current literature to aid the decision to proceed with cataract surgery in patients undergoing active treatment for wet AMD. Concern exists that intraocular pressure fluctuations and increased inflammatory mediators associated with uncomplicated cataract surgery may disrupt or further stimulate delicate neovascular vessels. Adverse events related to worsening wet AMD may lead to poorer visual outcome or increased AMD treatment demands, requiring further cost and clinic visits for the patient.
Our study aims to evaluate the visual outcomes and possible complications of cataract surgery in patients with wet AMD. This is the first study to include a control arm and an examination of specific optical coherence tomography (OCT) features.
Full Paper: The Effects of Cataract Surgery on Patients With Wet Macular Degeneration
Age-related macular degeneration (AMD) is a complex disorder triggered by a wide range of environmental and genetic risk factors.1-3 Numerous common variants are known markers of AMD including several complement pathway genes: complement factor H (CFH),4-8 complement factor I,9 complement component 2, complement factor B,7,10 and complement 3.11
We previously reported the association of a rare CFH variant with AMD, R1210C, which is the strongest genetic risk factor to date, with an odds ratio (OR) of 20.12,13 The R1210C variant is also known to be associated with inherited forms of atypical hemolytic uremic syndrome and primary glomerulonephritis.14-21 In addition to linking 2 clinically unrelated conditions, such as AMD and atypical hemolytic uremic syndrome,the R1210C finding suggests that compromised function of the factorH protein is involved in AMD pathogenesis as a causal factor and not merely as an associated factor.12
In that initial report, the R1210C rare variant was associated with an earlier age at diagnosis of advanced AMD.12 This variant is also significantly associated with progression from early or intermediate AMD to advanced stages in a multigene prediction model.22,23 However, the fundus phenotype typically related to the variant is still to be determined. This knowledge is needed to better understand the manifestations of this rare CFH mutation and to help detect and characterize this phenotype in clinical practice. Identification of such high-risk individuals will be important for screening, potential new therapeutic strategies, and personalized medicine. Therefore, the objective of this study, conducted from 2012 to 2014, was to determine specific fundus features of a white population carrying the CFH R1210C rare variant.
Full Paper: Phenotypic Characterization of Complement Factor H R1210C Rare Genetic Variant in Age-Related Macular Degeneration
Anti-VEGF therapies in many patients with wet age-related macular degeneration go on to develop atrophy. The speculation for causes of this are:
- Natural progression of underlying age-related macular degeneration driving the atrophy.
- Atrophy is associated with choroidal neovascularization.
- Atrophy is associated with anti-VEGF therapy independent of choroidal neovascularization.
No answers to these theories are yet available, so we should not change how we treat patients. We should, however, advise patients that treating wet age-related macular degeneration may not stop the progression of their underlying dry age-related macular degeneration.