Findings From the 15-Year Follow-up of an Australian Cohort
Early age-related macular degeneration (AMD) is characterized by the presence of drusen and retinal pigmentary abnormalities.1,2 Drusen vary in size (diameter range, ≤63 to ≥250 μm) and type (hard, soft, distinct, and indistinct). Pigmentary abnormalities include clusters of pigment granules within the sensory retina (increased pigmentation) and sharply demarcated areas of retinal pigment epithelium (RPE) depigmentation.
The international classification and grading system for AMD categorizes medium drusen as intermediate soft drusen, defined as drusen with a maximum diameter of 63 to less than 125 μm, larger than the maximum diameter of hard drusen (‹63 μm) but smaller than the minimum diameter of large soft drusen (≥ 125 μm).1 A similar definition of this drusen type was used by the Age-Related Eye Disease Study2 and clinical classification system,3 categorized as medium drusen. urthermore, the Wisconsin Age-Related Maculopathy Grading System4 defines medium drusen by the maximum diameter, although the categorization of medium drusen is not used. In this study, we describe this type of drusen as medium drusen.
Despite recent interest in medium drusen and their inclusion in AMD incidence studies,5,6 knowledge of the associated risk factors and the progression of medium drusen is limited. Medium drusen have been underrepresented in studies3,7-9 compared with large drusen, soft drusen, and pigmentary lesions. In this study, we aimed to assess the 15-year incidence and progression of medium drusen in an older Australian cohort, as well as associations between common AMD risk factors and the development and progression of medium drusen.
Full Paper: Incidence, Progression, and Associated Risk Factors of Medium Drusen in Age-Related Macular Degeneration
The role of the vitreomacular interface (VMI) in the pathophysiologic features and treatment of neovascular age-related macular degeneration (AMD) has generated much recent interest. In retrospective and prospective observational case series, a higher prevalence of vitreomacular adhesion (VMA) has been reported in eyes with neovascular AMD compared with eyes with nonneovascular AMD.1-3 In a paired eye study, VMA was observed more frequently in eyes with neovascular AMD compared with the fellow nonneovascular AMD eye that served as a control.4 Some investigators also have observed that VMA occurs at the vitreoretinal interface overlying the choroidal neovascularization (CNV).1,2,4 Vitreomacular adhesion also influences treatment and outcomes in neovascular AMD; the absence of VMA has been associated with slightly better visual acuity (VA),5,6 and eyes with VMA may require more frequent dosing compared with neovascular AMD eyes without VMA.5,6 This combined body of evidence suggests thatVMA may have a role in the pathogenesis and management of CNV.
The purpose of our study was to assess the relationship of the VMI to treatment frequency in neovascular AMD, as well as to VA and anatomic outcomes in the Comparison of AMD Treatments Trials (CATT),7 one of the largest prospective treatment trials for neovascular AMD conducted to date.
Full Paper: Influence of the Vitreomacular Interface on Treatment Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials
AGE-RELATED MACULAR DEGENERATION (AMD) IS the leading cause of late-onset visual impairment and blindness in persons over 65 years of age.1,2 Age-related macular degeneration is staged as early, intermediate, or late. Small drusen are the hallmark of earlystage AMD; intermediate-stage AMD consists of extensive medium-size drusen or any large drusen, with or without pigment changes. Late-stage AMD is defined by either choroidal neovascularization or geographic atrophy.3–6 In the United States, it is estimated that ~1.2 million persons have neovascular AMD; 970,000 have geographic atrophy; and 8 million have intermediate-stage AMD.1
Antiretroviral-treated, immune-restored, human immunodeficiency virus (HIV)-infected persons have a marked reduction in opportunistic infections and a substantially increased lifespan compared to those from the era before modern combination antiretroviral therapy.7–10 However, despite the improved immune function and increased lifespan, antiretroviral therapy does not fully restore health. Compared to similarly-aged, non-HIV-infected peers, antiretroviral-treated, immune-restored, HIV-infected persons have a substantially shortened lifespan, largely owing to an increased risk of non–acquired immunodeficiency syndrome (AIDS) diseases associated with aging.11–14 These diseases include cardiovascular disease, non-AIDS cancers, metabolic diseases, and neurocognitive decline, and collectively suggest that antiretroviral-treated, immune-restored HIV infection is associated with an “accelerated/accentuated aging” phenotype.11 Therefore, we undertook to evaluate whether persons with AIDS had an increased prevalence of AMD, using retinal photographs taken at enrollment in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort.
Full Paper: Prevalence of Intermediate-Stage Age-Related Macular Degeneration in Patients With Acquired Immunodeficiency Syndrome
Age-related macular degeneration is a very common condition that is caused by a complex interplay of genetic and environmental factors. It is likely that, in the future, genetic testing will allow physicians to achieve better clinical outcomes by administering specific treatments to patients based on their genotypes. However, improved outcomes for genotyped patients have not yet been demonstrated in a prospective clinical trial, and as a result, the costs and risks of routine genetic testing currently outweigh the benefits for patients with age-related macular degeneration.
Full Paper: Genetic Testing for Age-Related Macular Degeneration Not Indicated Now
Robert E. MacLaren from Oxford, England has published an article in The Lancet, January 2014, describing the results of six patients who received gene therapy for choroideremia.
The initial results of the retinal gene therapy showed improved rod and cone function. In all patients over six months, there was an increase in retinal sensitivity in the treated eyes that correlated with the vector dose of the gene therapy.
The study assessed the effects of an adeno-associated virus (AAV) vector encoding REP1 (AAV.REP1) in patients with choroideremia. Choroideremia is an x-linked recessive disease that causes blindness due to mutations in the CHM gene, which encodes the Rab escort protein 1 (REP1).
The findings warrant further assessment of gene therapy in choroideremia, age-related macular degeneration, retinitis pigmentosa, and Stargardt’s disease.
A Japanese government panel Wednesday June 25, 2013 approved the world’s first clinical research using iPS cells. Massayo Takahoshi, M.D., Ph.d will serve as head of the clinical study in Kobe Japan.
Six patients with wet AMD will have skin cells taken and genetically reprogrammed to become iPS cells. These cells will be modulated to grow into RPE cells which will take 10 months. The sheets of the RPE cells will then be transplanted into the eyes under the retina of patients who have had abnormal blood vessels removed.
These patients will then be monitored over the next four years to determine how well the implants have performed and whether the body has accepted them.
We will all benefit from the information obtained about minimizing tumorigensis from the induced genetic mutations and possible viral contamination regardless of what level of efficacy is attained.
We were acknowledged by the Foundation for Fighting Blindness for our effort in one of six emerging retinal therapies receiving foundation funding as part of its Translational Research Acceleration Program (TRAP). The emerging treatments included those using stem cells, gene therapies, and pharmaceuticals.
Multilayered Cell Replacement Therapy
Many retinal diseases, including Stargardt disease, dry age-related macular degeneration, and choroideremia, lead to loss of photoreceptors and a supportive layer of cells called retina pigment epithelium (RPE). Dr. David Gamm of the University of Wisconsin is using induced pluripotent stem cells (iPSC) to develop a two-layered cell replacement therapy.
To minimize rejection of this and other treatments, he is also developing lines of iPSC from “super donors,” individuals from across the United States whose immune profiles favorably math those of the country’s general population. For these efforts, Dr. Gamm is collaborating with scientists from: University of California, Santa Barbara; University of Pennsylvania; Cellular Dynamics International; and Retina Vitreous Resource Center in Louisville, Kentucky.
You are following a patient with successful treatment of a subretinal neovascular membrane from any of the following disorders:
Or edema secondary to:
If this patient were to suddenly develop any of the following signs or symptoms or findings on OCT, this may justify a re-referral to the initial treating retinal subspecialist.
Signs and Symptoms
- Decreased central visual acuity.
- Complaints of blurred central vision.
- Rubeosis on the iris.
- Hazy vision of recent onset.
- Patient states their vision is cloudy.
- Hemorrhaging in the fovea on clinical retinal examination.
- An OCT finding of retinal thickening at or within 500 units of the center of the macula.
- An OCT finding of hard exudate at or within 500 units of the center of the macula if associated with adjacent retinal thickening.
- An OCT finding of a zone or zones of retinal thickening one disc-area in size, at least part of which is with one disc-diameter of the center of the macula.
- Increased central retinal thickness on OCT.
- Subretinal fluid over large contiguous drusen in the fovea on OCT.
A phone call to the retinal subspecialist may suffice or he/she may feel examining the patient is in order.
Sustained Increased Intraocular Pressure Related to Intravitreal Antivascular Endothelial Growth Factor Therapy for Neovascular Age-related Macular Degeneration
The following article, Sustained Increased Intraocular Pressure Related to Intravitreal Antivascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration (J. Glaucoma; Volume 21, Number 4, April/May 2012), makes note of increased intraocular pressure following anti-VEGF drug therapy that we have noted in our practice as well. It appears that after seven (7) shots, there is an increased risk of patients developing sustained elevated intraocular presure, which they have never experienced in the past. The second observation is that it appears patients with an open capsule have an increased risk over patients with intact capsules for this sustained increased intraocular pressure. Most patients respond well to medical therapy with eye drops over time as the pressure goes down, but a few may proceed on to require filtering bleb surgery.
Proposed etiologies for the elevated pressure have been looked for. Researchers began looking for microscopic particulate contaminates. It has been thought that the molecular weight of the drugs may play a role in a blockage of the trabecular meshwork as well as some people thinking that the lubricant primarily used in tuberculin syringes was the culprit. This is the reason that many compounding pharmacies no longer send their drugs in tuperculin syringes.
At this point, the definite etiology for the pressure rise is unknow but is under continued investigation. It is important to note that this is a secondary complication with Avastin, Lucentis, and Eylea therapy that is just now coming to the forefront.
If we can answer any of your questions regarding this form of therapy, please feel free to let us know.
The Preliminary CATT (Comparison of AMD Treatment Trials) results are in and they support the use of either Avastin or Lucentis for the treatment of neovascular AMD. The May 2011 edition of the New England Journal of Medicine contained an editorial written by Philip J. Rosenfeld, M.D., Ph.D. which stated, “The CATT data support the continued global use of intravitreal bevacizumab as an effective, low-cost alternative to ranibizumab.”