It also emphasizes the importance of at-home monitoring. Simply put, the sooner the better. Recommending healthy diet, exercise, smoking cessation and UV protection is generally a positive thing for any patient, but especially those with risk factors such as family history of AMD, systemic vascular disease, poor nutrition and history of smoking.
Discuss with them how such factors increase risk of macular degeneration and how lifestyle modifications can decrease it. Give your patients a reference sheet of AMD lifestyle modifications such as this one. Smoking remains the most important modifiable risk factor for development and progression of AMD.
Making dietary recommendations can be daunting for those who are not used to this type of conversation. Even simple recommendations can spark a change for patients. One easy recommendation for patients can be to eat more naturally sourced food.
Real, whole, unprocessed foods with a focus on brightly colored fruits and vegetables is a good place to start. Additional suggestions may include observing a Mediterranean-type diet that involves intake of fatty fish rich in omega-3 oils at least twice per week and incorporating whole grain forms of rice, pasta and bread.
Educate patients on the correlation between AMD and a sedentary lifestyle, obesity and vascular diseases such as hypertension, diabetes and hyperlipidemia. Nutritional supplementation remains controversial. So, unfortunately, there is not an easy or straightforward answer. For a disease with no cure and very limited treatment options, there is a desire to do everything possible for a patient.
This has to be appropriately balanced with current evidence. Recommendations for vitamin supplementation must always consider potential adverse effects alongside potential benefits. There is no evidence to support the use of these supplements for patients who have less than intermediate AMD and no evidence of any prophylactic value for family members without signs of AMD.
Soft drusen are the width of a major retinal vein as it crosses the disc black arrow. I am going to recommend a supplement for you. This does not take the place of a healthy diet and lifestyle that involves wearing sunglasses and discontinuing smoking, which are equally important! What about those with early AMD or at-risk patients? While there is no substantial proof that vitamin supplementation reduces the risk of AMD progression or development in those with early-stage disease or at-risk patients such as those whose family members have AMD, there are multiple trials that suggest benefit to macular pigment optical density as well as both objective and subjective measures of visual function including visual acuity, contrast sensitivity and electroretinography with various types of vitamin supplementation.
Supplementation with carotenoids such as lutein, zeaxanthin and meso-zeaxanthin seems reasonable in this patient population, particularly in those with poor nutrition or visual limitations such as difficulty seeing at night. A suggested follow-up and management depending on the stage of disease is shown in Table 1. It has been well documented that patients with any large-sized drusen nm or larger or with pigmentary changes on clinical exam are at increased risk for conversion to advanced AMD.
This is approximately the width of a major retinal vein as it crosses the disc margin Figure 6a. It is highly important to make this distinction for three reasons. Second, this is also when to use an at-home monitoring system. Third, it is pertinent to educate these patients and monitor them more carefully due to their increased risk of developing advanced AMD. OCT imaging can be useful in visualizing small- to large-sized drusen and getting a sense of the size of the drusen deposits.
In addition, it can help to detect a particular high-risk phenotypical variant of drusen deposition called reticular pseudodrusen RPD , also known as subretinal drusenoid deposits. This variation is difficult to distinguish clinically and presents as small- to intermediate-sized drusen. Although small in size, patients with these deposits are even more likely than patients with large-sized drusen to develop advanced AMD.
Also, these patients tend to be more symptomatic with worse visual function than other AMD phenotypes. Optometrists often have the training, the knowledge and the access to all the tools necessary to manage patients with non-exudative AMD. Proper patient education, appropriate lifestyle, nutritional and nutraceutical recommendations, identification of risk factors and emphasis of both in-office and at-home monitoring can all lead to better visual outcomes for our patients with AMD.
The neurogenic potential of MC was first identified in a chicken retina [ ] and thereafter in a rodent retina [ ]. There is also evidence that MC from the primate retina can become progenitor-like cells in vitro [ ] but the potential of these glial cells to regenerate neurons in an intact primate retina remains unexplored. In addition, mammalian MC can respond to injury, proliferate, and express genes associated with retinal stem cells but they do not function as retinal progenitors in vivo [ , ].
Nonetheless, these characteristics suggest that, under the right conditions, MC might be induced to adopt the characteristics of a retinal progenitor that could be used for retinal neuron repair. Indeed, MC cell culture from humans has the capacity to generate both neurons and glial cells [ , ] suggesting that human MC are capable of generating neurons under appropriate conditions and they could be able to participate in retinal repair and could be used for AMD treatment.
Experimental data showed the expression of neurogenic genes, such as Notch and Wnt, in MG culture that induce photoreceptor progenitors [ ].
On the other hand, activation of FGF, Notch, Wnt, and Sonic-hedgehog signaling events induces a significant number of MC cells to reenter the cell cycle and display properties of retinal progenitors in the injured mammalian retina [ — ].
These results indicate that some part of the regenerative cellular program may be induced for retinal repair in patients with retinal degeneration, suggesting that overexpression of Achaete-Scute complex-like 1 Ascl1 in MC culture induces a neurogenic state of MC, proliferation, and bipolar neuron generation.
This has led to propose Ascl1 as a potential target for neurodegenerative therapy after disease or injury [ ]. Apparently, microglia lack the neurogenic capacity observed in macroglia stimulated in vitro [ ]. Nevertheless, it seems that activation of microglial reactivity is an important step in stimulating MC to dedifferentiate, proliferate, and become progenitor-like. It is likely that reactive microglia provide signals to modulate the reentry into the cell cycle [ ].
Alternatively, the reactive microglia could suppress inhibitory signals that prevent the formation of MG progenitor-like cells [ ]. The identity of the signals provided by reactive microglia to stimulate the formation of progenitor-like MG remains uncertain, but the participation of proinflammatory cytokines and components of the complement system is possible [ ]. Another important factor for the neurogenic potential of MG might be the age of the organisms.
Experimental studies have shown that MG from the mouse retina ex vivo express neurogenic factors and generate progeny expressing neuronal and glial markers in response to growth factor stimulation; nevertheless, the potential regenerative capacity of MG becomes limited with increasing mouse age [ ]. Emerging evidence suggests that MG are dormant stem-like cells found throughout the retina and serve as a source of progenitor cells to regenerate retinal neurons after injury, although barriers to regenerative cell survival, migration, integration, and safety concerns remain to overcome.
Endogenous retinal repair is progressing rapidly, and the turn of the endogenous stem cells approach into viable therapy might be soon. In the past decades, stem cell-based research has become a very promising area in biology. It has been acknowledged that terminally differentiated cells can be successfully reprogrammed [ , ]. Furthermore, both systemic and local stem cell-based therapies have been used in various diseases with positive results.
While the wet AMD could be treated and fairly controlled by the use of drugs that target the VEGF receptor, the application of laser photocoagulation, and vitrectomy, among other surgical procedures, the dry AMD commonly demonstrates poor outcomes with conventional therapeutic approaches.
Damage in dry AMD is mostly attributed to the accumulation of reactive oxygen species and peroxide, in addition to chronic inflammation in the retina that leads to apoptosis of the retinal pigment epithelial RPE cells, which gradually damage the photoreceptors [ , ].
Autologous RPE transplantation as an alternative surgical approach has been extensively studied, generally performed by collecting the healthy RPE in the peripheral retina and transplanting them into the subretinal space at the diseased macula [ , ]. Fully functional RPE cells can be generated from stem cells or somatic cells by spontaneous differentiation or cell reprogramming [ ]. Takahashi and Yamanaka and Yu et al.
In addition, in a study by Carr et al. Similarly, Vaajasaari et al. However, there are several advantages to the use of progeny obtained from hESCs as a source of replacement tissue for clinical studies Figure 2 a [ ]. These include in vitro differentiation that can be controlled to ensure optimum safety, purity, and potency before transplantation into the selected population of patients [ , ].
The first data obtained from two of these clinical trials reported no signs of rejection, evident hyperproliferation, or tumorigenesis [ ]. Moreover, Schwartz et al. Conversely, stem cell generation may present challenges as well. Abnormal gene expression has been reported in some iPSCs, in which the T-cell-mediated immune response can be elicited even in syngeneic hosts [ ].
In addition, another pending challenge would be the immunosenescence, a process that results in the progressive decline of the fine control in the immune system, including the loss of the CD28 receptor, increased interleukin production, and an increase in the IL-6 receptor. All of these changes could not only annul the immune privilege but could also create an environment appropriate for cell death [ , ]. Stem cell-based therapies have been the object of an extensive research, and great advances have recently been made towards the generation of stem cell transplantation techniques for the functional replacement of RPE cells and photoreceptors.
Adverse events related to the surgery have to be further studied, and large numbers of patients with microperimetry assessments in conjunction with optical coherence tomography OCT and autofluorescence estimation should be evaluated to provide more rigorous structure-function correlations. Recent promising developments in the functional replacement of retinal RPE cells give rise to the expectation that clinical replacement of damaged retinal cells may be able to improve the outcomes of patients with retinal degenerative disease in the near future.
As we have seen, there are many factors that influence the origin and progression of AMD and the more relevant pathways associated with chronic retinal degeneration. This opens new windows to provide multiple therapeutic targets for disease treatment. However, the design of new treatments must be very carefully done because most of the altered pathways in AMD are broadly redundant and may induce negative effects. Therefore, the new treatments should be carefully designed to cover different altered mechanisms at the same time.
Looking towards the future of AMD therapy, there is an emerging paradigm that diverges from the normal approach of preventing retinal dysfunction and death. We should try to recover retinal health in spite of injury, rather than avoid and eliminate numerous overlapping insults.
This kind of research should not be discarded in order to improve AMD prevention and treatment. Some experimental ideas are already being performed in our laboratory.
Finally, it is totally necessary to consider the financial burden that AMD represents due to its progressive nature, for example, loss of productivity, and related expenses like nursing homes, caretakers, and comorbidities, and currently available treatment is a significant challenge to any health system.
Currently, it represents an excessive direct annual medical cost and, as the incidence raises with the passing of time, the annual cost will increase; for this reason, the finding of a new functional treatment for AMD becomes totally needful.
The funding organization had no role in the review design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors state that they have full control of all primary data. The authors thank Ann H. Milam Ph. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors.
Read the winning articles. Journal overview. Special Issues. Academic Editor: Kai Kaarniranta. Received 29 Jul Accepted 06 Dec Published 01 Feb Abstract Age-related macular degeneration AMD is a well-characterized and extensively studied disease.
Introduction The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss Figure 1. Figure 1. The RPE orange is thinned over drusen. Cell nuclei are blue DAPI. Figure 2. Early AMD involves the accumulation of drusen and beta-amyloid peptides in the subretinal space. This might progress to dry AMD a , which is characterized by inflammation and photoreceptor degeneration, caused in part by oxidative stress; resveratrol and alpha-lipoic acid prevent these effects.
Autophagy induction by trehalose might help to eliminate intracellular components that abnormally accumulate intracellularly avoiding the following extracellular accumulation of toxic peptides, like beta-amyloid and lipids. Additionally, ranibizumab, aflibercept, bevacizumab, and bevasiranib could be used to block the angiogenic effects of VEGF on both cases. References R. Velez-Montoya, S. Oliver, J. Olson, S. Fine, N. Mandava, and H. Salvi, S. Akhtar, and Z. Ashraf and A.
Fine, H. Jarrett and M. Whitcup, A. Sodhi, J. Atkinson et al. Marneros, J. Fan, Y. Yokoyama et al. Olsson, A. Dimberg, J. Kreuger, and L. Koch, S. Tugues, X. Li, L. Gualandi, and L. Byeon, S. Lee, S. Choi et al. Gu, G. Ke, L. Wang et al. Uno, I. Bhutto, D. McLeod, C. Merges, and G. Bhutto, K. Uno, C. Merges, L.
Zhang, D. McLeod, and G. Kauppinen, J. Paterno, J. Blasiak, A. Salminen, and K. Garba and S. Kleinman, K. Yamada, A. Takeda et al. Alghisi and C. Dong, B. Xie, J. Shen et al. Dentchev, A. Milam, V. Lee, J. Trojanowski, and J. View at: Google Scholar J. Hollyfield, V. Bonilha, M. Rayborn et al.
Shaw, T. Stiles, C. Douglas et al. S14—S22, Iacovelli, G. Rowe, A. Khadka et al. Schmidl, G. Garhofer, and L.
Leach, G. Van Tuyle, P. Lin, R. Schmidt-Ullrich, and R. View at: Google Scholar Y. Chen, J. Zeng, C. Zhao et al. Saitoh, A. Miyanishi, H. Mizuno et al. Chan, C. He or she may also do several other tests, including:.
Our caring team of Mayo Clinic experts can help you with your dry macular degeneration-related health concerns Start Here.
As of now, there's no treatment for dry macular degeneration. However, there are many clinical trials in progress. If your condition is diagnosed early, you can take steps to help slow its progression, such as taking vitamin supplements, eating healthfully and not smoking.
Age-related macular degeneration doesn't affect your side peripheral vision and usually doesn't cause total blindness. But it can reduce or eliminate your central vision — which is necessary for driving an automobile, reading and recognizing people's faces. It may be beneficial for you to work with a low vision rehabilitation specialist, occupational therapist, your eye doctor and others trained in low vision rehabilitation.
They can help you find ways to adapt to your changing vision. For selected people with advanced dry macular degeneration in both eyes, one option to improve vision may be surgery to implant a telescopic lens in one eye. The telescopic lens, which looks like a tiny plastic tube, is equipped with lenses that magnify your field of vision.
The telescopic lens implant may improve both distance and close-up vision, but it has a very narrow field of view. It can be particularly useful in an urban environment to aid in identifying street signs. Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.
Even after receiving a diagnosis of dry macular degeneration, you can take steps that may help slow vision loss. Choose a healthy diet. The antioxidant vitamins in fruits and vegetables contribute to eye health. Kale, spinach, broccoli, squash and other vegetables have high levels of antioxidants, including lutein and zeaxanthin, which may benefit people with macular degeneration. Foods containing high levels of zinc also may be of particular value in patients with macular degeneration.
These include high-protein foods, such as beef, pork and lamb. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity.
Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation. Abstract Age-related macular degeneration AMD , the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology.
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