Imagen en retromodo para el diagnóstico de drusas del disco óptico: una serie de casos / Retro-mode imaging for the diagnosis of optic disc drusen: A case series

Objetivo: Nuestro principal objetivo es el de comparar la capacidad para detectar las drusas del disco óptico (DDO) utilizando diversas técnicas de imágenes no-invasivas, incluida la novedosa técnica de imagen de retromodo (RMI). Como segundo objetivo analizamos las características morfológicas de las DDO bajo esta última técnica. Materiales y métodos: Este estudio incluyó un total de 7 pacientes con DDO bilaterales, obteniendo un total de 14 ojos analizados. Se utilizaron técnicas no invasivas de imágenes multimodales, que incluyeron fotografía multicolor del fondo de ojo (MC), reflectancia en infrarrojo (NIR), autofluorescencia en luz verde y en luz azul (G-FAF y B-FAF, respectivamente) y RMI. La FAF se utilizó como el método principal para el diagnóstico de DDO. Dos observadores realizaron las comparaciones, obteniendo las tasas de detección de cada uno de los métodos. Las mediciones cuantitativas de las DDO incluyeron el número, el perímetro (P) y el área (A) de las DDO identificadas mediante la técnica de RMI. Resultado: La edad promedio de los pacientes incluidos fue de 49,28±23,16 años; 5 de los 7 pacientes fueron de sexo masculino. La técnica de RMI pudo detectar DDO en todos los casos, con una sensibilidad del 100%, en comparación con MC (sensibilidad del 60,71%), NIR (sensibilidad del 60,71%), B-FAF (sensibilidad del 100%), G-FAF (sensibilidad del 100%). RMI fue la única técnica de imagen capaz de evaluar morfológica y cuantitativamente las DDO. Conclusiones: RMI es una prometedora modalidad no-invasiva de imagen para diagnosticar DDO superficiales, proporcionando información valiosa sobre la distribución, la ubicación y el tamaño de estas. Por lo tanto, mediante nuestros resultados sugerimos la incorporación de la novedosa técnica de RMI como una herramienta complementaria para el diagnóstico y el seguimiento de DDO en combinación con los otros métodos de imagen multimodales.(AU)

Objective: We aimed to compare the detectability of optic disc drusen (ODD), using various non-invasive imaging techniques, including the novel retro-mode imaging (RMI), as well as to analyze the morphological characteristics of ODD on RMI. Methods: This study involved 7 patients with bilateral ODD, totaling 14 eyes. Multimodal imaging techniques, including multicolor fundus photography (MC), near-infrared reflectance (NIR), green and blue light fundus autofluorescence (G-FAF and B-FAF, respectively), and RMI were used to examine the eyes. FAF was used as the primary method of identifying ODD, and each method's detection rate was compared by two observers. Quantitative measurements of ODD included the number of ODD visualized by the RMI technique, the perimeter (P) and area (A) of ODD were identified. Results: The average age of the patients included was 49.28±23.16 years, with 5 of the 7 being men. RMI was able to detect ODD in all cases, with a sensitivity of 100%, compared to MC (sensitivity 60.71%), NIR (sensitivity 60.71%), B-FAF (sensitivity 100%), G-FAF (sensitivity 100%). RMI was the only imaging technique capable of assessing ODD morphology and quantifying ODD. Conclusions: RMI is a promising imaging modality for diagnosing superficial ODD, providing valuable information on the distribution, location, and size of ODD. We suggest the incorporation of RMI as a complementary tool for diagnosing and monitoring ODD in combination with other multimodal imaging methods.(AU)

Therapeutic Management and New Upcoming Approaches for Age Related Macular Degeneration.

Age-related Macular Degeneration (AMD) is a severe eye illness that is going to lead in the race for incurable blindness globally among the elderly population. AMD is the third common reason responsible for affecting the quality of life globally. The macula and the retinal layers are adversely affected during AMD and are responsible for the loss of vision eventually. Numerous genetic variables, lipid metabolism, ageing and oxidative damage are the causative factors in the genesis of AMD. Lack of antioxidants, smoking and excessive alcohol intake contribute to increasing the risk of AMD. Management of dry AMD involves the use of nutritional supplements like zinc and antioxidants, along with conventional treatment, however, the use of nutritional supplements can only give minor benefits on the progression of dry AMD. Later stages of AMD need to be managed by cell-based interventions where the damaged or lost cells are replaced with fresh donor cells. A plethora of treatment methods are used in the management of AMD, such as nutrition, antibody-based treatments, stem cell management and nanotherapeutics. The available expensive treatments come with a number of adverse effects and future developments require the involvement of risk factor modification approaches, personalized therapy, targeting the disease specific pathways, exploring better anti-vascular endothelial growth factor (VEGF) inhibitors and many other regenerative approaches, that will broaden techniques to diagnose, control and treat AMD. This review provides an overview of the progression of AMD and the causative factors, with considerable emphasises on the current and potential prospects.

A unique case of bilateral nanophthalmos and pigmentary retinal abnormality with unilateral angle closure glaucoma and optic disc pit.

BACKGROUND: Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative anterior microphthalmos, and posterior microphthalmos based on the anterior segment: posterior segment ratio. Nanophthalmos can occur in association with optic disc drusen, foveoschisis, and retinitis pigmentosa, as an autosomal recessive syndrome linked to mutations in the MFRP gene. We report a case of bilateral nanophthalmos and pigmentary retinopathy with angle closure glaucoma and optic disc pit in one eye. We believe this to be the first case presenting with optic disc pit in association with nanophthalmos. CASE PRESENTATION: A 56-year-old female presented with bilateral small eyes, high hypermetropia, shallow anterior chamber depth, increased lens thickness, mid-peripheral retinal flecks, and macular edema. She also had high intraocular pressure in the right eye, with a disc cupping of 0.9 with an Optic disc pit. The macular edema in the right eye was found to occur in association with the Optic disc pit, whereas, in the left eye, it was associated with intra-retinal hemorrhages and diagnosed as macular branch retinal vein occlusion secondary to hypertension. She was started on anti-glaucoma medications in both eyes and planned for Anti-VEGF injection in the left eye. CONCLUSION: This case report is unique as it reports an association of Nanophthalmos with Optic Disc pit, with an associated angle closure glaucoma in the same eye, an association which has never been previously reported in the literature.

Adherence of patients with age-related macular degeneration to AREDS 2-recommended nutritional supplements.

BACKGROUND: The Age-Related Eye Disease Study 2 (AREDS 2) proved the benefit of vitamin and mineral supplementation in preventing advanced age-related macular degeneration (AMD). AREDS 2 supplements are indicated for patients with either bilateral intermediate AMD (AREDS category 3) or unilateral neovascular AMD (AREDS category 4). AIMS: The aims of this telephone survey were to identify the rate of adherence of patients to AREDS 2 supplements and the factors associated with non-compliance in these patient groups. METHODS: A patient telephone survey was conducted in an Irish tertiary care hospital. Patients were identified by chart review, and their AREDS categorization was reconfirmed. A telephone consultation was conducted with each patient to assess their compliance with the micronutrient supplements. RESULTS: We identified 120 patients who met the AREDS criteria for supplementation. Of these, 103 patients were graded as category 4, and 17 patients were graded as category 3. Almost a fifth (18%) were current smokers. Under two-thirds (60%) of the patients were taking AREDS 2 supplements. Of the remainder, 83% of patients did not recall being advised of their benefit. The cost was cited by 10% of patients as a reason for non-compliance. CONCLUSION: The ophthalmologist not only has a duty of care to treat the neovascular complications of AMD, but they must also strive to improve patient compliance with AREDS supplements. The cessation of smoking needs to be actively promoted in order to stop preventable vision loss in patients with AMD.

[The potential of physiotherapy technologies in the rehabilitation of patients with non-exudative form of age-related macular degeneration (drusen)]. / Vozmozhnosti primeneniya fizioterapevticheskikh tekhnologii v oftal'moreabilitatsii patsientov s neekssudativnoi formoi vozrastnoi makulyarnoi degeneratsii (druzy).

Age-related macular degeneration (AMD) is currently the leading cause of vision loss in the elderly population worldwide. Despite the experience of using physiotherapeutic methods of treatment for non-exudative form of age-related macular degeneration, as well as the lack of clear criteria for its indication and evaluation of its effectiveness, the question of its advisability remains open. PURPOSE: Evaluation of the effectiveness of rehabilitation complex involving physiotherapy in the form of infrared and magnetic stimulation of the retina, aerogenation with Heliox21 and dry needling in patients with non-exudative AMD (drusen). MATERIAL AND METHODS: The study included 84 patients (168 eyes), among them 50 men and 74 women with stage 1 non-exudative AMD, aged 60 to 70 years old (average age 60±3.7 years), who were divided into 2 groups with comparable clinical and functional characteristics. Group 1 included 42 patients (84 eyes) who underwent ophthalmic neurostimulation consisting of daily infrared-magnetic stimulation of the retina for 10 days, 10 procedures of daily aerogenation with Heliox21 and 10 daily procedures of acupuncture. Group 2 included 42 patients (84 eyes) who received only basic parenteral therapy (Nutrof forte 1 tablet per day during the entire observation period), which was also the medication background in the main group. Visual acuity (VA), retinal OCT parameters, local photosensitivity and bioelectrical potential indices were assessed with mfERG. The control time points were before therapy, after 2 weeks, 3 months, 6 months and 12 months. RESULTS: After undergoing therapy with the described physiotherapeutic regimen, a positive effect on functional characteristics was noted - the level of light sensitivity of the central zone of the retina and the amplitude of the electrical biopotential have improved. The indicators of maximally corrected visual acuity and the structure of the ellipsoidal zone of the retina and the choroid did not change during the entire observation period. CONCLUSION: In patients with non-exudative form of AMD the developed ophthalmic rehabilitation complex involving infrared-magnetic stimulation of the retina, aerogenation with Heliox21 and dry needling promotes improvement of functional characteristics of the central retina in the form of increased maximal light sensitivity of the central retinal area and increased amplitude of bio-electrical potential.

Complete Resolution of Central Soft Drusen without Geographic Atrophy or Choroidal Neovascularization.

The treatment and prevention of dry age-related macular degeneration (AMD) traditionally involve lifestyle modifications and antioxidant supplementation, including the AREDS2 formula. We present a case of a woman with dry AMD in her right eye with several large, confluent central drusen on her exam and optical coherence tomography B-scan. Over the course of a year, the drusen almost completely disappeared, but the retinal layers were preserved without the development of geographic atrophy or choroidal neovascularization. While the exact cause of this phenomenon is unclear, it was thought to be associated with this patient's strict daily use of numerous dietary supplements. This case highlights the potential in exploring alternative medicine supplements in the treatment of AMD.

Research advances of modern and traditional medicine on dry age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

@#Age-related macular degeneration(ARMD)is one of the main causes of irreversible visual impairment in the middle-aged and elderly people, which severely impacts the patient's life quality and poses a substantial health economic burden on society. There are two types of late ARMD in clinic: wet ARMD and dry ARMD. Anti-vascular endothelial growth factor drugs, as first-line clinical drugs for wet ARMD, achieved remarkable efficacy. For dry ARMD, however, effective therapies are in the air. This review focuses on the potential drugs, biological therapies and traditional Chinese medicines that made significant progresses in clinical trials for dry ARMD, including anti-inflammatory drugs(doxycycline and FHTR2163), anti-oxidants(risuteganib and elamipretide), complement inhibitors(APL-2 and zimura), visual cycle modulators(ALK-001), neuroprotective agents(brimonidine), stem cell transplantation(MA09-hRPE and BMMF), gene therapy(HMR59), and traditional Chinese medicine(saffron, curcumin, quercetin and resveratrol). The new drugs exhibited favorable clinical efficacy and broad application prospects, which would foster hope for improvement and treatment of ARMD.

[Pharmacological and physiotherapeutic methods of treating non-exudative age-related macular degeneration]. / Farmakologicheskie i fizioterapevticheskie metody lecheniya neekssudativnoi formy vozrastnoi makulyarnoi degeneratsii.

The non-exudative form of age-related macular degeneration (AMD) is a disease with long-term progression for which effective treatments have not been found. Many studies are being conducted to find effective drugs to prevent the appearance of drusen and increase in RPE atrophy area, which could help avoid this more dangerous form of AMD. The main drugs (nutraceuticals) that are used to treat the dry form of AMD are lutein, zeaxanthin and omega-3 fatty acids. Additionally, treatment may include nanosecond laser therapy for drusen in advanced AMD, panretinal subthreshold micropulse laser exposure for atrophic AMD, as well as microcurrent stimulation. Further research in this area should be aimed at understanding all the pathogenetic mechanisms associated with the development of AMD, and developing new approaches to the treatment of this disease including physiotherapy.

Effects of Zinc Acetate Hydrate Treatment on Serum Oxidative Stress Markers in Patients with Macular Drusen.

Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 µg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P = 0.03). The serum zinc level was significantly correlated with the MDA level (P = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 µmm2, P = 0.04). Conclusions: The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.

Pharmacologic activation of autophagy without direct mTOR inhibition as a therapeutic strategy for treating dry macular degeneration.

Dry age-related macular degeneration (AMD) is marked by the accumulation of extracellular and intracellular lipid-rich deposits within and around the retinal pigment epithelium (RPE). Inducing autophagy, a conserved, intracellular degradative pathway, is a potential treatment strategy to prevent disease by clearing these deposits. However, mTOR inhibition, the major mechanism for inducing autophagy, disrupts core RPE functions. Here, we screened autophagy inducers that do not directly inhibit mTOR for their potential as an AMD therapeutic in primary human RPE culture. Only two out of more than thirty autophagy inducers tested reliably increased autophagy flux in RPE, emphasizing that autophagy induction mechanistically differs across distinct tissues. In contrast to mTOR inhibitors, these compounds preserved RPE health, and one inducer, the FDA-approved compound flubendazole (FLBZ), reduced the secretion of apolipoprotein that contributes to extracellular deposits termed drusen. Simultaneously, FLBZ increased production of the lipid-degradation product ß-hydroxybutyrate, which is used by photoreceptor cells as an energy source. FLBZ also reduced the accumulation of intracellular deposits, termed lipofuscin, and alleviated lipofuscin-induced cellular senescence and tight-junction disruption. FLBZ triggered compaction of lipofuscin-like granules into a potentially less toxic form. Thus, induction of RPE autophagy without direct mTOR inhibition is a promising therapeutic approach for dry AMD.

Dietary Nutrient Intake and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2.

PURPOSE: To analyze associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration (AMD), its subtypes, and large drusen. DESIGN: Post hoc analysis of 2 controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2. PARTICIPANTS: Eyes with no late AMD at baseline among AREDS participants (n = 4504) and AREDS2 participants (n = 3738) totaled 14 135 eyes. Mean age was 71.0 years (standard deviation, 6.7 years), and 56.5% of patients were women. METHODS: Fundus photographs were collected at annual study visits and graded centrally for late AMD. Dietary intake of multiple nutrients was calculated from food frequency questionnaires. MAIN OUTCOME MEASURES: Progression to late AMD, geographic atrophy (GA), neovascular AMD, and (separate analyses) large drusen. RESULTS: Over median follow-up of 10.2 years, of the 14 135 eyes, 32.7% progressed to late AMD. For 9 nutrients, intake quintiles 4 or 5 (vs. 1) were associated significantly (P ≤ 0.0005) with decreased risk of late AMD: vitamin A, vitamin B6, vitamin C, folate, ß-carotene, lutein and zeaxanthin, magnesium, copper, and alcohol. For 3 nutrients, quintiles 4 or 5 were associated significantly with increased risk: saturated fatty acid, monounsaturated fatty acid, and oleic acid. Similar results were observed for GA. Regarding neovascular AMD, 9 nutrients were associated nominally with decreased risk-vitamin A, vitamin B6, ß-carotene, lutein and zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid, and alcohol-and 3 nutrients were associated with increased risk-saturated fatty acid, monounsaturated fatty acid, and oleic acid. In separate analyses (n = 5399 eyes of 3164 AREDS participants), 12 nutrients were associated nominally with decreased risk of large drusen. CONCLUSIONS: Higher dietary intake of multiple nutrients, including minerals, vitamins, and carotenoids, is associated with decreased risk of progression to late AMD. These associations are stronger for GA than for neovascular AMD. The same nutrients also tend to show protective associations against large drusen development. Strong genetic interactions exist for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. These data may justify further research into underlying mechanisms and randomized trials of supplementation.

The neurobiology of nutraceuticals combined with light exposure, a case report in the course of retinal degeneration.

The present article presents a case report and discusses the neurobiology underlying the potential neuro-repair induced by combined administration of phytochemicals in a patient undergoing photo-bio-modulation (PBM), which improves anatomical and clinical abnormalities in the course of age-related macular degeneration (AMD). After combined treatments the patient with nutraceuticals and PBM had noticeable improvement of retinal tissue with excellent vision for her age and no worsening of corneal guttae, which was present at the time of diagnosis. The present treatment was tailored, based on translational evidence, to improve the autophagy pathway, which is a key determinant in the onset and progression of AMD. In fact, treatment with specific patterns of light exposure combined with specific phytochemicals, may synergize in improving the microanatomy of the retina by restoring its neurobiology. The combination of light exposure, at selective wavelengths, with the effects produced by the intake of specific phytochemicals to treat AMD is reported here as "Lugano Protocol". Such a clinical protocol represents an "in progress" development backed up by translational research. In fact, recent evidence indicates that, specific phytochemicals, when administered in combination may promote anatomical and functional integrity within the retina. These in turn synergize with analogous effects produced by specific wavelengths, when administered at specific time intervals. The synergism between specific light and combined phytochemicals is discussed at molecular level, where recent data indicate how these treatments, when delivered according to specific patterns, may enhance autophagy in the retina. The improvement of retinal morphology and visual acuity, observed in this case report is thoroughly discussed in the light of the key role of autophagy in regulating the integrity of the retinal epithelium. Despite exciting, and consistent with translational evidence, the clinical report of a disease modifying effect during AMD owns the inherent limit of a case report, which requires wide validation in large number of patients. The potential effectiveness of "Lugano protocol" may apply to other types of retinal degenerations, where common alterations in the autophagy pathway do occur. Thus, such a therapeutic approach may extend to a common late stage of retinal trans-synaptic degeneration, where maladaptive plasticity during several types of retinal degenerative disorders eventually converge.

The Effect of Lycium barbarum Polysaccharides on Pyroptosis-Associated Amyloid ß1-40 Oligomers-Induced Adult Retinal Pigment Epithelium 19 Cell Damage.

Age-related macular degeneration (AMD) is a sight-threatening disease with limited treatment options. We investigated whether amyloid ß1-40 (Aß1-40) could cause pyroptosis and evaluated the effects of Lycium barbarum polysaccharides (LBP) on Aß1-40 oligomers-induced retinal pigment epithelium 19 (ARPE-19) damage, which is an in vitro AMD model. Aß1-40 oligomers verified by Western blot were added to ARPE-19 cells with or without 24 h LBP treatment. Aß1-40 oligomers significantly decreased ARPE-19 cell viability with obvious morphological changes under light microscopy. SEM revealed swollen cells with a bubbling appearance and ruptured cell membrane, which are morphological characteristics of pyroptosis. ELISA results showed increased expression of IL-1ß and IL-18, which are the final products of pyroptosis. LBP administration for 24 h had no toxic effects on ARPE-19 cells and improved cell viability and morphology while disrupting Aß1-40 oligomerization in a dose-dependent manner. Furthermore, Aß1-40 oligomers up-regulated the cellular immunoreactivity of pyroptosis markers including NOD-like receptors protein 3 (NLRP3), caspase-1, and membrane N-terminal cleavage product of GSDMD (GSDMD-N), which could be reversed by LBP treatment. Taken together, this study showed that LBP effectively protects the Aß1-40 oligomers-induced pyroptotic ARPE-19 cell damages by its anti-Aß1-40 oligomerization properties and its anti-pyroptotic effects.

Hemorragia peripapilar subretinal profunda como complicación asociada a drusen de nervio óptico / Deep subretinal peripapillary bleeding as a complication associated to optic nerve drusen

RESUMEN Los drusen de nervio óptico fueron descritos por primera vez por Liebreich en el año 1868. Otros términos para designar esta entidad incluyen cuerpos hialinos y cuerpos coloides del disco óptico. Tienen una prevalencia de 1 por 500 y el 60 por ciento de los casos se encuentran profundos en la cabeza del nervio óptico. La patogenia primaria de los drusen puede ser una displasia hereditaria del canal óptico del disco óptico y su vasculatura, lo que predispone a la formación de estos. La evolución natural de los drusen es un proceso dinámico que transcurre durante toda la vida. Entre las complicaciones asociadas se presentan defectos de campo visual, pérdida de visión central (rara pero bien documentada), neuropatía óptica isquémica, oclusiones vasculares retinales, pérdidas transitorias de la visión, neovascularización subretinal peripapilar, corioretinopatia serosa central peripapilar y hemorragias pre y peripapilares. Se presenta una paciente de 64 años de edad con antecedente de haber sido operada de desprendimiento de retina del ojo izquierdo, y en el ojo derecho presentaba una hemorragia peripapilar subretinal profunda asociada a drusen(AU)

ABSTRACT Optic nerve drusens were first described by Liebreich in the year 1868. Other terms to designate this condition are optic disc hyaline bodies and colloid bodies. They have a prevalence of 1 per 500 and 60 percent of the cases occur deep in the optic nerve head. The primary pathogenesis of drusens may be an inherited dysplasia of the optic canal of the disc and its vasculature, which leads to their formation. The natural evolution of drusens is a lifelong dynamic process. Associated complications include visual field defects, central vision loss (rare but well documented), ischemic optic neuropathy, retinal vascular occlusion, transient sight loss, peripapillary subretinal neovascularization, central serous peripapillary chorioretinopathy, and pre- and peripapillary bleeding. A case is reported of a 64-year-old female patient with a history of surgery for retinal detachment of the left eye. In the right eye the patient presented deep peripapillary subretinal bleeding associated to drusen(AU)

Unstimulated, Serum-free Cultures of Retinal Pigment Epithelium Excrete Large Mounds of Drusen-like Deposits.

Purpose: A hallmark of age-related macular degeneration is the accumulation of deposits of lipids and proteins, called drusen, in Bruch's membrane. Several culture models of retinal pigment epithelia (RPE) develop drusen-like deposits. We examined whether prolonged culture of RPE with a retina-like tissue affected the number or size of these deposits. Methods: RPE and retinal progenitor cells (RPC) were differentiated from induced pluripotent stem cells derived from fetal tissue and maintained in serum-free medium containing the B27 supplement. RPE was cultured on Transwell filter inserts, and RPC were cultured on a planar matrix composed of gelatin, hyaluronic acid, and chondroitin sulfate. After seeding the filter, RPC were layered on top of the RPE. RPE ± RPC were cultured for six months. The function of RPE tight junctions was assessed by the transepithelial electrical resistance. Cultures were stained for actin, neutral lipids, APOE, TIMP3, vitronectin, and calcium deposits. Morphometric analysis was used to determine the number and volume of the "druse". Results: After six months, the TER was greater for the co-cultures (304 ± 11 Ω× cm2 vs 243 ± 7 Ω× cm2, p < .01). RPE formed mounds of druse-like deposits that contained, vitronectin, APOE, TIMP3 and calcium deposits, but lipids were undetected. The mounds overlay areas of the filter where no lipid was detected in the pores, and the RPE overlying the mounds was often thin. The number of "druse"/100,000 µm2 was 5.0 ± 0.4 (co-cultures) vs 2.3 ± 0.1 (monocultures) (p < .05). The total volume of "drusen"/100,000 µm3 was 15,133 ± 1544 (co-cultures) vs 5,993 ± 872 (monocultures) (p < .05). There was no statistical difference between the size-distribution of druse-like particles formed by each culture. Conclusions: Covering the apical membrane of RPE with a thick tissue increased the number of druse-like deposits. The apparent size limitation of the deposits may reflect the apparent interruption of the of lipid cycle found at the basal membrane of the RPE.

On the origin of proteins in human drusen: The meet, greet and stick hypothesis.

Retinal drusen formation is not only a clinical hallmark for the development of age-related macular degeneration (AMD) but also for other disorders, such as Alzheimer's disease and renal diseases. The initiation and growth of drusen is poorly understood. Attention has focused on lipids and minerals, but relatively little is known about the origin of drusen-associated proteins and how they are retained in the space between the basal lamina of the retinal pigment epithelium and the inner collagenous layer space (sub-RPE-BL space). While some authors suggested that drusen proteins are mainly derived from cellular debris from processed photoreceptor outer segments and the RPE, others suggest a choroidal cell or blood origin. Here, we reviewed and supplemented the existing literature on the molecular composition of the retina/choroid complex, to gain a more complete understanding of the sources of proteins in drusen. These "drusenomics" studies showed that a considerable proportion of currently identified drusen proteins is uniquely originating from the blood. A smaller, but still large fraction of drusen proteins comes from both blood and/or RPE. Only a small proportion of drusen proteins is uniquely derived from the photoreceptors or choroid. We next evaluated how drusen components may "meet, greet and stick" to each other and/or to structures like hydroxyapatite spherules to form macroscopic deposits in the sub-RPE-BL space. Finally, we discuss implications of our findings with respect to the previously proposed homology between drusenogenesis in AMD and plaque formation in atherosclerosis.

Long-term Results of Taking Anti-oxidant Nutritional Supplement in Intermediate Age-related Macular Degeneration

PURPOSE: We prospectively investigated clinical changes and long-term outcomes after administration of the drugs recommended by the Age-Related Eye Disease Study-2 to patients with intermediate age-related macular degeneration (AMD). METHODS: This prospective multicenter study enrolled 79 eyes of 55 patients taking lutein and zeaxanthin. The primary endpoint was contrast sensitivity; this was checked every 12 months for a total of 36 months after treatment commenced. The secondary endpoints were visual acuity, central macular thickness, and drusen volume; the latter two parameters were assessed using spectral domain optical coherence tomography. RESULTS: The mean patient age was 72.46 ± 7.16 years. Contrast sensitivity gradually improved at both three and six cycles per degree. The corrected visual acuity was 0.13 ± 0.14 logMAR and did not change significantly over the 36 months. Neither the central macular thickness nor drusen volume changed significantly. CONCLUSIONS: Contrast sensitivity markedly improved after treatment, improving vision and patient satisfaction. Visual acuity, central retinal thickness, and drusen volume did not deteriorate. Therefore, progression of AMD and visual function deterioration were halted.

Research advances in therapy of dry age-related macular degeneration / 眼科新进展

Age-related macular degeneration(AMD) is the major cause of irreversible damage to vision in over 60 years old.Its incidence is increasing with age.Dry AMD is one of the most common types,causing the loss of vision is very slow.At the late stage,the geographic atrophy will be found,in which central vision is severely lost.It is widely believed that chronic inflammantion injury,oxidative stress injury,lipofuscin,drusen and choroid ischemia are the major pathogenesis.Now,the treatment is major aiming to the pathogenesis.But some new therapies such as crocetin,curcumin,ciliary neurotrophic factor,nanoceria,human monoclonal antibody,photoreceptor and stem cell transplantation have some efficiency to dry AMD.This article reviews the research advances in therapy of dry AMD.

Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment.

IMPORTANCE: Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. OBJECTIVE: We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD. DESIGN: Pilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80 mg of atorvastatin daily and were monitored at baseline and every 3 months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women). RESULTS: Twenty-three subjects completed a minimum follow-up of 12 months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+ 3.3 letters, p = 0.06) in 10 patients. No subjects progressed to advanced neovascular AMD. CONCLUSIONS: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.