Morphometric analysis of the macula in eyes with geographic atrophy due to age-related macular degeneration

PURPOSE: To evaluate the extent of neural cell death in eyes with geographic atrophy (GA). METHODS: Ten eyes with GA and five age-matched control eyes were selected for morphometric analysis. The nuclei of the ganglion cell, inner nuclear, and outer nuclear layers were counted in contiguous 100-microm segments from 1,500 microm nasal to 1,500 microm temporal to the fovea. RESULTS: The outer nuclear layer was most severely attenuated in eyes with GA, demonstrating a 76.9% reduction relative to control eyes (P < 0.0001). A significant loss of ganglion cells (by 30.7%) was also observed (P = 0.0008). There was no significant difference in the inner nuclear layer cells (P = 0.30). Among the GA eyes, the nuclei in all three layers were significantly reduced in segments in which the retinal pigment epithelium was completely absent (P 相似文献   

Symmetry of disciform scars in bilateral age-related macular degeneration.

The size of the final macular scar in subretinal neovascularisation (SRNV) is one of the most important determinants of final visual function in patients with subfoveal disease. We studied patients with bilateral macular scars from age-related subretinal neovascular membranes retrospectively in order to determine whether or not fellow eyes behave similarly. We found a significant correlation between eyes in terms of final scar size (r = 0.50, p less than 0.01). We found that 50% of fellow eyes with large macular scars (greater than 3 x 10(6) microns2) had similar sized lesions, while only 16% of fellow eyes with small macular scars (less than 0.5 x 10(6) microns2) had large scars (p less than 0.01). We discuss the significance of these findings in relation to the pathogenesis of subretinal neovascular membranes, and their implications for treatment.     

Inner retinal layer comparisons of eyes with exudative age-related macular degeneration and eyes with age-related macular degeneration and glaucoma

Background

The incidence of glaucoma increases with age, as does age-related macular degeneration (AMD), with the reported incidence of glaucoma among AMD subjects being 5.4 %. Optical coherence tomography (OCT) can detect glaucomatous changes in the inner retina with high sensitivity. The purpose of this study was to compare ganglion cell complex (GCC) parameters and the thickness of the peripapillary retinal nerve fiber layer (RNFL) in normal eyes to that observed in eyes with age-related macular degeneration (AMD) and eyes with both AMD and glaucoma.

Methods

The GCC components [GCC thickness, focal loss volume (FLV), and global loss volume (GLV)] and peripapillary RNFL thickness were measured using RTVue spectral-domain OCT (SD-OCT). The GCC and RNFL parameters of normal eyes, AMD eyes treated with different types of therapy, and AMD eyes with and without glaucoma were evaluated using nonparametric tests. Univariate and multivariate analyses were used to determine whether the GCC and RNFL parameters could be used to differentiate AMD eyes with glaucoma from those without glaucoma.

Results

Seventy-one normal eyes, 120 eyes with AMD, and 23 eyes with AMD and glaucoma were studied. The values of all GCC components were significantly different in the normal eyes from those observed in the eyes with AMD, except for the RNFL thicknesses. The GCC and RNFL parameters were not significantly different between the eyes receiving different types of therapy among the AMD groups. The RNFL thickness was significantly correlated with glaucoma diagnosis in AMD eyes.

Conclusions

These findings indicate that there is damage to the inner retinal layers in eyes with AMD. The RNFL thickness can be a useful parameter for differentiating eyes with AMD from eyes with both AMD and glaucoma.     

Macular function in eyes with early age-related macular degeneration with or without contralateral late age-related macular degeneration

PURPOSE: To evaluate psychophysical and electrophysiologic responses in eyes with early age-related macular degeneration (AMD) without a decrease in visual acuity and with or without late AMD in the fellow eye. METHODS: Fifteen patients (mean age: 67.9 +/- 7.20 years) with early AMD in both eyes (AMD1 group, 15 eyes) and 15 patients (mean age: 71.40 +/- 7.06 years) with early AMD in one eye and late AMD in the fellow eye (AMD2 group, 15 eyes) were enrolled. They were compared to 15 age-similar normal control subjects. LogMAR visual acuity (VA), macular sensitivity by MP-1 microperimetry, and multifocal electroretinograms (mfERG) were assessed in control, AMD1, and AMD2 eyes. mfERG response amplitude density (RAD, nV/deg2) of the N1-P1 component of first order binary kernels was measured. RESULTS: When compared to controls, AMD1 and AMD2 eyes showed a significant (analysis of variance, P < 0.01) decrease in MP-1 microperimetry assessed in the 0-2.5 and 2.5-5 degrees of the macula, significantly correlated (Pearson test, P < 0.01) to the corresponding significant decrease (P < 0.01) in mfERG N1-P1 RADs assessed in the 0-2.5 and 2.5-5 degrees. In AMD1 and AMD2 eyes, VA and mfERG N1-P1 RADs assessed in the 5-20 degrees were similar (P > 0.01) to controls. VA, MP-1, and mfERG values were not significantly different in AMD1 and AMD2 eyes. CONCLUSION: In eyes with early AMD there is a dysfunction of preganglionic elements in the central 0-5 retinal degrees detectable by mfERG or MP-1 microperimetry. This impairment is not further influenced by the presence of late AMD in the fellow eye.     

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration

PURPOSE: Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. METHODS: Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. RESULTS: A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. CONCLUSIONS: The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.     

Characterization of age-related macular degeneration in Indian donor eyes

Purpose:The purpose of this study was to test the reliability of fundus stereomicroscopy in postmortem eyes to assign severity of age-related macular degeneration (AMD) using the Minnesota grading and confirmation by histology using Alabama and Sarks grading scales and to assess the incidence of AMD pathology in donor eyes from a South Indian population.Methods:Eyes (199) from 153 donors (55–95 years) after obtaining fundus images were processed for histology. Fundus images were graded according to the Minnesota grading system based on drusen size, area of depigmentation, and atrophy. At least one eye from each donor displaying the AMD phenotypes were subjected to histological examination. The fundus grading was correlated with histology and the stages of AMD assigned for early AMD by the Alabama AMD grading system and for both early and advanced AMD by the Sarks classification.Results:Stereoscopic examination of the fundus found that 10 of the 153 donors had features of early AMD and 3 advanced AMD. Following histological examination, one of the early AMD eyes was reclassified as advanced AMD. Early AMD features that were observed on histology included soft drusen (>63 μm), basal laminar deposits, photoreceptor outer segment degeneration, disorganization of retinal pigment epithelium (RPE), Bruch''s membrane thickening. Advanced AMD features observed in histology are extensive atrophy of RPE, choroidal neovascularization and disciform scar formation.Conclusion:Identification of either early or advanced AMD using stereomicroscopic assessment (SMA) showed high sensitivity and specificity. However, misclassification between AMD stages can occur when only SMA is used.     

Morphologic characteristics of disciform scarring after radiation treatment for age-related macular degeneration

OBJECTIVE: To investigate the influence of radiation therapy on the development of disciform lesions in patients with age-related macular degeneration (AMD). DESIGN: A prospective, nonrandomized, comparative trial (patient self-controlled). PARTICIPANTS: Forty eyes with exudative AMD involving the central fovea in 40 consecutive patients were enrolled in this study. INTERVENTION: Radiation was administered to the posterior pole with an 8-mV photon beam from a linear accelerator. A dose of 14.4 Gy, 1.8 Gy per day, five fractions per week was delivered through a single port. MAIN OUTCOME MEASURES: The visual acuity and the morphologic characteristics, demonstrated by fundus photography, fluorescein, and indocyanine green angiography, were investigated before treatment and every 3 months after treatment over a period of 24 months. In 10 patients with bilateral disease the disciform lesions were compared. RESULTS: Twenty five patients could be followed regularly over the period of 24 months. The disciform lesions occurring after radiation were classified in three types. Type I (10 patients) was characterized by being smaller than 2 DD in size, with little fibrotic tissue underneath the retina, but pronounced retinal pigment epithelial changes. Type II (seven patients) showed extensive growth of the choroidal neovascularization (CNV) extending to and beyond the arcades with angiographically active loops in the peripheral parts. Eight patients had type III lesions develop characterized by a size greater than 2 DD but fewer than 6 DD and by a different amount of fibrotic tissue, hemorrhage, and lipid. Type I scarring was significantly associated with occult CNV without pigment epithelial detachments, whereas type II scarring was associated with classic CNV at the initial presentation (P<0.05). CONCLUSIONS: Although no severe side effects have been reported after radiation therapy for AMD, a subgroup of patients may experience extensive growth of CNV after radiation, causing greater functional damage than occurs spontaneously.     

Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration

PURPOSE: To test the hypothesis that neovascular age-related macular degeneration is related to oxidative stress involving the macular retinal pigment epithelium. This study investigated, as a function of age, levels of enzymes that defend tissues against oxidative stress in the macular retinal pigment epithelium of human eyes with this disease. METHODS: Surgical specimens of macular choroidal neovascular membranes from eyes with age-related macular degeneration and the macular regions of whole donor eyes with neovascular age-related macular degeneration or without evident ocular disease were studied by quantitative electron microscopic immunocytochemistry with colloidal gold-labeled second antibodies. Relative levels in retinal pigment epithelium cell cytoplasm and lysosomes were determined of five enzymes believed to protect cells from oxidative stress, as well as levels of the retinal pigment epithelium marker cytoplasmic retinaldehyde-binding protein, for comparison with the enzymes. RESULTS: Copper, zinc superoxide dismutase immunoreactivity increased and catalase immunoreactivity decreased with age in cytoplasm and lysosomes from macular retinal pigment epithelium cells of normal eyes and eyes with age-related macular degeneration. Cytoplasmic retinaldehyde-binding protein immunoreactivity showed no significant relationship to age or the presence of neovascular age-related macular degeneration. Glutathione peroxidase immunoreactivity was absent from human retinal pigment epithelium cells. Both heme oxygenase-1 and heme oxygenase-2 had highly significantly greater immunoreactivity in retinal pigment epithelium cell lysosomes than in cytoplasm, differing from the much greater cytoplasmic immunoreactivity of the other proteins studied. This immunoreactivity decreased with age, particularly in the lysosomes of retinal pigment epithelium cells from eyes with neovascular age-related macular degeneration. These decreases were of borderline significance (P = .067 for heme oxygenase-1; P = .12 for heme oxygenase-2) when eyes with age-related macular degeneration were compared with normal eyes by multivariable logistic regression. CONCLUSIONS: The high heme oxygenase-1 and heme oxygenase-2 lysosomal antigen levels in macular retinal pigment epithelium cells of eyes with neovascular age-related macular degeneration suggest that oxidative stress causes a pathologic upregulation of these enzymes. Increased lysosomal disposal may indicate that the reparative functions of these enzymes are accompanied by deleterious effects, necessitating their rapid removal from the cell. The much higher heme oxygenase-1 and heme oxygenase-2 antigen levels in macular retinal pigment epithelium cells from younger individuals suggest that protective mechanisms against oxidation and, hence, presumably to the development of age-related macular degeneration, decrease with age.     

Development of typical age-related macular degeneration and polypoidal choroidal vasculopathy in fellow eyes of Japanese patients with exudative age-related macular degeneration

PURPOSE: To investigate the development of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in fellow eyes of Japanese patients with exudative AMD. DESIGN: Retrospective observational consecutive case series. METHODS: Two hundred and sixteen Japanese patients were enrolled in this study from the outpatient clinic of the University of Tokyo Hospital. Ninety-one patients had typical AMD and one hundred and twenty-five patients had PCV. The average follow-up period was 33.6 and 25.1 months for typical AMD and PCV patients. RESULTS: The cumulative incidence of involvement in fellow eyes with overall exudative AMD, including both typical AMD and PCV, was 3.4% in one year, 9.3% in three years, and 11.3% in five years. It was 3.6%, 7.3%, and 11.2% in typical AMD, and 3.2%, 11.1%, and 11.1% in PCV in one, three, and five years, respectively. Before the development of exudative AMD, patients with typical AMD had a variety of funduscopic findings including retinal pigment epithelium (RPE) atrophy, drusen, drusenoid pigment epithelial detachments (PED), and normal macula. PCV patients, on the other hand, had funduscopic findings of RPE atrophy. Inner choroidal vascular abnormality of vascular network and polypoidal formation was observed in several eyes before the clinical manifestation of exudative changes. CONCLUSIONS: Typical AMD and PCV had similar probabilities of involving the fellow eye in unilaterally affected Japanese patients. RPE atrophy was a prevailing finding in fellow eyes of patients who developed PCV. In PCV, choroidal vascular network and polypoidal formation gradually grow before exudative changes.     

Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration

Purpose: To measure the concentration of cytokines in the aqueous humour of eyes with exudative age-related macular degeneration (AMD). Methods: The clinical interventional study included a study group of 18 patients with exudative AMD and a control group of 20 patients undergoing routine cataract surgery. Age did not vary significantly (p?=?0.36) between study group (80.8?±?6.4?years) and control group (77.0?±?9.9?years), nor did gender (p?=?0.75). During the interventions, aqueous humour samples were obtained, in which the concentration of cytokines was measured using a solid-phase chemiluminescence immunoassay. Macular thickness was measured by optical coherence tomography (OCT). Results: In the study group as compared to the control group, significantly higher concentrations were measured for epithelial growth factor (EGF) (p?=?0.017), human growth factor (HGF) (p?=?0.048), intercellular adhesion molecule-1 (ICAM1) (p?=?0.028), interleukin 12p40 (IL12p40) (p?=?0.009), interleukin 1a2 (IL1a2) (p?=?0.01), interleukin 3 (IL3) (p?=?0.02), interleukin 6 (IL6) (p?=?0.006), interleukin 8 (IL8) (p?=?0.02), monocyte chemoattractant protein-1 (MCP-1) (p?=?0.048), monokine induced by interferon gamma (MIG) (p?=?0.016), matrix metalloproteinase 9 (MMP9) (p?=?0.004) and plasminogen activator inhibitor 1 (PAI1) (p?=?0.006). Macular thickness was significantly associated with the concentrations of EGF (p?=?0.001), HGF (p?=?0.02), ICAM1 (p?=?0.001), interleukin 12p40 (p?=?0.006), IL 1a2 (p?=?0.002), MIG (p?=?0.001), MMP9 (p?相似文献   

Early deterioration in ellipsoid zone in eyes with non-neovascular age-related macular degeneration

The purpose of this study was to investigate the early effects of soft drusen on retinal pigment epithelium (RPE), ellipsoid zone (EZ, photoreceptor inner segment/outer segment junction), and external limiting membrane (ELM) reflectivities using optical coherence tomography (OCT) image analysis. This retrospective comparative study comprised 47 patients with non-neovascular AMD (with intact RPE, EZ, and ELM bands on OCT) and 45 age- and sex-matched healthy controls with normal OCT. A single masked physician performed OCT image analysis using a medical image processing software. Reflectivities of RPE, EZ, and ELM; number of drusen; vertical and horizontal diameters of the largest druse; druse reflectivity; foveal involvement by a druse; and presence of ≥1 large druse (n) were evaluated based on the macular OCT scan. Forty-seven right eyes of 47 patients with non-neovascular AMD and 45 right eyes of 45 healthy subjects were recruited. In the non-neovascular AMD group, absolute EZ and RPE reflectivities were significantly lower compared to those of the control eyes (P < 0.001 and P = 0.001, respectively). Comparing relative reflectivity values, only relative EZ reflectivity (EZ/ELM reflectivity) remained to show a significant difference between the groups (P < 0.001). Correlation analyses revealed no significant relation between the reflectivity values and drusen characteristics (P > 0.05). In eyes with non-neovascular AMD, decreased RPE (only absolute) and EZ (both absolute and relative) reflectivities prior to the disruption of these layers on OCT might indicate early photoreceptor damage. However, lower reflectivity values appear to be independent of the drusen characteristics.     

Senile disciform macular degeneration and smoking

We studied the smoking habits of 114 patients with senile disciform degeneration of the macula. The mean age at onset of blindness in the first eye was 64 years in those currently smoking; this was significantly less than the mean age in those who had never smoked (71 years). We advise all patients with disciform degeneration to stop smoking.     

Quality of fixation in eyes with neovascular age-related macular degeneration treated with ranibizumab

Aims

To define factors that determine the location and stability of fixation in patients with neovascular age-related macular degeneration (NV-AMD) treated with intravitreal ranibizumab injections.

Methods

The location and stability of fixation using microperimetry were determined in 77 eyes treated with ranibizumab for NV-AMD for at least 12 months. All patients were treated with three injections of ranibizumab 0.5 mg, 1 month apart and retreated according to predefined criteria. The fixation parameters were correlated to the visual acuity, and quantitative measures on OCT.

Results

The location of fixation was predominantly central in 52.6%, poor central fixation in 9.2%, and predominantly eccentric fixation in 38.2%. The fixation was stable in 65%, relatively unstable in 25%, and unstable in 10%. Visual acuity was the only factor that determined the stability and location of fixation. The characteristics of fixation were not related to the macular thickness or volume as measured by OCT.

Conclusions

Better visual outcome ensures central and stable fixation. Quantitative measures of OCT parameters do not determine fixation. Further studies on morphological features of the macula may provide some insight into the determinants of fixation.     

Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment).

In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.