Age-related macular degeneration: a complementopathy?

Age-related macular degeneration (AMD) is a progressive eye disease affecting many elderly individuals. It has a multifactorial pathogenesis and is associated with numerous environmental (e.g. smoking, light and nutrition) and genetic risk factors. A breakthrough in the mechanisms causing AMD is emerging; the involvement of the alternative pathway of the complement system appears to play a pivotal role. This has led to the statement that AMD is a disease caused by a hyperactive complement system, allowing the term 'complementopathy' to define it more precisely. Abundant evidence includes: the identification of drusen components as activators of complement, immunohistochemical data showing the presence of many species of the complement system in the retinal pigment epithelium-Bruch's membrane-choroidocapillary region of AMD eyes, a strong association of AMD with certain genetic complement protein variants, raised complement levels in blood from AMD patients and the preliminary successful treatments of geographic atrophy with complement factor D (FD) inhibitors. FD is the rate-limiting enzyme of the alternative complement pathway, and is produced by adipose tissue. Recent findings suggest that nutrition may play a role in controlling the level of FD in the circulation. Addressing modifiable risk factors such as smoking and nutrition may thus offer opportunities for the prevention of AMD

Treatment of negative dysphotopsia with supplementary implantation of a sulcus-fixated intraocular lens

PURPOSE: Our aim was to evaluate the resolution of negative dysphotopsia supplementary implantation of a sulcus-fixated intraocular lens (IOL). This was a retrospective case series. Patients with severe negative were treated with supplementary implantation of the Rayner Sulcoflex (653 L) IOL. Primary outcome measurements were subjectively reported of dysphotopsia, best corrected distance visual acuity (CDVA), iris-IOL anterior chamber depth (ACD) and volume (ACV), angle opening distance trabecular-iris space area at 500 and 750 mum. RESULTS: A Rayner was implanted in seven patients (nine eyes) with negative dysphotopsias. resolved completely in six eyes, partially in one eye and remained two eyes. We did not find any significant changes in CDVA. Angle opening distance, ACD, ACV and iris-IOL distance reduced significantly after IOL implantation. CONCLUSIONS: Supplementary implantation of a Sulcoflex successfully treat negative dysphotopsia. The decrease in anterior dimensions in combination with the displacement of light rays by the edges of a Sulcoflex IOL may contribute to the resolution of symptoms

Long-term plant stanol and sterol ester-enriched functional food consumption, serum lutein/zeaxanthin concentration and macular pigment optical density.

Observational epidemiological studies have shown that low carotenoid intake and/or low carotenoid blood levels increase the risk of degenerative diseases like age-related macular degeneration. Functional foods enriched with plant sterol or stanol esters may lower serum concentrations of fat-soluble carotenoids. Theoretically, as a result the macular pigment optical density (MPOD), a marker for eye health, may change. We carried out a double-blind placebo-controlled human intervention trial with a duration of 18 months to evaluate the possible effects of plant stanol and sterol esters on serum lutein/zeaxanthin concentration in relation to the MPOD. Forty-seven subjects were randomly assigned to one of the three treatment groups: margarine without added plant sterols or stanols, plant sterol-enriched margarine, or plant stanol-enriched margarine. Serum cholesterol and lutein/zeaxanthine concentrations and the MPOD were evaluated at baseline and at study end. Changes in lipid-adjusted serum lutein/zeaxanthine concentrations between baseline and study end differed significantly between the three groups (P = 0.001). We found no differences in the MPOD between the three treatment groups, despite the differences in both absolute and cholesterol-standardized serum lutein/zeaxanthine concentrations. This shows that the observed reduction in serum carotenoid concentrations during 18 months consumption of these functional foods does not affect MPOD

Value of preoperative phakic intraocular lens simulation using optical coherence tomography

PURPOSE: To compare the position of the iris-fixated phakic intraocular lens (pIOL) in preoperative simulation and after implantation using anterior segment optical coherence tomography (AS-OCT). SETTING: Department of Ophthalmology, Academic Hospital Maastricht, Maastricht, The Netherlands. METHODS: In this prospective study, the morphometrics of the anterior chamber were analyzed using preoperative pIOL simulation and postoperative images assessed with AS-OCT. Patients' eyes were examined before and 6 months after pIOL implantation. The measured distances were from the center of the pIOL to the endothelium, from the edge of the pIOL to the endothelium (nasal and temporal side), and from the back of the pIOL to the crystalline lens. RESULTS: Thirty-four eyes (18 patients) were examined. All morphometric parameters showed highly significant correlations and small mean differences between preoperative and postoperative measurements. However, the distance from the nasal edge of the pIOL to the endothelium and the distance from the pIOL to the crystalline lens showed a statistically significant difference between the preoperative simulation and the actual postoperative measurements (P = .045 and P = .001, respectively). The ranges of agreement between all preoperative simulations and postoperative measurements ranged between 0.24 mm and 0.29 mm. CONCLUSIONS: Preoperative simulation was a useful additional tool in the selection of patients considering pIOL implantation and in ensuring the long-term safety of pIOLs. However, clinicians should be aware of the range between the preoperative simulation and the postoperative measurements

The effect of modified eggs and an egg-yolk based beverage on serum lutein and zeaxanthin concentrations and macular pigment optical density: results from a randomized trial

Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements

Macular pigment optical density relates to foveal thickness

PURPOSE: Macular pigment is composed of 2 dietary carotenoids, lutein and zeaxanthin, and is mainly present at the nerve fiber layers and ganglion cell layers of the retina, with peak concentrations in the fovea. It is thought to function as a blue-light filter and antioxidant, and therefore protect the retina from damaging influences that are thought to play a role in the pathogenesis of age-related macular degeneration. This study was performed to investigate the suggested positive relationship between foveal macular pigment optical density (MPOD) and foveal retinal thickness. METHODS: We determined MPOD and foveal thickness in the right eyes of 40 healthy Caucasian subjects (5 men, 35 women) recruited at the University of Maastricht, The Netherlands. Their mean age was 24.4+/-8.7 years. MPOD was determined by using a novel method of heterochromatic flicker photometry (HFP), where subjects have to detect flicker instead of conventionally minimizing a present flicker motion. Foveal thickness parameters were obtained using optical coherence tomography (OCT 3). RESULTS: We found a positively significant correlation between MPOD and central foveal thickness (r=0.359, p=0.027). In addition, we found a negatively significant correlation between foveal thickness and foveal width (r= -0.558, p<0.001). CONCLUSIONS: Our data confirm the previously suggested positively significant correlation between MPOD and central foveal thickness. The observed negative relationship between foveal thickness and foveal width may be explained by eccentric scans on the OCT

Analysis of visual pigment by fundus autofluorescence.

Contains fulltext : 69802.pdf (publisher's version ) (Closed access)This study investigated changes of short-wavelength fundus autofluorescence (SW-AF) by retinal bleaching effects. All measurements were performed with the Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done on a healthy eye after dark adaptation. Photopigment was bleached within the central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of this region was performed, and SW-AF of the surrounding, unbleached 25 degrees fundus region was subsequently studied by a wide-field lens. Next, another 30 degrees SW-AF image of the posterior pole was obtained after complete dark adaptation. Then an extra SW-AF examination was performed with 15 degrees temporal eccentricity, overlapping the original examination area. Finally, a successive image series was carried out on the dark-adapted eye to test for bleaching kinetics. The second and third experiments were also performed on eyes with macular dystrophies. Distinct regions of increased SW-AF were observed after strong illumination with the blue excitation light in all eyes studied. During light adaptation mean gray levels showed a saturation plateau after an initial steep increase. The resulting gray-value maps showed significant differences of pixel intensities between bleached and unbleached parts of the fundus. Two-dimensional density difference maps allowed analysis of visual pigment distribution and density in both healthy eyes and eyes with macular dystrophies. Our observations highlight the viability of objective, non-invasive evaluation of visual pigment in the healthy and diseased human retina by means of confocal fundus autofluorescence

VERY EARLY DISEASE MANIFESTATIONS OF MACULAR TELANGIECTASIA TYPE 2

BACKGROUND: To report very early morphologic and functional alterations in patients with macular telangiectasia type 2. METHODS: Patients with asymmetric disease manifestations, in whom retinal alterations characteristic for macular telangiectasia type 2 were present in one but not in the apparently unaffected fellow eye, underwent multimodal imaging and functional testing (microperimetry, visual acuity, reading ability, Amsler test). RESULTS: Fellow eyes not allowing the diagnosis of macular telangiectasia type 2 based on hitherto diagnostic standards consistently showed a severely reduced directional cone reflectance (Stiles-Crawford effect). Optical coherence tomography revealed an asymmetric configuration of the foveal pit with focal temporal thinning most pronounced at 1 degrees eccentricity. Topographically related, macular pigment optical density was reduced in a small wedge-shaped temporal paracentral sector, resulting in an increased signal on fundus autofluorescence and fluorescein angiography imaging. No functional deficits were detectable in fellow eyes. Haidinger brushes were perceived in the fellow eye but not in the affected index eye with pronounced loss of macular pigment. CONCLUSION: Specific morphologic alterations precede vascular alterations and functional deficits in macular telangiectasia type 2. The described alterations indicate a primarily degenerative process with a secondary retinal vascular phenotype, and may be helpful for early identification of patients and affected family members

Use of Anterior Segment Optical Coherence Tomography to Study Corneal Changes after Collagen Cross-linking

PURPOSE: To investigate the stromal demarcation line after corneal cross-linking using anterior segment optical coherence tomography (AS-OCT) and its influence on the short-term results of cross-linking in patients with progressive keratoconus. DESIGN: Prospective, nonrandomized study. METHODS: Twenty-nine eyes of 29 patients with progressive keratoconus (n = 28) or after laser in situ keratomileusis ectasia (n = 1) were included and treated with corneal cross-linking at our institution. Measurements at 1, 3, 6, and 12 months after corneal cross-linking were: refraction, best-corrected visual acuity (BCVA), tonometry, corneal topography, AS-OCT, specular microscopy, and aberrometry. Demarcation line depth was measured centrally, 2 mm temporally, and 2 mm nasally by two independent observers using AS-OCT and was correlated with clinical parameters. RESULTS: The stromal demarcation line was visible with AS-OCT at 1 month after surgery in 28 of 29 eyes. Pairwise comparisons between the two observers of the AS-OCT measurements did not show a statistically significant difference. After an initial steepening of maximal keratometry values and a decrease in BCVA at 1 month after surgery (both with P < .012), no significant changes were found at 3, 6, and 12 months after surgery compared with before surgery. Refractive cylinder, topographic astigmatism, aberration values, endothelial cell density, and intraocular pressure remained stable during all postoperative visits. A deeper demarcation line depth was associated with a larger decrease in corneal thickness (r = -0.506; P = .012). CONCLUSIONS: AS-OCT is a useful device to detect the stromal demarcation line after corneal cross-linking. At 3 to 12 months follow-up, all clinical parameters remained stable, indicating stabilization of the keratoconic disease