Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg Health Study.

BACKGROUND: The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort. METHODS: We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD). RESULTS: Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 µm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD. CONCLUSIONS: In this study, the prevalence of AMD increased dramatically with age; however, although AMD is usually thought to occur after age 50, signs of early AMD were found in 3.8% of individuals in the youngest age group (younger than 45 years). This population-based sample is the first to provide substantial epidemiologic data from a large German cohort, including data on macular degeneration in younger age groups and incidence data after recall.

Distribution of intraocular pressure and its association with ocular features and cardiovascular risk factors: the Gutenberg Health Study.

PURPOSE: To describe the distribution of intraocular pressure (IOP) and its association with ocular features and cardiovascular risk factors in an adult European cohort. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: This analysis was based on a Gutenberg Health Study (GHS) cohort that included 4335 eligible enrollees from among 5000 subjects who participated in the survey from 2007 through 2008. The age range was 35 to 74 years at enrollment. METHODS: Participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination including slit-lamp biomicroscopy, noncontact tonometry, fundus photography, central corneal thickness measurement, and visual field testing; and a thorough general examination focused on cardiovascular parameters, psychological evaluation, and laboratory tests, including genetic analysis. MAIN OUTCOME MEASURES: Mean and reference interval of IOP stratified by age, gender, and eye. RESULTS: Mean ± standard deviation (SD) IOP was 14.0 ± 2.6 mmHg in both eyes, 13.9 ± 2.7 mmHg in right eyes, and 14.0 ± 2.7 mmHg in left eyes. Mean ± SD IOP in men (n = 2216) and in women (n = 2119) was 14.1 ± 2.7 mmHg and 13.9 ± 2.5 mmHg with an intersex difference (P = 0.009). Positive univariate associations with higher IOP were detected for brown iris color, central corneal thickness, hypertension, diabetes, smoking, obesity, dyslipidemia, body mass index, weight, hip size (women only), waist circumference, and waist-to-hip ratio. Multivariate testing revealed male gender, central corneal thickness, brown iris color, hypertension, smoking, and waist-to-hip ratio to be correlated with higher IOP. In women, age correlated negatively with IOP in the multivariate analysis. CONCLUSIONS: Intraocular pressure distribution in this cohort yielded a lower mean IOP than in similar white study populations. Increasing age in women correlated with lower IOP. Association analyses with several systemic characteristics revealed that cardiovascular risk factors correlated with higher IOP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

SPARC is expressed in scars of the Tenon's capsule and mediates scarring properties of human Tenon's fibroblasts in vitro.

PURPOSE: To investigate the expression of the matricellular protein SPARC (secreted acidic cysteine-rich glycoprotein) in scarred human Tenon's capsule and in cultured human Tenon's fibroblasts (HTF), and to analyze the influence of SPARC on cell proliferation and collagen matrix contraction in vitro. METHODS: Human Tenon's capsule scars obtained from surgical revisions after filtration surgery were analyzed for SPARC expression by immunohistochemistry. In cultured HTF cells, SPARC expression was assessed by northern and western blot analyses after incubation with transforming growth factor (TGF)-ß1 and TGF-ß2. Cell proliferation was determined by bromodeoxyuridine (BrdU)-labeling and HTF cells-mediated collagen matrix contraction by morphometric measurements of three-dimensional collagen lattices after treatment with SPARC and/or TGF-ß1. RESULTS: In scarred human Tenon's capsule specimens, an increased expression of SPARC was mainly localized to the extracellular matrix and to blood vessel walls as compared to healthy control Tenon's capsule. In cultured HTF cells, treatment with TGF-ß1 more than TGF-ß2 induced the expression of SPARC both on the mRNA and protein level. Incubation of HTF cells with SPARC resulted in an increase in collagen matrix contraction and cell proliferation. Moreover, a combined incubation of SPARC and TGF-ß1 stimulated HTF cell proliferation significantly over the levels that were observed after single treatment. CONCLUSIONS: Our data provide evidence that SPARC contributes to excessive wound healing and scar formation in human Tenon's capsules after filtration surgery and may thus represent a novel target for anti-fibrotic strategies.

Impact of the line of sight on toric phakic intraocular lenses for hyperopia.

We present a hyperopic patient with a decentered line of sight in whom the residual refractive error after toric phakic intraocular lens (TP IOL) implantation was improved by displacement and individualized treatment. A 35-year-old woman presented with asthenopic complaints 2 months after bilateral TP IOL implantation and IOL rotation 4 weeks later. Examination revealed the line of sight to be nasally and inferiorly decentered in relation to the center of the pupil. A more nasal reenclavation of the TP IOL decreased the coma, and the uncorrected visual acuity was 20/20. We conclude that line of sight should be measured before TP IOL implantation, especially in hyperopic eyes.

Histopathologic findings in early encapsulated blebs of young patients treated with the ahmed glaucoma valve.

OBJECTIVE/AIM: Uncontrolled glaucoma presents a challenge for the ophthalmic surgeon especially in children and juvenile patients. For many patients who have undergone failed surgical procedures before, episcleral implants remain the last choice. Encapsulated blebs forming over antiglaucoma devices present a complication leading to malfunctioning or even failure with reincrease in intraocular pressure. We report our histopathologic findings of such blebs developing around the Ahmed glaucoma valve (AGV) after a short time period in young patients. MATERIALS AND METHODS: Nine young patients (2 to 17 y of age) with otherwise uncontrollable glaucoma were treated with AGV (models FP-7 and FP-8, silicone base plate) by 1 surgeon (H.T.). Four eyes needed surgical revision 2 to 6 months after initial implantation owing to encapsulated bleb development over the valve with total loss of function. The dense capsule around the device was surgically removed and investigated macroscopically, microscopically, and ultrastructurally. RESULTS: The cystic wall of these encapsulated blebs had an overall thickness of 1.5 to 2 mm. Macroscopically, the tissue was split into 2 layers. Histopathologically, the smooth inner surface (facing the base plate of the AGV) consisted of compressed collagen fibers with signs of elastoid degeneration and with formation of a pseudoendothelium toward the base plate. There was a pronounced transformation of fibroblasts into myofibroblasts in this inner layer. The outer area was highly vascularized. In these vessels electron microscopy revealed thrombosis. Inflammatory responses were nearly absent in all areas of the excised material. Intraocular pressure could be controlled by removal of the encapsulated blebs in all 4 cases. CONCLUSIONS: Encapsulation of the AGV is an early complication in young patients, leading to inhibition of fluid exchange and failure of the procedure. The valve mechanism is blocked by contracted scar tissue, but the device itself is not affected by the encapsulation. Surgical excision of the capsule immediately leads to an aqueous flow and drop of intraocular pressure.

Comparative effects of TGF-beta 1 and TGF-beta 2 on extracellular matrix production, proliferation, migration, and collagen contraction of human Tenon's capsule fibroblasts in pseudoexfoliation and primary open-angle glaucoma.

PURPOSE: To comparatively investigate the effects of TGF-beta(1) and TGF-beta(2) on extracellular matrix production, proliferation, migration, and collagen contraction of cultured human Tenon's capsule fibroblasts derived from patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma, primary open-angle glaucoma (POAG), and cataract. METHODS: Tenon's capsule fibroblasts obtained from four groups of patients were cultured and stimulated with different concentrations (0.1-10 ng ml(-1)) of TGF-beta(1) or TGF-beta(2) for up to 14 days. Cell proliferation was determined with the WST-1 colorimetric assay, cell migration by using the Transwell assay system, and collagen contraction by computerised analysis of three-dimensional collagen lattices and immunohistochemistry for alpha-smooth muscle actin expression. Expression and synthesis of extracellular matrix components (fibronectin, collagen types I and III) was assessed by enzyme-linked immunosorbent assays, by real-time RT-PCR, and by transmission electron microscopy. RESULTS: Both TGF-beta(1) and TGF-beta(2) in pathophysiological concentrations of 0.1-5 ng ml(-1) stimulated cell proliferation, migration, collagen contraction, alpha-smooth muscle actin expression as well as mRNA expression and secretion of fibronectin, collagen type I, and collagen type III by Tenon's fibroblasts derived from all groups of patients. TGF-beta stimulation occurred in a concentration-dependent manner with different peak activities associated with different fibroblast functions. There was some variability among the different groups of patients with an increased response of cells derived from PEX and POAG patients as compared to cataract patients. Although no statistically significant differences were found between both TGF-beta isoforms, TGF-beta(1) had a more pronounced stimulatory effect on expression and synthesis of extracellular matrix components including the production of elastic microfibrils, particularly in cells derived from patients with PEX syndrome/glaucoma. CONCLUSIONS: These findings suggest a significant contribution of TGF-beta(1) in addition to TGF-beta(2) to the conjunctival scarring process following glaucoma filtration surgery. Due to its pronounced fibrogenic potential, TGF-beta(1) may become another focus for targeting drug therapy, particularly in patients with PEX glaucoma.

[Complications of a voluminous congenital ciliary body cyst]. / Komplikationen einer grossen kongenitalen Ziliarkörperzyste.

BACKGROUND: Multiple cysts of iris and ciliary body may cause many complications such as acute or chronic angle closure glaucoma. PATIENT: We present a boy with multiple congenital cysts of the iris pigment epithelium and a voluminous cyst of the unpigmented ciliary body epithelium of the right eye. This resulted in lenticular astigmatism, concomitant strabismus divergens and subsequently to anisometropia. The voluminous cyst (8 x 12 mm in diameter) was folded around the lens, reached the optic axis and resulted in displacement of the lens and contact between the iris and the corneal endothelium from 6.30 to 11. After puncture and partial resection of the cyst at the age of 8 months the boy developed a subcapsular multivesicular cataractic clouding of the temporal lens and a progredient myopia (up to - 14.0/- 2.0/0 degrees ); in contrast the left eye was hyperopic (+ 3.5/- 3.75/0 degrees ). The lens was subluxated superonasally due to congenital damage of the zonular fibres. Because development of visual acuity seemed limited by these determinants (20/200 at the right eye), cataract surgery with posterior capsulorhexis, anterior vitrectomy, and implantation of a capsular tension ring and posterior chamber intraocular lens was performed at the age of nearly five. Actually, there is an orthotropia, best corrected visual acuity in the distance of 20/32 in the right and 20/20 in the left eye; binocular vision is somewhat restricted. CONCLUSION: Usually congenital cysts are clinically not very relevant; occasionally surgical intervention is required to ensure adequate development of visual acuity.

Orbital involvement in multiple myeloma: first sign of insufficient chemotherapy.

Orbital involvement in multiple myeloma is unusual. We describe the case of a 60-year-old male who presented with left proptosis, reduced visual acuity, diplopia and progressing signs of globe indentation 2 months after chemotherapy for multiple myeloma. MRI showed a well-defined tumor filling the mediobasal part of the left orbit. Incisional biopsy and reduction of tumor mass were performed using an anterior transconjunctival orbitotomy. Histopathologic findings and further systemic examination confirmed the reactivation of the multiple myeloma. Proptosis, intraocular pressure and visual acuity improved following external beam radiation therapy of the left orbit and repeated systemic chemotherapy. Orbital involvement in multiple myeloma was the only sign of insufficient chemotherapy.

Isolated neurofibroma of the orbit with extensive myxoid changes: a clinicopathologic study including MRI and electron microscopic findings.

Isolated orbital neurofibroma (INO) without systemic neurofibromatosis is rare. Previous reports including MRI with elaboration of the ultrastructural features of the cellular and extracellular components in INO do not exist. A 44-year-old male presented with painless, slowly progressive proptosis (6 mm) and downward displacement (3 mm) of the left eye of two years duration. MRI revealed a suprabulbar mass hypointense to fat, isointense to brain on T1-weighted images with small hyperintense areas following contrast enhancement. T2-weighted images showed a predominantly hyperintense mass with a few hypointense islands. The lesion was excised using an anterior superior transseptal orbitotomy. Histopathologically, large areas of a paucicellular myxoid stroma containing mucopolysaccharides made up approximately three-quarters of the mass. Focal hypercellular areas showed marked collagen deposition. Blood vessels were distributed at the periphery of the lesion and in association with nodules of nerve sheath cells. Ultrastructurally, perineural and fibroblast-like cells were loosely arranged in a myxoid stroma. Schwann cells were embedded in a dense collagenous matrix. Variable differentiation of Schwann cells, perineural cells and fibroblast-like cells associated with a more solid (collagenous) or loose (myxoid) extracellular matrix may determine the characteristic, though not specific, MRI features in isolated neurofibromas of the orbit.

Histological examination of an eye with endogenous Aspergillus endophthalmitis treated with oral voriconazole: a case report.

PURPOSE: To report the histological findings of an eye with severe Aspergillus endophthalmitis after oral treatment with voriconazole. METHODS. Case report. RESULTS: Histopathological examination revealed no fungal elements in choroidal or retinal vessels. The hyphae were mainly restricted to the vitreal side of the preretinal inflammatory infiltrate. Since the treatment with voriconazole had not been completed at the time of enucleation, the clinical course with potential further limitation or regression of the lesion remains unsettled. CONCLUSIONS: Endogenous Aspergillus endophthalmitis is a devastating condition often associated with immunodeficiency. The pathogenesis of this entity implies the primary invasion of choroidal and retinal vessels. The lack of antifungal drugs with high blood-ocular permeability results in an extremely poor visual prognosis. Our histological examination indicates promising activity and ocular penetration of the new antifungal agent voriconazole.