Retinal Pigment Epithelium In Patients Research Articles

Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1.

PurposeRetinal and choroidal abnormalities in neurofibromatosis type 1 (NF1) remain poorly studied. It has been reported, however, that the function of the retinal pigment epithelium (RPE) in NF1 was abnormal, with a supra-normal Arden ratio of the electro-oculogram (EOG). This study aims to evaluate the function of the RPE, using EOG, first in patients with NF1 compared to controls and second in patients with NF1 with choroidal abnormalities compared to patients with NF1 without choroidal abnormalities.MethodsThis prospective case-control study included 20 patients with NF1 (10 patients with choroidal abnormalities and 10 patients without) and 10 healthy patients, matched for age. A complete ophthalmologic assessment with multimodal imaging, an EOG, and a full-field electroretinogram were performed for each included patient. The main outcome measured was the EOG light peak (LP)/dark trough (DT) ratio.ResultsThe LP/DT ratio was 3.02 ± 0.52 in patients with NF1 and 2.63 ± 0.31 in controls (P = 0.02). DT values were significantly lower in patients with NF1 than in controls (240 vs. 325 µV, P = 0.02), while light peak values were not significantly different (P = 0.26). No difference was found for peak latencies. No significant correlation between the surface and number of choroidal abnormalities and EOG parameters was demonstrated.ConclusionsThis study confirms the dysfunction of the RPE in patients with NF1, involving a lower DT and a corresponding higher LP/DT ratio. We hypothesize that this pattern may be due to a dysregulation of the melanocytogenesis, inducing a disruption in Ca2+ ion flux and an abnormal polarization of the RPE.

The Impact of Glycemic Control on Retinal Photoreceptor Layers and Retinal Pigment Epithelium in Patients With Type 2 Diabetes Without Diabetic Retinopathy: A Follow-Up Study.

AimsTo establish the sequential changes by glycemic control in the mean thickness, volume and reflectance of the macular photoreceptor layers (MPRLs) and retinal pigment epithelium in patients with type 2 diabetes without diabetic retinopathy.MethodsThirty-one poorly controlled (HbA1c > 8.0%) patients with type 2 diabetes without diabetic retinopathy undergoing glycemic control and 39 control subjects with normal HbA1c levels (< 5.9%) underwent periodical full medical, neurological and ophthalmological examinations over 2 years. Glycemic variability was evaluated by standard deviation and coefficient of variation of monthly measured HbA1c levels and casual plasma glucose. 3D swept source-optical coherence tomography (OCT) and OCT-Explorer-generated enface thickness, volume and reflectance images for 9 subfields defined by Early Treatment Diabetic Retinopathy Study of 4 MPRLs {outer nuclear layer, ellipsoid zone, photoreceptor outer segment (PROS) and interdigitation zone} and retinal pigment epithelium were acquired every 3 months.ResultsGlycemic control sequentially restored the thickness and volume at 6, 4 and 5 subfields of outer nuclear layer, ellipsoid zone and PROS, respectively. The thickness and volume of outer nuclear layer were restored related to the decrease in HbA1c and casual plasma glucose levels, but not related to glycemic variability and neurological tests. The reflectance of MPRLs and retinal pigment epithelium in patients was marginally weaker than controls, and further decreased at 6 or 15 months during glycemic control. The reduction at 6 months coincided with high HbA1c levels.ConclusionGlycemic control sequentially restored the some MPRL thickness, especially of outer nuclear layer. In contrast, high glucose during glycemic control decreased reflectance and may lead to the development of diabetic retinopathy induced by glycemic control. The repeated OCT examinations can clarify the benefit and hazard of glycemic control to the diabetic retinopathy.

Evaluation of retinal pigment epithelium changes in serous pigment epithelial detachment in age-related macular degeneration

The purpose of this study was to quantitatively evaluate retinal pigment epithelium (RPE) changes in serous pigment epithelial detachment (PED) among patients with age-related macular degeneration by means of prototype multi-contrast optical coherence tomography (OCT), which is capable of simultaneous collection of OCT angiography, polarization-sensitive OCT, and standard OCT images. We evaluated 26 eyes of 21 patients with serous PED. RPE-melanin OCT images were calculated from the multi-contrast OCT dataset and compared with near-infrared autofluorescence images. An active RPE lesion was defined as an area of thickened RPE-melanin (≥ 70 μm; RPE70) on RPE-melanin OCT. Each PED area was divided into peak and slope regions. RPE70 area ratios were compared with the maximum PED height, PED area, PED volume, and slope area ratio (area of slope region/area of whole PED). RPE-melanin OCT images were consistent with near-infrared autofluorescence images. The RPE70 area ratio in the slope region was significantly negatively correlated with the slope area ratio. Development of active RPE lesions in the slope region was correlated with the PED configuration. Multi-contrast OCT is useful for objective evaluation of changes in the RPE in patients with age-related macular degeneration.

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression.

SummaryRecent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

A Review of Macular Atrophy of the Retinal Pigment Epithelium in Patients with Neovascular Age-Related Macular Degeneration: What is the Link? Part II.

IntroductionTo explore the potential link between macular atrophy (MA) of the retinal pigment epithelium (RPE) in patients with neovascular age-related macular degeneration (nAMD) and anti-vascular endothelial growth factor (anti-VEGF) treatment.MethodsThrough a balanced overview of the field from a largely clinical perspective, we looked at available evidence on the topic of MA correlation with anti-VEGF therapy and examined possible risk factors for MA development in the context of nAMD treatment with anti-VEGF.ResultsLinks have been reported to connect both MA incidence and progression to treatment frequency and to the anti-VEGF drug type.ConclusionsAll reports agree on the fact that de novo development of MA in anti-VEGF-treated eyes is frequent and multifactorial. Research data shows an expansion of atrophy during anti-VEGF treatment. There are mixed conclusions about the correlation of MA incidence or progression with treatment-related risk factors. It mostly appears that there is no straightforward link. More clinical research is still needed to further understand this association.

Macular Atrophy of the Retinal Pigment Epithelium in Patients with Neovascular Age-Related Macular Degeneration: What is the Link? Part I: A Review of Disease Characterization and Morphological Associations.

IntroductionThe purpose of this review was to explore the potential link between macular atrophy (MA) of the retinal pigment epithelium in patients with neovascular age-related macular degeneration (nAMD) with the disease characteristics and morphological features.MethodsTo this end, we performed a search of peer-reviewed articles published on the PubMed database and included all relevant papers. We then examined these papers for possible risk factors for MA development in the context of nAMD treated with anti-vascular endothelial growth factor drugs, as well as possible protective factors.ResultsOur review of the relevant publications revealed that areas of MA can be directly visualized through multiple imaging modalities. Associations have been identified between MA of the retinal pigment epithelium and choroidal neovascular membrane characteristics, intra- and subretinal fluid, pigment epithelial detachment, choroidal thickness, subretinal hyperreflective material, outer retinal tubulations, hemorrhage, subretinal drusenoid deposits, refractile drusen, hyperreflective foci, retinal angiomatous proliferation, polypoidal choroidal vasculopathy, geographic atrophy in the fellow eye, genetic factors, and age.ConclusionThe findings of this review indicate that a multimodal approach is recommended for the assessment of MA. The conclusions drawn to date on the correlation between MA development or progression of MA and specific risk factors and possible protective factors are mixed. More clinical research is needed to reach a better understanding of this association.

Возможности ОКТ-ангиографии в режиме En Face в визуализации морфологических изменений ретинального пигментного эпителия у пациентов с острой центральной серозной хориоретинопатией

Возможности ОКТ-ангиографии в режиме En Face в визуализации морфологических изменений ретинального пигментного эпителия у пациентов с острой центральной серозной хориоретинопатией

Towards Treatment of Stargardt Disease: Workshop Organized and Sponsored by the Foundation Fighting Blindness.

Accumulation of fluorescent metabolic byproducts of the visual (retinoid) cycle is associated with photoreceptor and retinal pigment epithelial cell death in both Stargardt disease and atrophic (nonneovascular) age-related macular degeneration (AMD). As a consequence of this observation, small molecular inhibitors of enzymes in the visual cycle were recently tested in clinical trials as a strategy to protect the retina and retinal pigment epithelium in patients with atrophic AMD.To address the clinical translational needs for therapies aimed at both diseases, a workshop organized by the Foundation Fighting Blindness was hosted by the Department of Pharmacology at Case Western Reserve University on February 17, 2017, at the Tinkham Veale University Center, Cleveland, OH, USA. Invited speakers highlighted recent advances in the understanding of the pathophysiology of Stargardt disease, in terms of its clinical characterization and the development of endpoints for clinical trials, and discussed the comparability of therapeutic strategies between atrophic age-related macular degeneration (AMD) and Stargardt disease. Investigators speculated that reducing the concentrations of visual cycle precursor substances and/or their byproducts may provide valid therapeutic options for the treatment of Stargardt disease. Here we review the workshop's presentations in the context of published literature to help shape the aims of ongoing research endeavors and aid the development of therapies for Stargardt disease.

Lipofuscin-associated photo-oxidative stress during fundus autofluorescence imaging

PurposeCurrent standards and guidelines aimed at preventing retinal phototoxicity during intentional exposures do not specifically evaluate the contribution of endogenous photosensitizers. However, certain retinal diseases are characterized by abnormal accumulations of potential photosensitizers such as lipofuscin bisretinoids in the retinal pigment epithelium (RPE). We sought to determine these contributions by a numerical assessment of in-vivo photo-oxidative stress during irradiation of RPE lipofuscin.MethodsBased on the literature, we calculated the retinal exposure levels, optical filtering of incident radiation by the ocular lens, media, photoreceptors, and RPE melanin, light absorption by lipofuscin, and photochemical effects in the RPE in two situations: exposure to short-wavelength (λ = 488 nm) fundus autofluorescence (SW-AF) excitation light and exposure to indirect (diffuse) sunlight.ResultsIn healthy persons at age 20, 40, and 60, respectively, the rate of oxygen photoconsumption by lipofuscin increases by 1.3, 1.7, and 2.4 fold during SW-AF-imaging as compared to diffuse sunlight. In patients with STGD1 below the age of 30, this rate was 3.3-fold higher compared to age-matched controls during either sunlight or SW-AF imaging.ConclusionsOur results suggest that the RPE of patients with STGD1 is generally at increased risk of photo-oxidative stress, while exposure during SW-AF-imaging amplifies this risk. These theoretical results have not yet been verified with in-vivo data due to a lack of sufficiently sensitive in-vivo measurement techniques.

Frequency, Phenotypic Characteristics and Progression of Atrophy Associated With a Diseased Bruch's Membrane in Pseudoxanthoma Elasticum.

To characterize atrophy of the outer retina and the retinal pigment epithelium in patients with pseudoxanthoma elasticum (PXE). In this retrospective cross-sectional study, the frequency and phenotypic characteristics of manifest atrophy were investigated in 276 eyes of 139 patients using color fundus photography, fundus autofluorescence (AF) imaging, and spectral domain optical coherence tomography. Progression rates of atrophy were quantified in eyes with longitudinal AF recordings. Atrophy was present in 90 eyes (32%; mean age, 60; range, 32-88 years). In 19 eyes (7%; mean age, 56; range, 37-77 years) atrophy occurred without any signs for an active or fibrotic choroidal neovascularization (CNV). The frequency of both, atrophy and CNV, increased with age. In those > 60 years of age, atrophy and/or CNV were almost universally present but varied considerably in severity. Eyes with emerging pure atrophy (n = 13, no signs of CNV) showed pattern dystrophy-like changes (100%), reticular pseudodrusen (82%), and reduced choroidal thickness. Advanced atrophy was multifocal, reached beyond the arcades, and was present nasal to the optic disc. The average expansion rate of atrophy was 3.3 ± 1.3 and 1.6 ± 1.1 mm2/year (mean ± SD), in those without or with signs for CNV, respectively. Atrophy of the outer retina and the retinal pigment epithelium is a common finding in PXE patients characterized by early onset and fast progression with subsequent visual loss independent from CNV. This suggests that atrophy is the natural endpoint of Bruch's membrane disease. Phenotypic similarities with multifactorial geographic atrophy in age-related macular degeneration suggest common pathogenic pathways at the level of Bruch's membrane.

Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model.

SummaryHuman embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells could replace lost tissue in geographic atrophy (GA) but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model.

Induced to cure: Engineering iPS cell derived RPE scaffolds to treat degenerative eye diseases

SummaryThe recent success with embryonic stem (ES) cell derived retinal pigment epithelium (RPE) has provided hope for a cure for degenerative eye diseases. Induced pluripotent stem (iPS) cells are an autologous source of stem cells potentially with fewer immune‐challenges as compared to ES cells. Using a developmentally guided differentiation protocol we have developed fully polarized RPE tissue from iPS cells. The RPE monolayer along with its secreted ECM and a degradable scaffold form a tissue that mimics the native tissue in structural and functional properties. This RPE tissue performs several key RPE functions like phagocytosis of photoreceptor outer segments, ability to transport water from apical to basal side, and the ability to secrete cytokines in a polarized fashion. Currently, we are testing the safety and the efficacy of this tissue in animal models. We have begun Phase I Investigational New Drug (IND) enabling studies with the goal to transplant autologous iPS cell derived RPE in patients in advanced Geographic Atrophy stage of age‐related macular degeneration (AMD), one of the leading blinding diseases in the US. Our work will provide a potential personalized cell therapy for AMD patients.

Gene therapy to treat inherited and complex retinal degenerative diseases

Gene therapy to treat inherited and complex retinal degenerative diseases

Retinal pigment epithelium findings in patients with albinism using wide-field polarization-sensitive optical coherence tomography.

To investigate pigmentation characteristics of the retinal pigment epithelium (RPE) in patients with albinism using wide-field polarization-sensitive optical coherence tomography compared with intensity-based spectral domain optical coherence tomography and fundus autofluorescence imaging. Five patients (10 eyes) with previously genetically diagnosed albinism and 5 healthy control subjects (10 eyes) were imaged by a wide-field polarization-sensitive optical coherence tomography system (scan angle: 40 × 40° on the retina), sensitive to melanin contained in the RPE, based on the polarization state of backscattered light. Conventional intensity-based spectral domain optical coherence tomography and fundus autofluorescence examinations were performed. Retinal pigment epithelium-pigmentation was analyzed qualitatively and quantitatively based on depolarization assessed by polarization-sensitive optical coherence tomography. This study revealed strong evidence of polarization-sensitive optical coherence tomography to specifically image melanin in the RPE. Depolarization of light backscattered by the RPE in patients with albinism was reduced compared with normal subjects. Heterogeneous RPE-specific depolarization characteristics were observed in patients with albinism. Reduction of depolarization observed in the light backscattered by the RPE in patients with albinism corresponds to expected decrease of RPE pigmentation. The degree of depigmentation of the RPE is possibly associated with visual acuity. Findings suggest that different albinism genotypes result in heterogeneous levels of RPE pigmentation. Polarization-sensitive optical coherence tomography showed a heterogeneous appearance of RPE pigmentation in patients with albinism depending on different genotypes.

Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients. In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt's macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years). Three dose cohorts (50,000, 100,000, and 150,000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations. The studies are registered with ClinicalTrials.gov, numbers NCT01345006 (Stargardt's macular dystrophy) and NCT01344993 (age-related macular degeneration). There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16-25 points 3-12 months after transplantation in patients with atrophic age-related macular degeneration and 8-20 points in patients with Stargardt's macular dystrophy. The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement. Advanced Cell Technology.

Clinical analysis of 13 patients with primary intraocular lymphoma

Objective To observe the clinical features of primary intraocular lymphoma (PIOL).Methods The clinical data of 13 patients (24 eyes) of PIOL were retrospectively analyzed.In addition to routine ophthalmic examination,auxiliary examination including fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were carried out in patients without opacity of refractive media.All the patients were underwent diagnostic vitreous surgery. Eleven patients were confirmed by cellular pathology analysis,one patient was confirmed by retinal biopsy,and one patient was confirmed by neurology biopsy.The clinical features of these patients were observed.Results There were 16 eyes of nine patients (66.7％) with primary central nervous system lymphoma and PIOL,and eight eyes of four patients (33.3％) with PIOL only.The patients included five males and eight females,with a mean age of (55.7±12.6) years.Two patients were affected unilaterally and 11 patients affected bilaterally.Their visual acuity ranged from light perception to 1.0. Fourteen eyes (58.3％) were classified as isolated vitreous inflammation type and 10 eyes (41.7％) were classified as vitreous retinal type.FFA results showed that there was no abnormalities in PIOL patients of isolated vitreous inflammation type,but there were extensive lesions of retinal pigment epithelium (RPE) observed in PIOL patients of the vitreous retinal type.OCT results showed that there were no abnormalities in PIOL of patients of isolated vitreous inflammation type,but hyperreflexia between RPE and Bruch's membrane was observed in PIOL patients of vitreous retinal type.Conclusion The clinical manifestation of PIOL are diversified,mostly in bilaterally affected cases.There are extensive lesions of RPE in patients of vitreous retinal type. Key words: Lymphoma, non-hodgkin/diagnosis; Central nervous system neoplasms/complications; Eye manifestations

An eye for discovery

Vision research has often led to significant advances in our understanding of biology. There has also been particular success in translating basic research in the eye into breakthrough clinical therapies that mark important milestones for ophthalmology and also for medical research. Anti-VEGF therapy for age-related macular degeneration was named as one of the top ten science advancements of the year 2006. Only two years later, successful transfer of the RPE65 gene into retinal pigment epithelium of patients with Leber congenital amaurosis was noted as one of the most important clinical applications of gene therapy. The articles in this Review series outline current developments in vision research and highlight its continued importance in ophthalmology and medicine.

Human Retinal Pigment Epithelium Cell Changes and Expression of αB-Crystallin

To examine changes in the retinal pigment epithelium (RPE) in eyes with age-related macular degeneration (AMD) and specifically to characterize alphaB-crystallin expression in RPE cells as a biomarker in this disease. Maculae from human patients diagnosed as having AMD or from age-matched control eyes were isolated, cryosectioned, and analyzed immunohistochemically for alphaB-crystallin and for cell type-specific markers. In eyes with dry and wet AMD, alphaB-crystallin was heterogeneously expressed by a subpopulation of RPE cells in the macular region (frequently in cells adjacent to drusen) and in areas of RPE hypertrophy associated with wet AMD. In contrast, alphaB-crystallin was not detected at significant levels in control RPE. Accompanying the formation of drusen in early-stage and late-stage AMD, RPE cells undergo change to express alphaB-crystallin. The detection of alphaB-crystallin in the RPE of patients with early and advanced AMD implicates this as an AMD biomarker. Sporadic expression of alphaB-crystallin by RPE cells localized adjacent to drusen in early AMD indicates that changes in the gene expression of RPE cells accompany early stages of the disease and introduces novel potential targets for AMD therapy.

Autologous Translocation of the Choroid and Retinal Pigment Epithelium in Patients with Geographic Atrophy

To evaluate the functional and anatomical outcomes of autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in patients with geographic atrophy. Prospective nonrandomized study. Twelve consecutive patients with geographic atrophy secondary to age-related macular degeneration presenting with recent loss of reading vision. An autologous peripheral full-thickness graft of RPE, Bruch's membrane, and choroid was positioned under the macula in patients with geographic atrophy. Functional tests included Early Treatment Diabetic Retinopathy Study distant vision, reading (Radner Test, measured as logarithm of the reading acuity determination [logRAD]), threshold static perimetry, and determination of the point of fixation. Fluorescein and indocyanine green angiography, autofluorescence, and optical coherence tomography served to evaluate the anatomical outcome in a 6-month follow-up (12 months in 7 patients). Preoperative visual acuity (VA) ranged from 20/800 to 20/40 (mean, 0.6+/-0.4 logarithm of the minimum angle of resolution), and reading vision from 1.1 to 0.5 logRAD (mean, 0.8+/-0.2). Three patients were unable to read. Six months after surgery, VA ranged from hand movements to 20/32, with an increase of > or =5 letters in 2 eyes. Two patients without reading ability preoperatively were able to read after surgery. Reading was possible in a total of 8 patients after 6 months (1.3-0.4 logRAD). In 7 patients who were observed for 1 year, VA remained stable (+/-1 line) in 5 eyes and decreased in 2 eyes between 6 months' and 1 year's follow-up. In all eyes but 2, revascularization was visible on indocyanine green angiography as early as 3 weeks after surgery. Autofluorescence of the RPE was independent of revascularization of the graft and persisted throughout follow-up. Four eyes had unstable fixation and/or extrafoveal fixation before surgery. Two of these eyes stabilized during follow-up. Areas overlying atrophic areas demonstrated low threshold sensitivities that persisted after translocation of a free graft with only limited recovery. Revisional surgery due to proliferative vitreoretinopathy was required in 5 eyes. The translocation of a full-thickness graft usually results in a vascularized and functioning graft in patients with geographic atrophy, although is associated with a high risk of complications and visual loss. Longer follow-up is necessary to learn about the long-term survival and functionality of the graft.

Macular Degeneration in a Patient with Aceruloplasminemia, a Disease Associated with Retinal Iron Overload

To provide the first ophthalmic case report of a Caucasian patient with the rare autosomal recessive disease aceruloplasminemia, which results in iron overload in the retina, brain, and pancreas. Single observational case report. Perls' staining of a conjunctival biopsy was used to detect elevated iron levels in the conjunctival epithelium. Fundus photography, fluorescein angiography, and electroretinography were used to document retinal appearance and function. Unlike a report of a Japanese patient with aceruloplasminemia, who had midperipheral retinal pigment epithelium (RPE) cell atrophy and yellowish discoloration of the fundus, our Caucasian patient had a maculopathy. Beginning at age 47, he had development and progression of multiple subretinal yellowish-white lesions and RPE cell atrophy. To confirm tissue iron overload in our patient, we took the novel approach of a conjunctival biopsy, which showed Perls' Prussian blue-positive epithelial cells. Given our recent finding of elevated iron levels in the RPE of patients with age-related macular degeneration (AMD), it is interesting that retinal iron overload in aceruloplasminemia is associated with a maculopathy that clinically resembles AMD. This finding supports the hypothesis that retinal iron homeostasis is essential for normal retinal function. Disruption of iron homeostasis could contribute to the pathogenesis of AMD.