Retinal Deposits Research Articles

Autoantibody profile against retinal proteins in patients with age-related macular degeneration and possible role in neovascularization (137.13)

Abstract Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the United States and in other developed countries. Recent findings indicate that circulating autoantibodies specific for retinal proteins and macular deposits, drusen, are associated with AMD pathogenesis, yet only a few antibodies have been identified in sera from patients with AMD. In order to reveal an autoantibody profile for AMD, we performed an antigen microarray with constituents of drusen and liquid chromatography and tandem mass spectrometry analysis following two-dimensional immunoblot analysis with retinal proteins using serum samples from patients with AMD and healthy controls. Sera from the AMD group contained high levels of IgG autoantibodies against numerous ocular antigens including lipoproteins and collagen when compared to the normal group. Moreover, IgGs purified from sera of AMD patients induced more tube formation on choroidal-retinal endothelial cells and increased VEGF production on monocytes compared to those of healthy donors. Our data suggest that these IgG autoantibodies may be used as biomarkers for AMD and contribute to progression of this disease.

Bietti crystalline dystrophy with bilateral macular holes.

Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. Case report and literature review. Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear.

Retinal artery occlusion and multiple retinal deposits as a consequence of therapeutic arteriovenous fistula embolization.

To describe a rare case of a patient who underwent a therapeutic arteriovenous fistula embolization and developed painful vision loss in one eye and to describe the clinical course, present sequential images, and propose an explanation. The record of one patient with subretinal deposits, including fundus photographs and fluorescein angiography, was reviewed. Fundus photographs show creamy white circumscribed subretinal deposits. Fluorescein angiography shows evidence of retinal and choroidal ischemia. This patient had anomalous anatomy with an ophthalmic artery arising from the middle meningeal artery. This allowed the embolic material to reflux into the ophthalmic circulation and deposit in the retinal and choroidal circulation, causing infarcts.

Idiopathic juxtafoveal retinal telangiectasia

Background Idiopathic juxtafoveal retinal telangiectasia (IJRT) is a rare retinal condition that can be detected even in asymptomatic patients. The most common appearance, type 2A, typically presents as juxtafoveolar telangiectasias with minimal exudation, superficial retinal crystalline deposits, and right-angle venules. Though initially asymptomatic, late complications such as foveolar atrophy and subretinal neovascularization can develop and should be recognized and treated accordingly. Case Report Two patients with IJRT are presented. The first patient, a 60-year-old Hispanic man, had asymptomatic type 2A IJRT with subretinal neovascularization diagnosed for which he underwent photodynamic therapy on 2 separate occasions. Currently, his visual acuity remains stable at 20/30 in the treated eye. The second patient, a 78-year-old man, had bilateral type 2A IJRT with decreased vision. Fluorescein angiography found no active leakage, and optical coherence tomography found significant foveal atrophy. Therefore, no treatment was advised, and the patient remains with acuities of 20/100- in the right eye and 20/80- in the left. Conclusion Initially, retinal signs can be subtle in type 2A IJRT, with no treatment being indicated. In the late stages of the disease, laser photocoagulation may be necessary to treat subretinal neovascular membranes, which can result as a complication, leading to dramatic vision loss if the fovea is affected. Careful inspection, including the use of fluorescein angiography and ocular coherence tomography, is often helpful in monitoring these patients.

Iatrogenic retinal diamond deposits: an unusual complication of using the diamond-dusted membrane scraper

Iatrogenic retinal diamond deposits: an unusual complication of using the diamond-dusted membrane scraper

In vivo observations of chlorpromazine ocular deposits in a patient on long‐term chlorpromazine therapy

Chlorpromazine is known to deposit in ocular tissues when taken at high doses for prolonged periods. Chlorpromazine therapy in a 59-year-old schizophrenic man with a cumulative dosage exceeding 2500 g resulted in multiple white deposits in both corneas especially in the endothelium. Confocal microscopy revealed significant pleomorphism and polymegethism of endothelial cells. The anterior lens capsules opacities were star-shaped and concentrated in the centre. Because of cataract and chronic angle closure glaucoma our high-myopic patient underwent surgery, and light microscopic evaluation of the obtained anterior lens capsule during cataract surgery showed golden brown cytoplasmic deposits in the central epithelial cells and capsule. The peripheral epithelial cells of the removed capsule had no deposit. There were no sign of retinal deposits in the fundoscopy, optical coherence tomography and fluorescein angiography. In this patient chlorpromazine deposited mainly in the corneal endothelium, central anterior lens capsule and epithelial cells.

A microstructural retinal analysis of membrano-proliferative glomerulonephritis type II

Membranoproliferative glomerulonephritis type II (MPGN type II)/dense deposit disease (DDD) is characterised by electron deposits within the lamina densa of the glomerular basement membrane. Systemic manifestation may include lipodystrophy and...

Evaluation of the common variants of the ABCA4 gene in families with Stargardt disease and autosomal recessive retinitis pigmentosa

Stargardt disease (STGD) is one of the most common autosomal recessive retinal dystrophies with an estimated incidence of one in 10,000. It affects the central retina (macula). Retinitis pigmentosa (RP) comprises a large and exceptionally heterogeneous group of hereditary disorders of the retina. It is caused by the loss of photoreceptors. The condition is a degenerative disorder characterized by retinal pigment deposits and has an estimated incidence of one in 4,000. Although, to date, 45 known loci have been identified, none of them independently account for a substantial portion of RP. Recently, the photoreceptor cell-specific ATP-binding cassette transporter (ABCA4) gene was found to be mutated in patients with STGD as well as autosomal recessive RP. In order to further understand the contribution of this gene to the susceptibility to STGD and RP, we analyzed three unrelated STGD families and one autosomal recessive RP family specifically for the more common variants (A1038V, G1961E, 2588G-->C, R943Q or 2828G-->A) in the ABCA4 gene. Our analyses employing standard techniques such as polymerase chain reaction, restriction fragment length polymorphism, and direct DNA sequencing of amplified products were able to identify one common variant (R943Q) in all three STGD families but not in the RP family. All three affected STGD individuals, however, were heterozygous for this variation, and this alteration did not segregate with the disease and was also present in the normal controls. Similar analysis of other common variants revealed no pathogenic mutations in the STGD and RP families. It is likely that the variant identified in this study represents a rare polymorphism (non-pathogenic). Although, at present we cannot eliminate the possibility of this gene as a candidate gene, future extensive studies on this as well as other candidate genes may uncover the susceptibility gene for these recessive forms of the disorders in these families.

Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up

Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up

Novel CYP4V2 Gene Mutation in a Mexican Patient with Bietti's Crystalline Corneoretinal Dystrophy

Purpose: To report the clinical and genetic analysis of a Mexican female patient with a sporadic Bietti's crystalline corneoretinal dystrophy. Methods: Ophthalmological examination included best-corrected visual acuity, slit lamp examination, applanation tonometry, fundus photography, fluorescein retinal angiography, Goldmann kinetic perimetry, corneal rotating Scheimpflug imaging, and anterior segment optical coherence tomography (Visante OCT). Genetic analysis included PCR amplification and direct nucleotide sequencing of the entire CYP4V2 gene in DNA from the propositus and her relatives. Results: A late-stage retinal dystrophy was established in the patient. No retinal or corneal crystalline deposits were evident during clinical evaluation. Retrospective analysis of fundus imaging disclosed the presence of retinal crystalline deposits, suggesting the diagnosis of Bietti's crystalline corneoretinal dystrophy. Molecular analysis of the CYP4V2 gene revealed the presence of a novel C to T mutation at nucleotide position 974 (exon 7), predicting a threonine to isoleucine replacement at amino acid position 325. Corneal deposits were not seen by biomicroscopy, corneal OCT, or specular microscopy but were evidenced by means of the corneal rotating Scheimpflug imaging. Conclusion: Our results expand the allelic heterogeneity of Bietti's crystalline corneoretinal dystrophy. This is the first patient of Latin-American origin in which a molecular analysis of the disease has been performed. Our results suggest that the use of corneal rotating Scheimpflug imaging can evidence corneal deposits that are not apparent by other methods.

Reversibility of Tamoxifen® Retinopathy—A Ten-Year Follow-Up

High doses of the non-steroidal oral antiestrogen tamoxifen (60 mg/m/day or more for at least 1 year) may cause decreased visual acuity due to retinal crystalline deposits and other ocular side-effects. A 56-year-old female patient suffering from pulmonary lymphangioleiomyomatosis (BML) with paraneoplastic estradiol production was presented with deterioration of visual acuity because of bilateral macular degeneration after an intake of 190–250 mg/day Tamoxpuren for five years. After discontinuing tamoxifen, ocular side-effects disappeared, perimetric and electrophysiological alterations almost normalized while visual acuity increased internal medical findings remained stable.

Retinoid requirements in the reproduction of zebrafish

This study examines whether retinoids are essential in the reproduction of zebrafish. Using RT-PCR, it was shown that the ovaries and testes express enzymes that synthesize and metabolize the hormone retinoic acid (RA) ( raldh2 and cyp26a, respectively), and RA receptors ( raraa, rarga, rxrba, rxrbb, rxrga but not rxrab). Three new isoforms of rxrba were also observed in a variety of tissues. In other experiments, zebrafish were exposed for 11 d to diethylaminobenzaldehyde (DEAB), an inhibitor of RA synthesis, or fed a retinoid deficient diet for 130 d in order to evaluate the functional requirements of retinoids in reproduction. DEAB altered cyp26a transcript numbers in the gonads, suggesting an impact on RA, and decreased the number of spawned eggs by 95%. The retinoid deficient diet decreased whole body retinoids (retinol and retinal) by 68% in females and 33% in males. Females fed the retinoid deficient diet also produced 73% fewer eggs that contained 78% less retinal than controls. Fertilization rates were not affected. These studies have shown that the RA receptors are expressed in zebrafish gonads, and RA is required for the spawning of eggs. Dietary retinoid content influences reproduction, while retinyl ester storage levels appear to be of little significance. Females were more susceptible to retinoid perturbation than males, likely due to the cost of retinal deposition in the eggs. Overall, these studies have shown retinoids play a fundamental role in the reproduction of zebrafish, and the lack of retinyl ester stores in controls that successfully spawned illustrates that we have only a limited understanding of the retinoid physiology and requirements of fish.

Enfermedad de coats recidivante diagnosticada en sujeto adulto

A male diagnosed with Coats disease at the age of 30 years, had a relapse of this condition 14 years later. His first symptom of blurred vision occurred in both episodes and similar findings of unilateral retinal exudation and lipid deposition at boundary were seen. Angiography showed the characteristic early hyperfluorescence of the telangiectasias and late leakage of dye. Coats disease is relatively uncommon and, as the degree of involvement varies from case to case, a randomized, prospective study of treatment would probably not be feasible. Despite the characteristic features of this disease, the differential diagnoses must be considered in both children and adults.

Peripheral retinal neovascularization in talc retinopathy

Background Neovascularization of the peripheral retina can be present in a number of systemic and ocular diseases. Very rarely, peripheral retinal neovascularization can also be manifested in intravenous drug abusers. In addition to ocular complications, intravenous drug abusers are at high risk for contracting various infections and the development of pulmonary and cardiovascular diseases. We present a case of a chronic heroin and cocaine abuser with bilateral peripheral retinal neovascularization, pulmonary complications, and a history of endocarditis. Case report A patient with a 20-year history of heroin and cocaine abuse initially presented for a routine eye examination. Fundus examination revealed pinpoint white deposits centered in both maculas, engorged vascular fronds with a patch of intraretinal hemorrhage in the peripheral retinal of the right eye and neovascularization of the disc as well as exudation with adjacent focal preretinal hemorrhage in the left eye. The patient underwent fluorescein angiography and was screened for diabetes, sarcoidosis, and sickle cell disease. When no systemic disease could be discovered, it was concluded that the peripheral retinal neovascularization developed as a result of vascular occlusion from heroin and cocaine abuse. Discussion It is important to investigate the cause of neovascularization in the peripheral retina. Retinal vascular emboli such as talc are common in drug abusers, but in most cases, the retinal deposits pose only a minimal threat to vision. However, this case shows that careful retinal examination is warranted in drug abusers to rule out neovascularization of the retina. Other causes of peripheral retinal neovascularization should be ruled out as well. These conditions include sickle cell retinopathy, sarcoidosis, diabetic retinopathy, blood dyscrasias, retinal vascular occlusion, Eales’ disease, and other systemic conditions, so that appropriate ocular and systemic treatment can be provided. Peripheral retinal neovascularization is best treated by pan-retinal photocoagulation.

Peripheral Retinopathy and Maculopathy in High-dose Tamoxifen Therapy

To describe the clinical, angiographic, and optical coherence tomography (OCT) features of high-dose tamoxifen retinopathy in three male patients. Observational case series. A review of history, clinical examination, and findings on fluorescein angiography (FA) and optical coherence tomography (OCT) was conducted. Three male patients receiving high-dose tamoxifen therapy sought treatment for vision loss and a crystalline maculopathy. Crystalline deposits were noted in the peripheral retina of two patients. All the patients showed macular leakage by FA, but cystoid macular edema (CME) on OCT was detected in two patients. Inner retinal hyperreflective deposits were identified by OCT in all the patients. High-dose tamoxifen therapy may result in peripheral crystalline retinopathy in addition to perifoveal opacities. Angiographic evidence of macular edema may not unanimously correlate with presence of CME on OCT in these cases.

The effects of copper and benzo[ a]pyrene on retinoids and reproduction in zebrafish

This study examines whether a link exists between toxicant exposure, retinoids and reproduction in fish. Zebrafish were fed a control diet (8.1 μg Cu/g diet, 0 μg benzo[ a]pyrene/g diet) or diets containing elevated copper (100 μg, 500 μg and 1000 μg Cu/g diet) or benzo[ a]pyrene (B[ a]P; 30 and 150 μg B[ a]P/g diet) for 260 days. Toxicant-supplemented diets did not affect growth or mortality rates. While whole body retinoid levels in control zebrafish decreased during the experiment, females exposed to Cu or B[ a]P for 200 days or more experienced additional losses of retinyl esters (45–100% depleted) and retinal (45% depleted in B[ a]P-fed fish). Despite the reduced retinoids, Cu and B[ a]P did not effect reproduction with respect to the number of eggs spawned, fertilization rates or egg retinal content (retinal was instead increased 55–65% in eggs from B[ a]P-fed fish). There were no apparent deformities observed in 36 h post fertilization embryos from any treatment. It appears that although internal retinoid stores were depleted in adults, dietary retinoids were sufficient to meet the daily requirement for retinal deposition in the eggs and retinoic acid synthesis. This study has shown that retinoid levels in female zebrafish are sensitive to Cu and B[ a]P, and are a good indicator of long-term exposure. It also brings to light the resiliency of the retinoid system in fish and the importance of the diet on the toxicological response. Specifically that dietary retinoids appear to support normal reproduction in the absence of internal retinoid stores.

Cone rod dystrophies

Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, and the visual prognosis is poor. Management aims at slowing down the degenerative process, treating the complications and helping patients to cope with the social and psychological impact of blindness.

Prevalence of Retinitis Pigmentosa in Urban and Rural Adult Chinese: The Beijing Eye Study

To determine the prevalence of retinitis pigmentosa in the elderly Chinese population. The Beijing Eye Study is a population-based, cross-sectional cohort study and included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%) with an age of 40+ years. Readable fundus photographs were available for 4027 (90.7%) subjects. Diagnostic criteria for retinitis pigmentosa were visual field defects on frequency doubling perimetry, typical ophthalmoscopic abnormalities such as retinal pigment deposits, retinal arteriole attenuation, and pigment epithelial atrophy, and no other reason for perimetric defects and fundus abnormalities. Retinitis pigmentosa was diagnosed in four subjects (all men). Its prevalence was 0.099+/-3.15% (95% CI: 0.00, 0.2). Retinitis pigmentosa with typical fundus appearance and functional loss may be present in about 1 out of 1000 elderly Chinese in Northern China. Calculated for the whole population in China, the figure would be 1.3 million patients with retinitis pigmentosa.

Retinitis pigmentosa

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis).

Ocular presentations of breast cancer

Breast cancer is the most common malignancy in women, with increasing incidence in Europe and North America. The frequency of involvement of the eye and visual pathways is reported to be as high as 30% in patients with known metastatic disease. In some cases, ophthalmic involvement can be the first sign of metastatic spread. Metastasis occurs via the haematogenous route and predominantly involves the choroid. Metastases to other ocular structures, the orbit and the visual pathways have also been described. Paraneoplastic effects are rare but significant. Different modalities are employed in the treatment of breast cancer and its metastases. These include chemotherapy and radiotherapy. The ocular adverse effects of these have been well described, but recently developed new treatment modalities, such as monoclonal antibodies, may have different side-effects. With the increasing incidence of breast cancer and the advent of new treatment strategies, the complications of the disease and the sequelae of therapy are highly relevant to both oncologists and ophthalmologists.