Retinal Pigment Epithelial Hyperplasia Research Articles

Multimodal imaging features in chorioretinitis sclopetaria

AbstractPurpose: To describe the multimodal imaging findings in a case of chorioretinitis sclopetaria (CS).Methods: Single case report.Results: A 26‐year‐old male reported a history of ocular injury to the right eye (OD) in childhood caused by a palm tree branch after which he underwent cataract surgery. On examination, his best‐corrected visual acuity was light perception in OD. Anterior segment examination revealed the presence of an anterior chamber intraocular lens. Intraocular pressure was within the normal range. Dilated funduscopy showed an area of bare sclera in the inferonasal quadrant adjacent to a white fibroglial proliferation that extended to the nasal and temporal periphery consistent with CS. A large area of chorioretinal atrophy involving the macular region with a nasal demarcation line and scattered hyperpigmented patches was also noted. The left eye examination was unremarkable. Fundus autofluorescence showed hypoautofluorescence of the scar tissue and in the posterior pole. Swept‐source optical coherence tomography scans confirmed the rupture of the choroid underneath a full‐thickness hyperreflectivity in the inferonasal quadrant and revealed disruptions in the macular RPE and outer retinal layers.Conclusions: CS is caused by a shock wave from a high‐velocity projectile resulting in the tearing of the choroid, retinal pigment epithelium (RPE), and neurosensory retina which later induces fibrous scarring, RPE hyperplasia, and photoreceptor loss. Multimodal imaging findings of CS are consistent with these features.

Choroideremia Gene Therapy.

Choroideremia Gene Therapy.

Structure of the Retinal Margin and Presumed Mechanism of Retinal Detachment in Choroidal Coloboma

To describe the vitreoretinal structure at the margin of the choroidal coloboma in infants and older patients using swept-source (SS) OCT. Retrospective case series. Nineteen eyes of 16 patients with choroidal coloboma (7 males, 9 females; average age, 12.3 ± 7.1 years). The patients were classified into 2 groups: infants 1 year of age or younger (3 eyes) and older patients (16 eyes). Each finding on SS OCT was documented according to previously defined histopathologic findings. Description of the SS OCT features of choroidal colobomas. Swept-source OCT showed that the extracolobomatous retina centrally traversed the margin to continue as the marginal intercalary membrane (MICM), whereas the outer layers of the MICM were reversed at the point (point of reversal [POR]). The expected duplication was seen in all infant eyes, but in none of the older eyes whose outer layers of the MICM were ambiguous. However, at the boundary between the layered MICM and monolayered central intercalary membrane (CICM), the POR was detectable in all patients. Further SS OCT analysis showed that the MICM schisis and CICM schisis occurred simultaneously with vitreous traction. Retinal detachments (RDs) seen in 4 eyes were connected to the only MICM schisis, and a MICM break was identified in 1 eye. Swept-source OCT showed that retinal pigment epithelial hyperplasia adhered tightly to the retina and that the glial triangle was adhered tightly to the sclera, indicating barriers to the development of RD after MICM schisis. Swept-source OCT first visualized the POR in infant eyes and showed that the POR was identifiable despite the atrophic changes in the outer layer of the MICM in the older eyes. Based on the POR location, we confirmed that the intercalary membranes reported in previous OCT studies were clearly differentiated between the MICM and CICM. We also showed that the presence of MICM and CICM schisis resulted from vitreous traction at the coloboma margin and that MICM breaks induced RD only if the barrier that prevented the development of RD was broken.

Retinal pigment epithelium hyperplasia overlying pigment epithelial detachment in age-related macular degeneration can masquerade as neovascularization on optical coherence tomography angiography

PurposeTo report the image artifacts due to retinal pigment epithelium (RPE) hyperplasia overlying retinal pigment epithelial detachment (PED) in age-related macular degeneration (AMD), which can masquerade as neovascularization on optical coherence tomography angiography (OCTA).MethodsA hospital-based, retrospective, and cross-sectional study. Twenty-two eyes from 16 patients with non-vascularized PED related to AMD were included in this study. All patients were examined by OCTA, spectral-domain optical coherence tomography, fluorescence angiography, and indocyanine green angiography. Vascular flow signals (VFS) on both the outer retinal slab of en face OCTA and cross-sectional OCTA and their correspondence with RPE hyperplasia were evaluated.ResultsFifteen eyes (68.2%) showed VFS on both the outer retina slab of en face OCTA and cross-sectional OCTA, all corresponding to the RPE hyperplasia overlying PED. Among them, 12 eyes with lump RPE hyperplasia outside foveal avascular zone (FAZ) all showed obvious VFS on the outer retina slab of OCTA, and 3 eyes with scattered RPE hyperplasia outside FAZ showed VFS fragments. Of note, 4 eyes had accompanied RPE hyperplasia inside FAZ, and 7 eyes without RPE hyperplasia overlying PED showed no corresponding VFS on the outer retina slab of OCTA. Additionally, a round-like dark band at the edge of PED was observed in the outer retina slab on en face OCTA in 17 eyes (77.3%).ConclusionsRPE hyperplasia overlying PED in AMD can masquerade as neovascularization on OCTA. To avoid misdiagnosis and unnecessary treatment, this RPE hyperplasia-related image artifact should be considered when interpreting OCTA images.

Genetic variant of Stickler's syndrome

Abstract Cases reports Three myopic components of a same family came for study because presented severely degraded vitreous, equatorial membranes, retinal pigment epithelium hyperplasia, vascular sheathed and sclerosis of peripheral predominance. A genetic study confirmed the diagnosis of Stickler's syndrome with a variant in the mutation of the COL2A1 gene. Discussion Stickler's syndrome should be suspected in families with a characteristic phenotype with vitreous syneresis and alterations in the retina, but there may be genetic variants that do not express the classic phenotype.

Variante genética del síndrome de Stickler

Cases reportsThree myopic components of a same family came for study because presented severely degraded vitreous, equatorial membranes, retinal pigment epithelium hyperplasia, vascular sheathed and sclerosis of peripheral predominance. A genetic study confirmed the diagnosis of Stickler syndrome with a variant in the mutation of the COL2A1 gene. DiscussionStickler's syndrome should be suspected in families with a characteristic phenotype with vitreous syneresis and alterations in the retina, but there may be genetic variants that do not express the classic phenotype.

Juxtapapillary tumors and pseudo‐tumors of the retinal pigmented epithelium

SummaryThe most conspicuous retinal pigment epithelium (RPE)‐associated lesion, most of which typically occur in the peripapillary region, is known as the combined hamartoma of the retina and the RPE although not all of them extend to the level of the RPE. This congenital lesion, which also has a vascular and an epiretinal component, often will slowly evolve during observation, not infrequently leading to reduced vision from distortion of the macula. It appears as a greyish‐brown, slightly elevated fundus lesion. It may be associated with neurofibromatosis type 2, although most seem to be isolated. None of the other RPE lesions occurs predominantly in the peripapillary region, although congenital hypertrophy of the RPE, simple hamartoma of the RPE, adenomas and adenocarcinomas of the RPE, and acquired reactive proliferations leading to RPE hyperplasia can do so. Except for the first one, these are slightly to moderately elevated lesions. Finally, rare congenital pigmentary changes such as pigmented optic disk, thought to be of RPE origin, can sometimes be observed.

SOLITARY CIRCUMSCRIBED "PEARL WHITE" RETINAL MASS (SO-CALLED RETINAL ASTROCYTIC PROLIFERATION) RESIDES IN DEEP RETINA OR BENEATH RETINA: FINDINGS ON MULTIMODAL IMAGING IN 4 CASES.

To report novel observations of previously described solitary circumscribed retinal astrocytic proliferation using spectral domain optical coherence tomography that suggests this tumor does not arise in the nerve fiber layer as initially believed, but arises within deep retinal or retinal pigment epithelial structures. Retrospective review of four cases. Patient age ranged from 46 to 75 years. The tumor was pearl white or yellow-white (n = 4, 100%), located in the macula (n = 1, 25%) or macula to equator (n = 3, 75%) regions, and with mean tumor base of 1.2 mm and thickness of 0.8 mm. There were no feeding vessels, intrinsic vessels, subretinal fluid, or vitreoretinal traction. Mild surrounding retinal pigment epithelial hyperplasia and atrophy rimmed each tumor (n = 4, 100%). Fluorescein angiography depicted the mass with early hypofluorescence (n = 3/3, 100%) and late hypofluorescence (n = 2/3, 67%). Spectral domain optical coherence tomography demonstrated the mass with an abruptly elevated "snowball" configuration (n = 4, 100%), with smooth or slightly irregular surface (n = 4, 100%), and originating from deep retina or retinal pigment epithelial (n = 4, 100%), with overlying compression and draping of retinal tissue (n = 4, 100%). This previously described small yellow-white retinal tumor appears to arise in the outer retinal layers and not from the inner retinal layers as formerly believed. This tumor may not be astrocytic as initially believed since it arises deep within the retina, but it could represent a deep glial or pigment epithelial fibrous mass. The pathogenesis and pathology of this rare lesion remain unknown.

Macular OCT features in eyes with VKH disease

PurposeTo describe choroidal and retinal patterns evaluated with SD‐OCT in patients with Vogt‐Koyanagi‐Harada (VKH) disease.MethodsWe included all patients with VKH disease according to the international workshop on VKH and referred to Pitie‐Salpetriere Hospital between December 2014 and June 2015, for whom SD‐OCT was performed. Data collection consists of assessing the best corrected visual acuity (BCVA), the dosages of corticosteroids and immunosuppressors as well as the description of retinal and choroidal thickness and architecture.ResultsThirty eyes of 15 patients, 12 females and 3 males, with an average age of 44.5 years were included. The main uveitis follow‐up was 7.1 years. Two thirds of uveitis cases were chronic. The mean VA was 0.42 logMar. OCT features were macular edema (16.7%), external limiting membrane disruption (36.7%), atrophy of nuclear layers (13.3%), ellipsoid line disruption (36.7%), retinal pigment epithelial hyperplasia and atrophy (26.7% and 16.7%), serous retinal detachment (16.7%), choroidal folds (13.7%), Sattler's and Haller's layers disorganisation (60% and 43%). Retinal and choroidal thicknesses were 259.3 μ and 325.1 μ respectively. The proportion of eyes with ellipsoid disruption, pigment epithelium atrophy and alterations of choroidal layers was more important in the group of eyes with VA superior or equal to 0.4 logMar. Uveitis duration in the first group was superior compared to the second group (5.2 vs. 11.2 years). The degree of inflammation, based on laser flare meter values, was similar.ConclusionsSevere retinal damages seem not to be so common and are frequently associated with poor visual acuity. Haller and Sattler layers alteration are common in acute and chronic cases of VKH disease. Starting rapidly corticosteroid treatment or/and immunosupressors is necessary to avoid these irreversible damages.

Phenotype of maculopathy in primary hyperoxaluria type 1

PurposeTo describe the structural and functional characteristics of oxalate retinopathy, an entity described in only 40 cases until now.MethodsFive patients with molecularly confirmed primary hyperoxaluria type 1 were subjected to multimodal retinal imaging (spectral‐domain optical coherence tomography, white light, and HRA multispectral imaging) and functional testing, including color vision testing, Goldmann perimetry, and ISCEV standard electrophysiological testing.ResultsOne patient with a c.[33dupC]; c.[731T > C] mutation showed bilateral perifoveal retinal pigment epithelium hyperplasia. The fundus in the four other patients, all of whom share an identical homozygous c.[33dupC] mutation, ranged from normal to bilateral widespread distribution of retinal crystals and confluent macular retinal pigment epithelium hyperplasia with subfoveal fibrosis. All patients who had developed end‐stage renal disease showed some sign of retinopathy, more severe with earlier onset.ConclusionsRetinopathy in primary hyperoxaluria type 1 shows considerable interindividual variation. No correlation between genotype and retinal phenotype was detected. A proposed clinical grading system of oxalate maculopathy derived from a literature review may help clinicians in estimating not only current visual function but also prognosis in this patient population that largely consists of preverbal infants.

Annular Lesions and Catenary Forms in Chronic Central Serous Chorioretinopathy

To describe a series of patients exhibiting annular retinal pigment epithelial (RPE) lesions in the context of chronic central serous chorioretinopathy. Retrospective comparative case series. Consecutive patients with chronic central serous chorioretinopathy were identified from the clinical practices of 3 retina specialists. A subset of patients exhibiting annular RPE lesions on fundus autofluorescence was included for chart review and examination of multimodal imaging (study group). Patients with alternative etiologies for neurosensory detachment or pigment epitheliopathy were excluded. A second consecutive cohort of patients, with acute central serous chorioretinopathy, was also examined for the presence of annular lesions (comparative group). Sixty-seven patients with chronic central serous chorioretinopathy were identified. Fourteen eyes of 12 patients exhibited annular lesions (study eyes). Mean visual acuity of study eyes was 20/27 (logMAR 0.13, SD 0.11). Annular lesions were composed of hyperautofluorescent stellate lesions arranged in an open or closed ring with intervening foci of punctate hypoautofluorescence. Optical coherence tomography showed RPE hyperplasia at the perimeters of annular lesions with loss of ellipsoid reflectivity and preserved RPE at the lesion center. Annular lesions were confined to the posterior poles and appeared to have developed at the margins of chronic neurosensory detachment. Forty-three eyes of 30 patients with acute central serous chorioretinopathy comprised the comparative group and none of these eyes exhibited annular lesions. Annular lesions occur in up to a fifth of patients with chronic central serous chorioretinopathy but carry a relatively good visual prognosis. Curvilinear RPE figures and demarcation lines are seen in various retinal conditions but the characteristics of annular lesions described here suggest that they are specific to chronic central serous chorioretinopathy.

Choroidal melanoma

To review the current features and classification of choroidal melanoma, and to identify the lesions that clinically simulate choroidal melanoma (pseudomelanoma). Uveal melanoma is a serious life-threatening intraocular malignancy, most often found in Caucasians (98%) and primarily involving the choroid (90%), ciliary body (7%), or iris (2%). This review will concentrate on choroidal melanoma. At diagnosis, choroidal melanoma usually appears as a pigmented (85%) tumor underlying the retina with a median basal dimension of 11 mm and a mean thickness of 4.5 mm. The American Joint Committee on Cancer classification allows for categorization and staging of melanoma. Following ocular therapy, adjuvant systemic therapy is provided for patients with high-risk melanoma who demonstrate alterations in chromosomes 3, 6, and 8 or those with class 2 on gene-expression profiling, detected by needle biopsy or solid tumor biopsy. The prognosis of choroidal melanoma depends most importantly on the genetic alterations and tumor size. Every millimeter increase in thickness leads to a 5% increased risk for metastasis. The leading conditions that simulate choroidal melanoma include choroidal nevus, peripheral exudative hemorrhagic chorioretinopathy, congenital hypertrophy of the retinal pigment epithelium (RPE), hemorrhagic RPE detachment, choroidal hemangioma, age-related macular degeneration, RPE hyperplasia, and others. These pseudomelanomas can be differentiated from choroidal melanoma by their unique clinical features. Choroidal melanoma is a serious malignancy with characteristic features. Early detection and therapy is important. Pseudomelanomas can lead to diagnostic confusion; however, clinical features aid in differentiation.

An interesting case of "bear track dystrophy"

Bear track dystrophy, is a rare condition, which forms part of the disorder known as the grouped congenital hypertrophy of the retinal pigment epithelium (CHRPE), a peculiar congenital anomaly of the retinal pigment epithelium diagnosed by its characteristic ophthalmoscopic appearance. This disorder is usually without any functional consequence with patients typically having a normal vision, color vision, normal visual fields, dark adaptation, electroretinography, and electrooculography findings. The main differential diagnosis of CHRPE includes choroidal naevus, choroidal melanoma, chorioretinal scar, subretinal hematoma, pigmented epiretinal membrane, and reactive retinal pigment epithelial hyperplasia. Since CHRPE, in itself is a totally benign condition with no associated ocular or systemic complications, it becomes that much more important to distinguish it from the more serious vision/life-threatening conditions like choroidal melanoma as well as from the other pigmented ocular fundus lesions associated with familial cancer syndromes like familial adenomatous polyposis.

Congenital and other pigmented fundus lesions

AbstractPurpose: To describe congenital and pigmented fundus tumors except nevi and melanomas. Methods: We analyse diagnostic approaches of thess tumors, their characteristics, the differential diagnosis and the follow up. Results: The main tumors include congenital tumors such as congenital hypertrophy of the retinal pigment epithelium (RPE), hamartoma of the RPE, combined hamartoma of the RPE and sensory retina. The other pigmented tumors are melanocytoma, adenoma or adenocarcinoma of RPE and pigmented choroidal metastasis. The differential diagnosis must be made from RPE hyperplasia, peripheral exsudative haemorrhagic chorioretinopathy and pseudo tumoral age related macular degeneration. Conclusions: These tumors must be known to be differenciated from melanomas and choroidal nevi. Moreover, although these lesions are mainly benign in their clinical behavior, some cases can have ocular complications, slow growth or malignant transformations.

Different treatment modalities for choroidal neovascularization in two eyes of one patient with bilateral type 2A parafoveal telangiectasia

A 60-year-old diabetic man presented with a history of decrease in vision in both eyes since 2 weeks. At presentation, best corrected visual acuity (BCVA) in the right eye (RE) was 20/30 and that in the left eye (LE) was 20/80. The right fundus revealed a grayish reflex, yellowish crystalline deposits and retinal pigment epithelial hyperplasia at the macula. The left fundus showed subretinal fluid and temporal subretinal hemorrhage near a grayish reflex at the macula. A diagnosis in both eyes of idiopathic macular telangiectasia (IMT) type 2A with RE stage 4 and LE stage 5, choroidal neovascularization (CNVM) was made. The patient was treated with photodynamic therapy (PDT) in LE. The visual acuity improved to 20/40 over the next 6 months. At a 4-year follow-up, he developed decreased vision in RE diagnosed as IMT with CNV and was treated with intravitreal ranibizumab. At 6-month follow-up post injection, the vision was 20/40p.

Ocular Abnormalities and Systemic Disease in Down Syndrome

Introduction: Ocular problems as refractive errors, strabismus, accommodation, and cataract are well known in children with Down syndrome (DS). However, there is little information on the possible correlation of eye problems with systemic diseases such as heart defect (with or without surgery), hypotony, hypothyroidism, hearing loss, and others.Methods: Ophthalmic problems versus certain systemic diseases were studied in 65 children with DS, aged 2 months to 13 years, referred to the University Eye Hospital Ljubljana, Slovenia from 2008 to 2010. Standard ophthalmic examination methods were used, and physical data were taken from pediatric records.Results: Ocular findings included nystagmus (29.2%), esotropia (26.1%), epiphora (21.5%), Brushfield spots (16.9%), lens opacities (12.3%), abnormalities of the retinal vessels, foveal hypoplasia, or retinal pigment epithelium hyperplasia (32.2%), and optic disc pallor (7.6%). Hyperopia (36.9%) was the most frequent refractive error in the group, followed by astigmatism (29.2%) and myopia (24.6%). No diagnosed systemic abnormalities were found in 18.3% of the children, while 30.7% had congenital heart defect. Hypothyroidism, hypotony, hearing loss, gastrointestinal tract malformations, and leukemia were less common. Nystagmus was related to myopia and esotropia, and to heart disease and heart operations.Conclusions: Comorbidities are common in DS and complicate diagnosis, development, and therapy.

Retinal Pigment Epithelial Trough: a Sign of Chronicity of Choroidal Nevi

To describe the clinical features and natural course of choroidal nevi with retinal pigment epithelial (RPE) trough. Retrospective observational case series. Of the 90 patients (91 choroidal nevi), 88 (98%) were Caucasian and 59 (66%) were women, with a mean age of 56 years (range 18-79 years) at presentation. The mean largest nevus basal diameter was 7 mm (range 3-12 mm) and the mean thickness was 2.2 mm (range 0.8-3.4 mm). Orange pigment and subretinal fluid were associated with 9 (10%) and 16 (18%) of the nevi, respectively. Overlying RPE alterations included RPE atrophy (93%), RPE hyperplasia (74%), drusen (54%), and RPE fibrous metaplasia (36%). Retinal pigment epithelial trough was present at initial evaluation in 88 eyes and developed during follow-up from a long-standing pocket of shallow subretinal fluid in 3 other eyes. The mean largest dimension of the RPE trough was 4 mm (range 1-16 mm) and most (76%) were located at the inferior margin of the nevus. Of 91 nevi, 82 had subsequent follow-up with a mean follow-up duration of 79 months (range 3-464 mo). Of these, 19 (23%) showed slight growth and only 3 (4%) had presumed transformation into melanoma. None of the patients showed evidence of distant metastasis. Retinal pigment epithelial trough results from resorption of long-standing serous subretinal fluid and should therefore be considered a sign of chronicity of choroidal nevi. Choroidal nevi associated with RPE trough, despite their greater thickness and larger size, are relatively stable with minimal risk of progression into melanoma.

Transient subretinal hemorrhage after photodynamic therapy of subfoveal choroidal osteoma.

To report a case of choroidal osteoma that developed subretinal hemorrhage after photodynamic therapy (PDT). Interventional case report. An 8-year-old boy was brought to our attention because of mild visual loss in his left eye. The visual acuity was 20/25. A subfoveal yellow-orange-colored lesion, measuring 5.0 mm × 4.5 mm in base diameter was detected in the left eye. B-mode ultrasonography showed an acoustically solid 2.0-mm-thick mass with orbital shadowing. Orbital computed tomography confirmed the presence of calcium, and choroidal osteoma was diagnosed. As there was a decrease in the best-corrected visual acuity (20/30) and the lesion showed growth (6.0 mm × 6.0 mm), PDT was performed at 6 months follow-up. The day after PDT, the visual acuity was counting fingers at 1 m and a subretinal hemorrhage over the lesion was detected. Two weeks after PDT, subfoveal hemorrhage dissappeared with some retinal pigment epithelial hyperplasia and visual acuity increased back to 20/30. Although PDT can induce decalcification in choroidal osteomas, it should not be performed in subfoveal osteomas unless there is evidence to treat the lesion such as the presence of choroidal neovascularization.

Iron-mediated retinal degeneration in haemojuvelin-knockout mice

Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins HFE (human leucocyte antigen-like protein involved in iron homoeostasis), transferrin receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Recent studies have established the expression of all of the five genes in the retina, indicating their importance in retinal iron homoeostasis. Previously, we demonstrated that HJV is expressed in RPE (retinal pigment epithelium), the outer and inner nuclear layers and the ganglion cell layer. In the present paper, we report on the consequences of Hjv deletion on the retina in mice. Hjv-/- mice at ≥18 months of age had increased iron accumulation in the retina with marked morphological damage compared with age-matched controls; these changes were not found in younger mice. The retinal phenotype in Hjv-/- mice included hyperplasia of RPE. We isolated RPE cells from wild-type and Hjv-/- mice and examined their growth patterns. Hjv-/- RPE cells were less senescent and exhibited a hyperproliferative phenotype. Hjv-/- RPE cells also showed up-regulation of Slc7a11 (solute carrier family 7 member 11 gene), which encodes the 'transporter proper' subunit xCT in the heterodimeric amino acid transporter xCT/4F2hc (cystine/glutamate exchanger). BMP6 (bone morphogenetic protein 6) could not induce hepcidin expression in Hjv-/- RPE cells, confirming that retinal cells require HJV for induction of hepcidin via BMP6 signalling. HJV is a glycosylphosphatidylinositol-anchored protein, and the membrane-associated HJV is necessary for BMP6-mediated activation of hepcidin promoter in RPE cells. Taken together, these results confirm the biological importance of HJV in the regulation of iron homoeostasis in the retina and in RPE.

Subretinal fibrosis in stargardt's disease: case report

The authors describe the clinical characteristics of a 14-year-old female patient with ophthalmoscopic and angiographic aspects of Stargardt's disease in both eyes who developed subretinal fibrosis and localized retinal pigment epithelial hyperplasia in the posterior pole of the right eye 6 months after a mild blunt trauma to the right globe. The left fundus remains with the typical presentation of Stargardt's disease. Our findings support the theory that ocular trauma occurring in patients with Stargardt's disease can precipitate a sequence of events leading to the development of subretinal fibrosis and significant visual loss.