Pigment Epithelium Alterations Research Articles

Retinocytoma Associated with Calcified Vitreous Deposits

To report a case of bilateral retinocytoma associated with calcified vitreous deposits. Case report. On routine examination, a 35-year-old asymptomatic father of a child with bilateral retinoblastoma presented bilateral retinocytoma associated with vitreous calcifications, in the vicinity of the retinocytoma in his left eye. Fundus photographic documentation and fluorescein angiography were performed. The patient has been followed up for 10 years. The lesions in both eyes have remained stable without signs of growth or malignant transformation. Calcified vitreous deposits are a recently described feature of retinocytoma in addition to the three classic features: translucent retinal mass, retinal pigment epithelial alteration, and calcification.

Factors Predictive of Tumor Growth, Tumor Decalcification, Choroidal Neovascularization, and Visual Outcome in 74 Eyes With Choroidal Osteoma

To evaluate choroidal osteoma for tumor growth, tumor decalcification, related choroidal neovascularization, visual acuity loss, and poor visual acuity. Retrospective nonrandomized single-center case series. Ocular Oncology Service at Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pa. There were 74 eyes of 61 patients with choroidal osteoma evaluated between January 1, 1977, and January 1, 2003. The 5 outcome measures included tumor growth, tumor decalcification, related choroidal neovascularization, visual acuity loss of 3 or more Snellen lines, and poor visual acuity of 20/200 or worse. At 5 and 10 years, Kaplan-Meier analysis revealed tumor growth in 22% and 51% of eyes, tumor decalcification in 28% and 46% of eyes, choroidal neovascularization in 31% and 31% of eyes, visual acuity loss in 26% and 45% of eyes, and poor visual acuity in 45% and 56% of eyes, respectively. The clinical factor predictive of tumor growth was absent overlying retinal pigment epithelial alterations. The factor predictive of decalcification was irregular tumor surface. Of the 15 tumors that showed partial decalcification at the first visit, there was no further tumor growth in any case. Of the remaining 12 tumors that later developed decalcification, tumor growth, if it occurred, was along the margin opposite the decalcification. No tumor showed growth in the region of decalcification. Factors predictive of choroidal neovascularization included irregular tumor surface and subretinal hemorrhage. In 6 eyes that had both choroidal neovascularization and tumor decalcification, the neovascularization was detected prior to or at the same time as the decalcification. The factor predictive of visual acuity loss was presence of subretinal fluid whereas the factors predictive of poor visual acuity included symptoms and tumor decalcification. A comparison of eyes with subfoveal vs extrafoveal choroidal osteoma showed poor visual acuity in 15 (34%) of 44 eyes and 3 (10%) of 30 eyes, respectively. Eyes with decalcified choroidal osteomas manifested poor visual acuity in 13 (48%) of 27 eyes whereas those with nondecalcified tumors showed poor visual acuity in 5 (11%) of 47 eyes. Choroidal osteoma showed evidence of growth in 51% of eyes and decalcification in nearly 50% of eyes by 10 years. Tumors with any degree of decalcification at the initial visit showed no further growth. Overall, poor visual acuity of 20/200 or worse was found in 56% of eyes by 10 years, and decalcified subfoveal choroidal osteomas displayed a particularly poor visual prognosis.

Severe pigment epithelial alterations in the treatment area following photodynamic therapy for classic choroidal neovascularization in young females

Although photodynamic therapy (PDT) is an established treatment for choroidal neovascularization (CNV), the mechanisms are still not completely elucidated. Damage to the retinal pigment epithelium (RPE) was observed following uncomplicated PDT in young patients. Observational case series. Four female patients between the age of 26 and 39 years presented with visual loss because of classic CNV. In two 39 years old females the CNV originated secondary to a small chorioretinal scar, in a 26 and a 36-year-old woman the CNV was of idiopathic cause. All patients received standard PDT according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study protocol. One to three months after an uncomplicated PDT with verteporfin, severe pigment epithelial alterations in the treatment area were observed. The neovascular membranes responded favorably to the treatment and demonstrated fibrosis and resolution of leakage. Ophthalmoscopically and angiographically, atrophy of the retinal pigment epithelium was seen precisely delineating the size of the treatment spot used. Vision declined in two patients from 0.3 to 0.1 and 0.15 to 0.1. The two other patients demonstrated an increase of visual acuity from 0.7 to 0.9 and from 0.4 to 0.9. The retinal pigment epithelium alterations did not resolve during follow-up, but remained unchanged in area and intensity. Characteristic retinal pigment epithelium alterations were observed in young female patients with small classic CNV following PDT. Unusual retinal pigment epithelium damage in young female patients without any associated disease might be related to a possible inherent defect in the RPE or to the hormonal status of this specific patient population.

Fundus features of a case of neurocutaneous melanosis

A 5-year-old girl with giant cutaneous congenital melanocytic nevi was examined because of right esotropia. She had multiple uveal coloboma-like lesions of various sizes and irregular areas of retinal pigment epithelial alterations in the right fundus. Magnetic resonance imaging studies demonstrated right-sided ventriculomegaly, right intraventricular presumed dysplastic neuroectodermal tumor, and right-sided cortical migration anomaly. The clearly lateralized ocular, cutaneous, and central nervous system findings in this patient may point towards a probable common underlying pathogenetic mechanism involving the neural crest cells at the center stage. These findings also help to strengthen the view that neurocutaneous melanosis may represent a rare form of phakomatosis.

Assessment of mutations in the best macular dystrophy ( VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull’s-eye maculopathy

Purpose To study the presence of Best macular dystrophy ( VMD2) gene mutations in patients diagnosed with maculopathies other than classic Best disease and to describe the clinical characteristics of these subjects. Design Case-comparison study of phenotype-genotype correlations. Methods Patients with either age-related maculopathy (ARM; n = 259) or maculopathies other than classic Best disease (n = 28) were screened for mutations in the Best gene ( VMD2; OMIM 153700). These cases were compared with ethnically similar subjects in the same age range without maculopathy (n = 196). All patients underwent a complete dilated ocular examination, and all affected individuals underwent fundus photography. Phenotype-genotype comparisons were made. Main outcome measures Presence of mutations in the Best gene ( VMD2; OMIM 153700) and the clinical phenotype. Results Three of 259 patients (1%) with ARM and 2 of 28 patients (7%) with other maculopathies including 1 of 3 patients with adult-onset foveomacular vitelliform dystrophy and 1 of 5 patients with a bull’s eye maculopathy, but none of the controls, were found to possess amino acid-changing variants in the VMD2 gene. These included a man with confluent drusen and retinal pigment epithelial detachments (variant in exon 6; T216I), a man with geographic atrophy and numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations resembling bull’s-eye maculopathy (variant in exon 4; E119Q), and a woman diagnosed with adult-onset foveomacular vitelliform dystrophy (variant in exon 4; A146K). Conclusions Novel mutations in the VMD2 gene were found in patients diagnosed with maculopathies other than classic Best disease. Some cases diagnosed as adult-onset vitelliform foveomacular dystrophy may represent a variant of Best disease with delayed onset. The VMD2 gene does not play a major role in the development of ARM.

Observations on 17 patients with retinocytoma.

To study the clinical features and natural history of 17 patients with retinocytoma. A retrospective case series. Tertiary referral center. Data on 17 patients with retinocytoma were reviewed for clinical features. The natural history of retinocytoma and its risk for malignant transformation were also evaluated. Among 920 consecutive patients who had retinoblastoma, retinocytoma, or both, we identified 24 tumors in 17 patients (1.8%) with clinical features compatible with retinocytoma. The median age at diagnosis was 15 years (range, 4-45 years). Of the 24 tumors, the retinocytoma was bilateral in 3 cases (13%) and the family history of retinoblastoma was positive in 3 cases (13%). Seventeen (71%) of the tumors were extramacular in location, and 7 (29%) were located in the macular area. Ophthalmoscopic features characteristic of retinocytoma included the presence of a translucent retinal mass in 21 (88%), calcification in 15 (63%), and retinal pigment epithelial alteration in 13 (54%) of the 24 tumors. A combination of all 3 features was observed in 8 (33%) of the 24 tumors. In 13 (54%) of the tumors, a zone of chorioretinal atrophy could be observed. In 1 patient, subtle tumor regression was documented photographically. Only 1 retinocytoma (4%) underwent malignant transformation into retinoblastoma. At the last follow-up visit, none of the patients had developed a pineoblastoma or another second malignant neoplasm. Retinocytoma is a rare benign retinal tumor that has characteristic clinical features. The areas of chorioretinal atrophy were suggestive of tumor regression. In our series, the risk for malignant transformation of retinocytoma into retinoblastoma was 4%; therefore, patients with a presumed diagnosis of retinocytoma should be closely observed.

Case-control study of the risk factors for age related macular degeneration

AIMA case-control study was initiated to determine the risk factors for the development of age related macular degeneration (AMD).METHODSStudy participants, who were all white, aged 50–85 years, and were recruited...

Retinal Pigment Epitheliopathy after Macular Hole Surgery

Full-thickness idiopathic macular holes were previously considered untreatable, but surgical intervention has been proposed to collapse the hole and improve vision. This study evaluates the fluorescein angiographic changes that occur after macular hole surgery. Sixteen patients with stage III idiopathic macular holes underwent pars plana vitrectomy, removal of the posterior hyaloid, peeling of fine epiretinal sheets along the edges of the holes, and fluid-gas exchange. Preoperative fluorescein angiograms were performed, and best-corrected preoperative visual acuity was 20/200 or less in all eyes. Postoperatively, the macular hole disappeared in 12 eyes (75%). In all 12 eyes, retinal pigment epithelial swelling was present, with a unique fluorescein angiographic appearance. This pattern slowly resolved over months, with gradual visual improvement but residual retinal pigment epithelial mottling. Systemic and periocular steroids had no significant impact on the process. The combination of prolonged intraocular gas contact and light exposure exceeding threshold for an already compromised macula appears to be responsible for this pigmentary pattern. Depending on the severity of the pigment epithelial alteration, this unique pattern may portend a guarded visual prognosis in affected patients undergoing successful macular hole repair.

Müller cell changes precede vascularization of the pigment epithelium in the dystrophic rat retina

In the Royal College of Surgeons rat with inherited retinal dystrophy, photoreceptor cell degeneration is accompanied by retinal pigment epithelial (RPE) cell alterations and Müller cell changes such as increased expression of glial fibrillary acidic protein (GFAP). Vascular changes such as vascularization of the RPE, vascular proliferation, and formation of vitreoretinal membranes (VRMs) are observed later. To study the relationship of Müller cell changes to the vascular alterations in the dystrophic retina, we used immunoperoxidase techniques and antibodies against GFAP and vimentin. Our study showed that during photoreceptor degeneration, Müller cells expressed small amounts of GFAP. As degeneration progressed, GFAP expression increased and morphological alterations occurred in Müller cells. Müller cell apical processes extended and proliferated in the subretinal space and contacted the apical surface of duplicated RPE cells. Later, GFAP reactive fibers surrounded retinal vessels apposed to the RPE. As the vessels became enmeshed within the RPE, the GFAP-positive perivascular processes disappeared. Eventually, the RPE-associated vessels became displaced into the inner retina where VRMs were sometimes observed. Immunoblots showed increased GFAP in dystrophic as compared with control retinas. Studies of vimentin distribution in the dystrophic retina showed results similar to the GFAP study. Moreover, the vimentin study suggested increased number of Müller cell processes in the dystrophic as compared with control retinas. The close temporal and anatomical relationships among Müller cell, RPE, and vascular changes in the dystrophic rat suggest a role for Müller cells in retinal neovascularization and proliferative retinopathy.

Hereditäre Drusen der Bruchschen Membran

The left eye of a 71-year-old patient who had suffered from choroiditis guttata was removed immediately after death by enucleation. Histopathological studies revealed numerous nodular (hard) drusen, a wide variety of senile alterations of the pigment epithelium and Bruch's membrane, and the presence of multiple corpora arenacea in the subarachnoid space of the optic nerve. A new hypothesis concerning the development of hereditary drusen is advanced, postulating a disturbance of the lysosomal enzyme/inhibitor balance.

Neoplastic Angioendotheliomatosis: A Variant of Malignant Lymphoma Immunohistochemical and Ultrastructural Observations of Three Cases

Neoplastic angioendotheliomatosis (NAE) is a rare, fatal disease characterized by widespread intravascular proliferations of malignant cells of putative endothelial origin. Clinically, dermatologic and bizarre neurological manifestations predominate, but review of the reported cases of NAE reveals ophthalmic involvement to be frequent. To our knowledge, no reports of NAE have appeared in the ophthalmic literature. We describe three cases of NAE with the ocular manifestations of visual loss, cells in the vitreous, retinal artery occlusion, retinal vascular and pigment epithelial alterations, nystagmus, and cortical blindness. Autopsies (including eyes and central nervous system) revealed pancorporal involvement by intravascular anaplastic cells in each patient. In two patients massive extravascular involvement was also present. The tumor cells lacked ultrastructural features of endothelial cells and failed to stain for factor-VIII-related antigen. Common leukocyte antigen, a maker for hematopoietic cells, particularly lymphocytes, was detected on tumor cells in all cases, indicating that NAE is probably an extranodal lymphoma. The dramatic response of the central nervous system lesions to radiotherapy in one case supports this contention. It is suggested that this disorder be treated as a malignant lymphoma.

Unilateral Purtscher's Retinopathy

Four patients with unilateral Purtscher's retinopathy are described. Fluorescein angiography demonstrated impaired arteriolar flow, capillary non-perfusion, venous staining, retinal edema, and optic disc edema. Resolution exceeded three months with variable degrees of permanent visual loss, optic atrophy, and pigment epithelial alteration. The pathogenesis of Purtscher's retinopathy is unknown. Arterial embolization, possibly air from the lungs, seems to be the most plausible explanation.

Dominant Slowly Progressive Macular Dystrophy

Twenty-three members of one white family were studied for a new form of dominant slowly progressive macular dystrophy in which visual acuity remained good until the seventh decade. Ten patients had positive signs of this entity. Eight patients had possible early forms. Five had no signs. Several patients had visual acuity fluctuations, documented by their ophthalmologists who saw associated pigment epithelial alterations in some cases. Obvious macular changes included perifoveal pigment epithelial atrophy, posterior pole flecks, and fundus lesions resembling an atrophic form of senile macular degeneration. We suggest a possible hereditary predisposition to senile macular degeneration in our patients.

Late Macular Complications of Choroidal Ruptures

Late complications of ocular contusion have been widely studied. Attention is fre­ quently directed to the anterior segment, to late onset glaucoma and its relation to angle recession. Posteriorly, late onset of retinal detachment is well recognized. Recently de­ layed damage to the macula related to ad­ jacent choroidal ruptures causing late visual symptoms has been recognized by Gass' and Fuller and Gitter. Choroidal rupture is a common complica­ tion of contusion injuries of the eye. Such rents in the choroid (and in Bruch's mem­ brane) usually occur temporal to the disk in a concentric fashion and are often associ­ ated with intrachoroidal, subretinal, and intraretinal hemorrhage. The usual course of such injuries is one of gradual clearing of localized hemorrhage and retinal or choroidal edema with formation of a gliotic scar and pigment epithelial alterations in the area of the choroid tear. If the macula has not been directly involved, good visual acuity is to be expected. Usually the area remains essentially unchanged. Gass and others,' however, have observed hemorrhagic detachment of the pigment epi­ thelium as a late complication of choroidal rupture. Fuller and Gitter described a case in which subretinal neovascularization and serous detachment of the macula occurred six months after choroidal rupture. Patients with choroidal rupture should be followed with the potential complication in mind. Fluorescein angiography is useful in detecting and observing the changes in the choroidal rupture. Our report concerns three additional cases