Ghost Vessels Research Articles

Deletion of Ocular Transforming Growth Factor β Signaling Mimics Essential Characteristics of Diabetic Retinopathy

Diabetic retinopathy, a major cause of blindness, is characterized by a distinct phenotype. The molecular causes of the phenotype are not sufficiently clear. Here, we report that deletion of transforming growth factor β signaling in the retinal microenvironment of newborn mice induces changes that largely mimic the phenotype of nonproliferative and proliferative diabetic retinopathy in humans. Lack of transforming growth factor β signaling leads to the formation of abundant microaneurysms, leaky capillaries, and retinal hemorrhages. Retinal capillaries are not covered by differentiated pericytes, but by a coat of vascular smooth muscle-like cells and a thickened basal lamina. Reactive microglia is found in close association with retinal capillaries. In older animals, loss of endothelial cells and the formation of ghost vessels are observed, findings that correlate with the induction of angiogenic molecules and the accumulation of retinal hypoxia-inducible factor 1α, indicating hypoxia. Consequently, retinal and vitreal neovascularization occurs, a scenario that leads to retinal detachment, vitreal hemorrhages, neuronal apoptosis, and impairment of sensory function. We conclude that transforming growth factor β signaling is required for the differentiation of retinal pericytes during vascular development of the retina. Lack of differentiated pericytes initiates a scenario of structural and functional changes in the retina that mimics those of diabetic retinopathy strongly indicating a common mechanism.

Mature vessel occlusion after anti-VEGF treatment in a retinal arteriovenous malformation

BackgroundTo report engorged vessel occlusion after repeated intravitreal injections of bevacizumab to treat the macular oedema in a case of arteriovenous malformation.Case presentationA 37-year-old woman presented with a sudden, painless loss of vision in her left eye. Her visual acuity was 20/200 in the left eye, and 20/20 in the right eye. Ophthalmoscopic examination revealed an abnormal tangle of vessels and enlarged draining veins. A fluorescence angiogram revealed fluorescence leakage at a turn near the fovea. Horizontally oriented optical coherence tomography revealed an increased macular thickness and an accumulation of intraretinal fluid, indicating macular oedema. After three intravitreal injections of 1.25 mg bevacizumab, her vision improved to 20/20. Ophthalmoscopic examination revealed a decreased calibre of the previously engorged draining veins and ghost vessels. Repeated horizontally oriented optical coherence tomography revealed a decreased macular thickness and the absence of an intraretinal cyst. At the 2-year follow-up visit, the vision of the patient was stable.ConclusionThis finding implies that certain middle-size vessels can become occluded during anti- vascular endothelium growth factor (anti-VEGF) therapy, which could induce fatal complications if it occurred in the heart or brain. Clinicians should be cautious of the potential thrombotic effects on systemic blood vessels when administering anti-VEGF treatment.

A case of branch retinal artery obstruction complicated after anterior ischemic optic neuropathy.

To report a case of branch retinal artery obstruction (BRAO) complicated after anterior ischemic optic neuropathy (AION). A 42 year-old woman who complained of visual disturbance was performed ophthalmological examinations such as fundus photography, fluorescent angiography (FAG) and visual field test. At first visit, disc swelling was noted and arterial circulation was intact, however, 1 week after onset, the inferior branch retinal artery began to shrink and the flame hemorrhage intensified. Sixteen months later, the optic disc evidenced an atrophic change; additionally, a ghost vessel in the inferior branch retinal artery was found. We report a case of complications of BRAO arising after AION which caused the mechanical compression on the arterial circulation.

Choriocapillaris Vascular Dropout Related to Density of Drusen in Human Eyes with Early Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a common, potentially blinding disease characterized by the presence of extracellular deposits beneath the retinal pigment epithelium (RPE). Choroidal vascular changes have also been noted in AMD. This study examined the relationship between the choroidal vasculature and extent of drusen and other sub-RPE deposits, the key pathologic landmarks of AMD. Sections of the maculas of 45 human eyes (21 early AMD and 24 age-matched control) were evaluated morphometrically. The cross-sectional area of sub-RPE deposits, vascular density, number of CD45+ leukocytes, and number of "ghost vessels" were determined in a masked fashion and evaluated by regression analysis. In addition, the extramacular vascular density either directly beneath drusen or adjacent to drusen was evaluated in a separate set of donor eyes. The vascular density of the choriocapillaris showed a trend toward decreasing in association with AMD status. By linear regression analysis, vascular density was inversely associated with sub-RPE deposit density (r(2) = 0.22, P < 0.01). The number of ghost vessels was negatively correlated with vascular density (r(2) = 0.55, P < 0.001) and positively correlated with sub-RPE deposit density (r(2) = 0.57, P < 0.001). In morphologic studies of extramacular solitary drusen, vascular density beneath drusen was found to be 45% lower than adjacent to drusen (P < 0.01). These findings support the concept that microvascular changes are related to the pathogenesis of AMD and suggest that vascular endothelial cell loss occurs in association with sub-RPE deposit formation. Whether microvascular events are a cause or consequence of drusen or other deposit formation remains to be determined.

Late Onset of Deep Corneal Vascularization: A Rare Complication of Intrastromal Corneal Ring Segments for Keratoconus

To report deep corneal vascularization noted 3 years after intrastromal corneal ringsegments (Intacs) implantation for the treatment of keratoconus. A 33-year-old male keratoconus patient intolerant to rigid gas permeable contact lens in the right eye underwent Intacs implantation. At 2 years postoperatively, slit-lamp examination of the right eye revealed superficial corneal vascularization inferotemporally, extending 1.5 mm from the limbus. At 3 years postoperatively, the slit-lamp examination of the right eye revealed deep stromal vascularization extending to and arborizing along the temporal segment. Also, superficial vascularization was noted along the nasal segment inferiorly. The Intacs segments were then explanted. On post-explantation day 10, the deep vessels regressed to ghost vessels with topica corticosteroid therapy. The authors present a rare case where deep corneal vascularization was noticed 3 years following Intacs implantation for keratoconus. All patients having superficial vascularization away from the incision site need to be followed for this rare complication.

Time Course of Angiogenesis and Lymphangiogenesis After Brief Corneal Inflammation

To study the time course of angiogenesis and lymphangiogenesis in the cornea after a short inflammatory insult. This might be helpful for the timing of corneal transplantation in high-risk eyes. The mouse model of suture-induced inflammatory corneal neovascularization was used. After placement of 3 interrupted 11-0 sutures into the corneal stroma of BALB/c mice (left in place for 14 days), corneas were excised 2, 3, 5, 7, 14, and 21 days as well as 1, 2, 3, 6, and 8 months after surgery. Hem- and lymphangiogenesis were evaluated using double immunohistochemistry of corneas with CD31/PECAM1 as panendothelial and LYVE-1 as lymphatic endothelial marker. Both blood and lymphatic vessels grew into the cornea as early as day 2 after suture placement. The outgrowth was initially parallel. Hem- and lymphangiogenesis peaked around day 14. Thereafter, both vessel types started to regress. Regression of lymphatic vessels started earlier and was more pronounced than that of blood vessels. Whereas at 6 and 8 months (partly) perfused CD31+++/LYVE-1(-) blood vessels and (nonperfused) ghost vessels could still be observed, there were no CD31+/LYVE-1+++ lymphatic vessels detectable beyond 6 months after this short inflammation. After a temporary inflammatory insult to the cornea, there is initially parallel outgrowth of both blood and lymphatic vessels. But thereafter, lymphatic vessels regress earlier than blood vessels and are completely regressed by 6 months. Earlier regression of pathologic corneal lymph versus blood vessels suggests that corneal graft survival in high-risk eyes might best be delayed for a prolonged interval following an inflammatory insult.

Neovascularization in Experimental Retinal Venous Obstruction in Rabbits

Purpose: To investigate the later pathohistological changes in experimental retinal venous obstruction in rabbits. Methods: Experimental retinal venous obstruction was produced in retinal blood vessels of rabbits by trans-adventitial dropping of thrombin. Fundus observation was performed 3 months and 1 year thereafter. Retinal histological examinations were performed by fluorescein microscopy, light microscopy, and transmission electron microscopy. Results: Vessels with a rete mirabile and arteriovenous anastomosis were observed after 3 months. On a flat gelatin-fluorescein preparation, regions with no perfusion, thought to be areas of vascular occlusion in the periphery, were observed extensively. Clear leakage of gelatin-added fluorescein was noted from vessels in the periphery, and minute neovascularization with a rete mirabile from these vessels was confirmed. Newly formed retinal vessels were also observed by transmission electron microscopy. The endothelial cells of these newly formed vessels had a large nucleus, a number of ribosomes, and thin basement membrane. Proliferative changes included glial cells that had penetrated into the basement membrane of ghost vessels. Conclusion: Our long-term observations confirmed that proliferative changes and neovascularization occurred in this model of retinal venous obstruction.

Corneal pannus resolved with silicone hydrogel contact lenses: a case series

Corneal pannus, defined as widespread superficial corneal neovascularization, appears as a collection of vessels and fibrous tissue growing just underneath the corneal epithelium. It is commonly associated with hydrogel contact lens wear.1 In a normally avascular cornea, the presence of corneal pannus with contact lens wear has been associated with hypoxic stress.2–5 This has been reported in the literature and observed clinically when hydrogel contact lenses are used on an extended wear schedule.6 However, corneal pannus has also been documented with the daily wear of hydrogel contact lenses correcting high myopia5 as well as in the inferior corneal with the use of prism ballasted toric hydrogel lenses.7 While this type of corneal neovascularization does not typically lead to vision loss, it does indicate tissue compromise. The new fragile vessels can lead to localized, secondary hemorrhage.8 If left unchecked, it can ultimately lead to corneal opacification and subsequent vision loss.9,10 It may also be of concern for patients contemplating corneal refractive surgery (PureVision Manufacturer’s Booklet, Bausch and Lomb, Rochester, NY, March 1999). Clinically, patients who have been diagnosed with significant corneal pannus are managed by reducing contact lens wearing time and even discontinuing contact lens wear. This almost always results in quieting the anterior segment inflammation and collapsing of contact lensinduced corneal neovascularization into “ghost” vessels.1 Chan and Weissman found that corneal neovascularization regressed when these patients were refit with rigid gas permeable contact lenses (oxygen permeability 50 10 11 cm ml O2/s ml mmHg). Conversely, if hydrogel contact lens wear was continued, corneal pannus remained and even progressed.5 With the introduction of silicone hydrogel contact lenses, oxygen transmissibility (Dk/t) in the ranges of 110– 175 cm ml O2/s ml mmHg is available (Manufacturer’s package inserts, CIBA Vision Duluth, GA; Bausch and Lomb Rochester, NY). Under these oxygen-rich conditions, superficial neovascularization appears to collapse into ghost vessels or even resolve completely. We report three retrospective, chart-reviewed cases where daily wear hydrogel contact lens patients with corneal pannus were refit with silicone hydrogel contact lenses. In all three cases, corneal pannus either regressed with the wearing of silicone hydrogel contact lenses or corneal pannus regressed with discontinuation of contact lens wear and remained quiet when contact lens wear was resumed using silicone hydrogel contact lenses.

Vascular Remnants in the Rabbit Vitreous Body. II. Enzyme Digestion and Immunohistochemical Studies

The purpose of this study was to evaluate the composition of ghost vessels and the newly identified intravitreal structures type 1 and 2 (IVS-1 and 2) observed in the rabbit vitreous body. Rabbit eyes (n=10, 0.5–∼36 months of age) were fixed and embedded in plastic. Post-embedding immuno transmission electron microscopy and enzyme digestion methods specifically directed at vascular extracellular matrix components (collagen IV, elastin and hyaluronan) were used in order to confirm the postulated vascular origin of IVS-1 and 2. In addition, markers of vitreous extracellular matrix components (collagen II, hyaluronan) were used. The postulated vascular nature of ghost vessels and IVS-1 was confirmed by a positive labelling with anti-collagen IV, whereas the demonstration of elastin (by anti-elastin antibodies and elastase digestion) in IVS-1 and 2 confirms their arterial origin. These vascular remnants were also labelled with a hyaluronan marker and with anti-collagen II. The presence of remnants of the hyaloid artery system throughout the vitreous matrix is in conflict with a strict spatial separation between the primary and secondary vitreous during embryonic development as proposed in the literature. It strongly supports an alternative theory which suggests an interactive remodelling of this matrix. The presence of hyaluronan in remnants of the hyaloid system is inconclusive, since hyaluronan is a component both of the adult vitreous matrix and of the vascular extracellular matrix. The presence of collagen II in vascular structures is highly interesting, since it supports another challenging theory, which suggests that lamellae develop alongside tracts formerly occupied by the larger hyaloid vessels.

Vascular Remnants in the Rabbit Vitreous Body. I. Morphological Characteristics and Relationship to Vitreous Embryonic Development

Using light and transmission electron microscopy, we observed novel structures in the rabbit vitreous body. They were found in 18 out of 27 eyes from rabbits 0.5–36 months of age. These structures are scattered throughout the entire vitreous matrix. By light and transmission electron microscopy, they appear to be made up of the same structural components. Based upon their morphological appearance, they can be subdivided into two groups which we provisionally named ‘intravitreal structure type 1 and 2’ or ‘IVS-1’ and ‘IVS-2’. IVS-1 has a highly variable morphology (e.g. star-shaped, round, oval), whereas IVS-2 is tubular. The dimensions of IVS-1 vary in relation to the mesh diameters of the collagen matrix, while those of IVS-2 do not. In adult rabbit eyes, we observed transitions between IVS-1 and intravitreal ghost vessels (acellular remnants of blood vessels), and between IVS-1 and IVS-2. In very young rabbits (14 days) we observed intravitreal ghost vessels consisting of tightly-packed IVS-1. Therefore, we concluded that IVS-1 and 2 are related structures presumably of vascular origin. It appears that they represent fragmented and non-fragmented acellular remnants of hyaloid blood vessels. The presence of vascular remnants throughout the entire vitreous matrix of adult rabbit eyes is in conflict with existing theories on the embryonic development of the vitreous body, which describe a strict spatial separation between the primary (vascular) and secondary (avascular) vitreous. However, it strongly supports an alternative theory that explains the formation of the secondary vitreous by a process of continuous remodelling of the primary vitreous.

Etiology of Immune Stromal (Interstitial) Keratitis

We compared the etiologies of immune stromal keratitis (ISK), also known as interstitial keratitis (IK), in a recent group of patients with active and inactive ISK. We reviewed the charts of 97 patients seen in the cornea clinic at the University of Minnesota from 1985 through 1994. Fifty-five patients were classified as having active ISK, defined by stromal inflammation without ulceration within 1 year of presentation. Forty-two patients were identified as having inactive ISK, defined by evidence of past stromal inflammation including stromal scarring, stromal thinning, ghost vessels, and reduplication of Descemet's membrane without active inflammation for the 1 year before presentation. We determined the etiology of the ISK by careful review of the patient's ocular examination, as well as medical and laboratory workup. Patients were labeled with the diagnosis of idiopathic ISK if no identifiable etiology was found. Herpes simplex virus (HSV) accounted for 71.4% of unilateral active ISK. Idiopathic accounted for 14.3%, and varicella-zoster virus accounted for 8.6% in this group. HSV was the etiologic factor of 50.0% of inactive unilateral cases, whereas 33.3% were idiopathic. Sixty percent of cases of bilateral, active ISK were from idiopathic causes. Syphilis was the cause of 48.5% of bilateral inactive cases. In this group, 33.3% were from idiopathic causes. Although syphilis has been recognized for many years as the cause of 90% of cases of ISK, this is no longer true. We demonstrated that active ISK is most commonly caused by HSV or is idiopathic and that, although syphilis is the leading cause of inactive, bilateral ISK, it is responsible for only 18.6% of total cases.

Anin VivoModel of Human Proliferative Scar

Background.Many aspects related to the biology and the effective therapy of proliferative scars have remained undefined, in part due to a lack of an accurate and reproducible animal model with which to systematically study them. This report describes a new model for investigating the pathophysiology and manipulation of human proliferative scars.Materials and methods.Human proliferative scars (n= 86) were explanted into flaps based on isolated vascular pedicles in congenitally athymic rats. Serial analysis of the structural and functional integrity of the explanted scars was performed by microscopy and by measurement of human procollagen type III peptide (PIIIP) production, human factor VIII immunostaining, andin vitrocellular proliferation.Results.By these methods, both fibroblastic and epithelial components of explanted scar specimens retained the histologic characteristics of original human scar specimens, for up to 12 months. Over the same duration, scar explants continued to have high levels of human PIIIP, comparable to those found in original surgical specimens. The microvasculature of scar explants demonstrated a double basement membrane, with no staining of human factor VIII in the inner capillary endothelial layer, suggesting that host vessels were growing into ghost vessels of the human donor scar. Human factor VIII staining decreased over time. Fibroblasts cultured from explanted scar demonstrated less aggressive growth characteristics than those from original surgical specimens.Conclusions.This new model is the first to allow such long-term maintenance and serial evaluation of human proliferative scar on an accessible, isolated vasculature. It may prove useful in further defining the biology and therapy of this widespread pathologic process.

Glycoprotein deposition in vascular walls of diabetic retinopathy. A histopathological and immunohistochemical study.

The association between periodic acid Schiff staining and immunoreactivity to laminin, fibronectin, vitronectin, and type VI collagen was studied qualitatively and quantitatively in the retinal vascular bed from 7 eyes of 5 diabetic patients and from 5 eyes of 5 normal persons. In the retina from diabetic patients the number of arterioles showing immunoreactivity to vitronectin, the number of venules showing immunoreactivity to type VI collagen, and the number of both arterioles and venules showing immunoreactivity to laminin and fibronectin, was higher than in normals. There was no difference between the number of capillaries showing periodic acid Schiff staining and immunoreactivity to laminin, fibronectin, and vitronectin when comparing areas of vascular occlusion with adjacent control areas. However, the number of capillaries displaying immunoreactivity to type VI collagen was higher in control areas than in areas of vascular occlusion in diabetic patients and in normal controls. Staining with periodic acid Schiff correlated topographically with immunoreactivity to laminin and fibronectin, but not with immunoreactivity to vitronectin and type VI collagen. In areas of vascular occlusion there was seen no immunoreactivity or histological staining corresponding to the material accumulated to occlude the ghost vessels.

Vascular occlusion in diabetic retinopathy

The retinal vessels from seven diabetic patients and from six age-matched normal controls were studied qualitatively and quantitatively using various histological staining techniques. In diabetic patients the walls of retinal arterioles and capillaries showed significantly more staining than normals for periodic acid Schiff (neutral glycoproteins), Sirius red (connective tissue), and for Alcian blue at pH 2.6, pH 5.8 and at pH 5.8 combined with MgCl22 in concentrations less than 0.9 M (acid mucopolysaccharides). In the retina from diabetic patients there was no difference between the number of capillaries staining with these dyes in areas of vascular occlusion, and in adjacent control areas. Furthermore, in areas of vascular occlusion, the material accumulated centrally to occlude the lumen of ghost vessels did not stain with any of the dyes used. A homogenous material, accumulated in the outer retina in areas of vascular occlusion in the retina from diabetic patients, only stained with Alcian blue at pH 5.8 combined with MgCl2 in concentrations less than 0.4 M, suggesting a different molecular composition from the Alcian blue material accumulated in the retinal vascular walls. The findings are in accordance with the knowledge that basement membranes of retinal vessels are thickened in diabetes mellitus. However, the findings also indicate that basement membrane thickening cannot fully account for vascular occlusion in diabetic retinopathy.

Morphology of iris vasculopathy in exfoliation glaucoma.

Iris tissue obtained from 26 consecutive patients operated upon for exfoliation glaucoma and control iris tissue from 26 age-matched subjects operated upon for primary open angle glaucoma was used to investigate the iris vasculopathy associated with exfoliation glaucoma. By light microscopy exfoliation material was discerned by increased density of the perivascular matrix in affected vessels. By transmission electron microscopy exfoliation vasculopathy was divided into 4 grades. Grade I was characterized by focal accumulation of exfoliation material without evidence of cellular degeneration. In grade II, exfoliation material accumulation was accompanied by degeneration of vascular supporting cells; endothelial cells were unaffected. In grade III, endothelial cells exhibited degenerative changes and in grade IV, exfoliation material occupied an acellular vascular wall (ghost vessel). It is suggested that in iris vessels the synthesis of exfoliation material can be attributed primarily to the vascular supporting cells.

Laser Photocoagulation of Experimental Corneal Stromal Vascularization: Efficacy and Histopathology

Conventional treatment of corneal stromal vascularization is often inadequate. The authors developed a rabbit model of corneal stromal vascularization, treated it with laser photocoagulation, and then studied the histopathology. A reproducible model of corneal stromal vascularization was developed in albino rabbits by injecting sodium hydroxide into the corneal stroma. Corneal stromal vascularization was produced in both eyes of 13 rabbits, and treated after stabilization at 5 weeks with 577-nm yellow dye laser in 1 eye of each rabbit. Seven rabbits were followed for 6 months with corneal angiography and photography, and the corneal stromal vascularization quantified with a grid. The other 6 rabbits were killed at 1, 4, 8, 24, 48 hours, and 6 days after laser photocoagulation and examined by light and transmission electron microscopy. Stable corneal stromal vascularization was observed in the anterior and midstroma for at least 6 months in the model. Laser photocoagulation reduced corneal stromal vascularization significantly compared with the controls (P < or = 0.05), resulting in 40.7% +/- 5.0%, 45.3% +/- 3.3%, and 34.9% +/- 5.2% (mean +/- standard error of the mean) reduction at 2, 4, and 6 months, respectively. Maximum inflammatory cell infiltrates were detected at 8 hours after laser photocoagulation, which diminished markedly at 6 days. The stroma of unlasered eyes showed no inflammatory cells and considerably more patent blood vessels than the lasered eyes. In the lasered eyes, transmission electron microscopy showed damaged vascular endothelial cells, extravasated erythrocytes, haphazardly arranged collagen fibrils, thrombus formation, and ghost vessels in the stroma. No damage was observed in the deep corneal stroma or endothelium in the lasered eyes. Laser photocoagulation is effective in reducing corneal stromal vascularization in this model for at least 6 months. It does not damage the deeper stroma or endothelium.

Specular microscopy in the identification of deep corneal opacities

Specular microscopy provides a level of magnification and differentiation of detail which approaches that of a histological examination, and has the advantage of being a noninvasive procedure. This makes specular microscopy useful not only in examining the corneal endothelium, but also in identifying deep corneal opacities, which fall into two broad groups: 1) exogenous materials deposited in the cornea; and 2) endogenous pathologic corneal changes. Exogenous materials in the cornea have a wide variety of appearances, including the typical appearance of caterpillar hairs, the multifaceted appearance of glass foreign bodies, the regular geometric appearance of cholesterol crystals and cigar-shaped myeloma crystals or the more irregular deposits of chlorpromazine. Endogenous changes include ghost vessels, larger striate corneal nerves, fasciculi of fine parallel lines in keratoconus, criss-cross irregularly running lines in resolved keratitis, and a shagreen or cellophane-like appearance suggesting thickening of Descemet's membrane. While some deep corneal opacities are easily diagnosed clinically, the nature of others may be difficult to determine and specular microscopy is a valuable aid in such cases.

Differentiation of Posterior Polymorphous Dystrophy from Other Posterior Corneal Opacities by Specular Microscopy

Deep corneal opacities due to posterior polymorphous dystrophy, especially if they are mild, are frequently confused with changes due to other corneal conditions. In a series of 64 patients with deep corneal opacities (14 with Descemet's tears, 8 with posterior polymorphous dystrophy, 12 with interstitial keratitis, and 30 with keratoconus), specular microscopy enabled the differentiation of deep corneal changes provided some degree of corneal clarity was retained. The parallel “rail track” borders of old Descemet's tears were characteristic and differed from the “snail tracks” seen in posterior polymorphous dystrophy, which also showed characteristic rounded vesicular or doughnut-like lesions in Descemet's membrane. The appearances in interstitial keratitis were varied with poor detail in most cases because of corneal opacity. However, fine opacities consistent with ghost vessels were seen in interstitial keratitis and a resolving case showed fine, intersecting straight lines different from the bundles of parallel fine vertical lines of deep corneal striae in keratoconus. Specular microscopy also enables an assessment of the corneal endothelium which is important if intraocular surgery is contemplated.

Neuronal Ceroid Lipofuscinosis: A Retinal Trypsin Digest Study

Neuronal ceroid lipofuscinosis, also known as the Batten-Vogt syndrome, is clinically manifested by seizures, loss of intellect, and deterioration of vision. The retinal histopathologic and ultrastructural changes have been well-described. This report adds the findings of trypsin digest preparation of the retinae in three such patients with varying duration of this disease. Acellular retinal capillaries, or ghost vessels, were observed, and the degree of this change correlated with the duration of clinical symptoms. These changes, as well as the histopathologic abnormalities, are discussed.

Talc Emboli and Macular Ischemia in Intravenous Drug Abuse

A patient with decreased visual acuity had small, glistening white particles that were scattered over both posterior poles. Monochromatic fundus photography revealed ghost vessels and intraluminal particulate matter in small retinal vessels. Fluorescein angiography demonstrated nonperfusion of small arterioles and macular capillaries. The patient admitted to multiple intravenous injections of crushed methylphenidate (Ritalin) hydrochloride tablets, which contain talc 18 months prior to examination. To our knowledge, visual loss and irreversible macular ischemia from talc emboli have not been previously documented.