Adult-onset foveomacular vitelliform dystrophy and indocyanine green videoangiography

Background Adult-onset foveomacular vitelliform dystrophy (AOFVD) represents a heterogeneous group of disorders with different clinical, angiography, and histopathological features. The most common form is characterized by a yellow, round to oval subretinal macular lesion with or without central pigmented spot. Methods Eight patients affected by typical AOFVD underwent fluorescein an giography and indocyanine green videoangiography (ICGV). Results Fluorescein angiography showed a central hypofluorescent spot surrounded by an irregular hyperfluorescentring ICGV demonstrated a foveal nonfluorescent spot, visible during the entire examination, and a hyperfluorescent area surrounding the central spot, which became evident soon after the beginning of the examination. Conclusions In light of previous histopathological studies, the central nonfluorescent spot may be interpreted as a masking effect of a pigment clump, whereas the hyper-fluorescent area may represent dye pooling or staining of the subretinal pigment epithelial material.     

Precision of ultrasonic estimates of choroidal melanoma regression

Background: Important prognostic information may be gained from knowledge of the volume and, over time, the change in volume of intraocular tumours such as choroidal melanomas. Methods: The precision and time consumption of three different ultrasonographic methods were evaluated. Seven choroidal melanomas were analysed after placement of a ruthenium plaque and again after tumour regression had occurred. Perpendicular ultrasound B-scans were printed and analysed by overlay grid counting or outline tracing of tumour structures to calculate the volume. These two methods, using only two perpendicular scans, were compared with a micro-computer-controlled ultrasonographic three-dimensional rotation scanning system, where each tumour was manually outlined in 20 revolving scan planes. Results: The three-dimensional volume scanning method was the most precise, but also the most demanding in hardware and time consumption. Conclusion: Increased precision and less observer-dependent estimation of shrinkage rate after radiotherapy is available at the cost of sophisticated equipment.     

Expression of vascular endothelial growth factor in experimental choroidal neovascularization

Background: Although the choroidal neovascularization (CNV) is a common pathologic feature of a number of different eye diseases, its pathological mechanisms have not been fully elucidated. We investigated the expression of vascular endothelial growth factor (VEGF) in CNV using an experimental primate model. Method: CNV was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 1, 3, 7 or 14 days after photocoagulation and examined immunohistochemically for VEGF, macrophage antigen, von Willebrand factor and glial fibrillary acidic protein (GFAP). Expression of VEGF mRNA was examined byin situ hybridization. Results: One day after photocoagulation, the normal structure of the outer portion of the retina and the inner portion of the choroid was destroyed. Three days after photocoagulation, choroidal vascular endothelial cells migrated into the subretinal space through the defect in Bruch's membrane. Increased expression of VEGF was detected in the accumulating macrophages, migrating retinal pigment epithelial (RPE) cells and Muller cells. Maximal expression of VEGF was observed between 3 and 7 days after wounding, and many newly formed vessels extended into the subretinal space 7–14 days after photocoagulation. Conclusion: VEGF derived from RPE cells, macrophages and Müller cells may play a role in the formation of CNV.     

Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration

Background: The morphological features of angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration are yet to be fully described. Methods: Six eyes from five patients which on clinical and histological examination showed advanced age-related macular degeneration and early choroidal neovascularization have been studied by transmission electron microscopy. Results: Pre-existing choroidal capillaries and venules showed changes which included endothelial cell budding, pericyte enlargement, endothelial cell sprout formation and the development of intrachoroidal new vessels. In one case, an endothelial cell sprout continuous with an intrachoroidal vessel penetrated Bruch's membrane. Examination of early subretinal pigment epithelial new vessels showed them to spread between the inner layers of Bruch's membrane within the space usually occupied by the basal linear deposit and drusen. New vessel formation took place in blind pouches at the margins of new vessel networks, either in the absence of pericytes or in the presence of mainly myofibroblast-like pericytes. Conclusion: This ultrastructural study describes two phases of new vessel growth associated with the onset of choroidal neovascularization secondary to age-related macular degeneration. The initial intrachoroidal phase appears to be a low-turnover form of neovascularization which may lead to new vessels penetrating Bruch's membrane. Extensive subretinal pigment epithelial neovascularization, on the other hand, results from a high-turnover phase of neovascularization characterized by extensive endothelial cell proliferation and migration. Pericyte phenotypic changes associated with these different phases of neovascularization appear to relate to the dynamics of angiogenesis taking place in each process.     

Indocyanine green angiography in choroidal osteoma

Background: Choroidal osteoma is a rare choroidal tumor; knowledge of its indocyanine green characteristics is limited. Methods: The fundus photographs and the fluorescein and indocyanine green angiograms of three patients were reviewed. Each patient was examined at least twice with a follow-up varying from 10 to 60 months. Results: Latephase fluorescein angiograms allow assessment of the extension of the osteoma as it is variably hyperfluorescent due to tumor staining combined with a variable degree of overlying retinal pigment epithelial changes. The hypofluorescent area observed in the early phase of the indocyanine green angiogram corresponds with the extent of the osteoma but the borders may be difficult to demarcate. In the late phase of the indocyanine green angiogram, hypofluorescence due to choriocapillaris loss and hyperfluorescence due to leakage from abnormal choroidal vessels are combined. Infrared angiography highlights abnormal choroidal vessels and vascular spiders present on the tumor surface. It is difficult to differentiate these choroidal vascular anomalies from subretinal neovascularization. Conclusion: We find no homogeneous pattern either on fluorescein or on infrared angiography. The findings may change with follow-up, indicating changes within the tumor or the surrounding tissue that are still poorly understood.This work was presented at the fourth meeting of the European Macula Group, 31 May 1996, Genoa, Italy     

Indocyanine green angiography of choroidal tumors

Background: Fluorescein angiography (FA) has been widely used in the diagnostic evaluation of cboroidal tumors. Indocyanine green angiography (ICG-A), which permits better visualization of choroidal vasculature than FA, has been recently introduced into clinical practice. Only few reports exist on the ICG-A characteristics of choroidal tumors. Methods: The fluorescein and indocyanine green angiograms of 61 patients were assessed. These included 14 patients with choroidal nevi, 30 with malignant melanomas, 7 with suspected melanomas or atypical nevi, 5 with hemangiomas and 5 with metastases. Results: The outline of pigmented tumors was more accurate on ICG-A than on FA. Characteristic patterns were seen in all intra-ocular tumors with ICG-A, so it was possible to distinguish hemangiomas from malignant lesions. Characteristic features of malignant melanomas include abnormal vascular pattern and marginal late dye leakage. None of the benign lesions showed these features. In suspected melanomas, the presence of abnormal choroidal vascular patterns and/or late dye leakage on ICG-A may indicate malignancy. Conclusion: The study suggests that ICG-A can yield additional information that is useful in differentiating amongst choroidal tumors. Better delineation of pigmented lesions with ICG-A allows more accurate treatment planning and follow-up.     

Ophthalmological and neuro-ophthalmological involvement in Churg-Strauss syndrome: a case report

Background: It is well known that different types of eye involvement may develop during the course of systemic vasculitides. Methods: We report here a case of Churg-Strauss syndrome (allergic granulomatous angiitis) characterized by the presence of multiple ophthalmological and neuro-ophthalmological lesions, i.e., mononeuritis of the fourth cranial nerve, multifocal choroidal ischaemia, and bilateral ischaemic optic neuropathy. Results: Ischaemic lesions in the posterior ciliary plexus and chorio-retinal circulation, which appeared simultaneously after a phase of disease activity, were documented. Conclusion: The simultaneous occurrence of multiple ocular features in a patient with Churg-Strauss syndrome suggests that regional vasculitis may be the pathological mechanism underlying the multiple ophthalmological lesions in this disorder.     

Choroidal metastasis of mixed carcinoma of the parotid gland

Background: A case of mixed carcinoma of the parotid gland (an epidermoid carcinoma located in a pleomorphic adenoma) metastatic to the choroid is presented. The histopathology of the tumor is discussed. Methods: A 65-year-old man was admitted complaining of blurred vision in his right eye for 1 day. He underwent parotidectomy for mixed carcinoma of the parotid gland (an epidermoid carcinoma located in a pleomorphic adenoma that was completely excised) 6 months before. Funduscopic examination showed a nasal retinal detachment, with gray-whitish, minimally elevated nodular choroidal lesions. Fluorescein angiography and contact B-scan ultrasonography confirmed the presence of an underlying mass. Results: The right eye was enucleated and an epidermoid infiltrating carcinoma was identified. Conclusions: Metastatic tumors are the most common intraocular malignancies, and the choroid is by far the most common location for intraocular metastases. There are few cases reported of parotid tumors metastatic to the orbit. To the best of our knowledge, no histological examination of an ocular metastatic mixed carcinoma of the parotid gland has yet been reported.     

The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary angle closure glaucoma

Background: The present study was performed to investigate the ultrastructure of deep retinal layers and choroid corresponding to the parapapillary chorioretinal atrophy in eyes with secondary angle-closure glaucoma. Methods: The glaucomatous eyes included two eyes enucleated due to iris ring melanoma with high intraocular pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The control eyes included one eye enucleated due to choroidal malignant melanoma with normal intraocular pressure and one eye enucleated during surgery for supramandibular carcinoma. These eyes were studied with light and electron microscopy. Results: In the region of parapapillary chorioretinal atrophy of glaucomatous eyes, the retinal pigment epithelial cells showed degenerative changes, such as loss of basal in foldings and microvilli, degenerated mitochondria, vacuolar degeneration and irregular distribution of melanin granules. The photoreceptors were decreased in number in this area of glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic nerve was collapsed. Conclusion: These results elucidate the fine structures of deep retina and choroid in the region of parapapillary chorioretinal atrophy of glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy.     

Hemodynamic parameter estimation from ocular fluorescein angiograms

Background: A method is proposed for parameterizing choroidal blood flow from fluorescein angiograms. Methods: After digitizing and aligning the angiographic sequence, the intensity build-up curves of fluorescence are analysed per pixel (approx. 10 m in fundo). Two models are compared. A one-compartment model predicts an exponential build-up curve, from which the following parameters are estimated: maximum fluorescence, dye appearance time and local perfusion rate (reciprocal of the time constant of the exponential). To account for the contribution of the systemic circulation to the shape of the build-up curve, a two-compartment model is used which predicts a bi-exponential curve. Results: Introduction of the second (systemic) compartment resulted in a significant improvement of fit in 37 of 48 patients studied. The rate constants of the systemic compartment found were mainly in the range of 0.30–1.00 s^–1. Conclusion: For the individual patient, the local perfusion rates may vary strongly, with lower perfusion rates possibly being of prognostic value for ocular diseases such as glaucoma or diabetic retinopathy.     

The use of tissue plasminogen activator in post-traumatic total hyphaema

Background: We wanted to evaluate whether intracameral injection of tissue plasminogen activator (tPA) is useful in managing traumatic hyphaema. Methods: Two eyes with total hyphaema after a severe penetrating injury were treated with a single intracameral injection of 25 g of tPA 5 and 14 days after the injury, respectively. Results: Most of the blood coagulum dissolved within 24 h, and in one of the two eyes the intraocular pressure decreased from 45 to 8 mmHg. The other eye was hypotonic. No re-bleeding or complications related to the use of tPA were noticed. Conclusion: The results in these two cases suggest that tPA is a useful adjunct in managing total hyphaema.     

CD44 expression in the developing human retina

Background: CD44, the transmembrane adhesion molecule, is expressed in the fetal brain and supposed to mediate neuroglial interactions. We evaluated the expression and distribution of CD44 in the developing human retina. Methods: Four developing human eyes were evaluated at 6, 10, 16, and 21 weeks of gestation, as well as the eyes of one infant and four adults. Frozen sections were immunohistochemically stained with monoclonal antibodies to three human CD44 clones (BU52, F10-44-2, and DF1485) and to vimentin, and antiserum to glial fibrillary acidic protein (GFAP). Specimens were evaluated by light and electron microscopy. Results: Positive immunostaining for CD44 was first detected at 21 weeks of gestation in the longitudinal fibers that extended from the inner to the outer limiting membrane and around capillary vessels with the simultaneous expression of vimentin and GFAP. Immunoelectron microscopy demonstrated the presence of CD44 on the surface of Müller cells and astrocytes. CD44 was faintly seen in the Müller cells in the periphery and definitely present in the astrocytes in the infant and adult retinas. Conclusion: CD44 was expressed in Müller cells at a late stage of fetal development and in the fetal, infant, and adult astrocytes, which suggests that it is important in the morphogenesis and homeostasis of the neural retina.     

Silent myocardial ischemia in glaucoma and cataract patients

Background: Glaucoma and cataract are multifactorial diseases. They have been described to be associated with cardiovascular risk factors. Methods: Twentyfour-hour ECG monitoring was done in 22 normal-tension glaucoma patients, 27 open-angle glaucoma patients, 25 cataract patients, and 20 normal controls. The frequency of silent myocardial ischemia (SMI) as well as that of ventricular extrasystoles (VES) was evaluated. Results: At least one episode of significant asymptomatic ST-T segment depression occurred in 45% of the normal-tension glaucomas, in 25.9% of open-angle glaucomas, in 12% of cataract patients, and in 5% of normal controls. The frequency of VES was not significantly different among the groups. Conclusions: Glaucoma, especially normal-tension glaucoma, is significantly associated with the occurrence of episodic asymptomatic myocardial ischemias. Cataract patients, however, had only a slightly, statistically not significantly increased frequency of both SMI and VES compared with normals.     

Orbital exenteration: Surgical and reconstructive strategies

Background: Radical exenteration procedures, which include the removal of orbital content and eyelids, result in serious functional limitations, especially with respect to eating and speaking. Therefore we have recently changed our surgical concept. Methods: Seventy-seven patients underwent orbital exenteration during the 20-year period from 1974 to 1995 at the Department of Maxillofacial Surgery, Essen University. The simultaneous removal of periorbital bone was performed in 45 of these cases. Results: The 1-year survival rate was 89%, the 5-year rate was 63% and the 10-year rate was 48%. The surgical approach, the amount of resected orbital tissue and the reconstructive procedure have been adapted to the individual needs, depending on the location and extent of the tumor. Subsequently, the surgical morbidity has decreased. Discussion: Detailed consideration of all clinical and histological findings is essential before surgery, in order to prevent a higher rate of recurrence following these modified operations.     

Effect of corticosteroids on healing of the corneal endothelium in cats

Background: Anterior segment surgery is frequently complicated by damage to the corneal endothelium. We examined the effects of corticosteroids, which are widely used for the suppression of postoperative inflammation, on the process of endothelial cell regeneration. Methods: The effect of corticosteroids on healing of the corneal endothelium was examined in 10 domestic cats. In both eyes a circular area, 8 mm in diameter, was scraped off at the center of the corneal endothelium without damaging Descemet's membrane. Immediately after scraping, as well as 2 and 5 days later, each animal received a unilateral retrobulbar injection of betamethasone sodium phosphate (2 mg). The other eye served as a control and received a retrobulbar injection of the vehicle only. Results: Evaluation of the corneal endothelium 2, 5 and 7 days after the trauma revealed that relative to the control contralateral eyes, the corticosteroid-treated eyes exhibited a higher mean coefficient of variation of the corneal endothelium cell area, fewer hexagonal cells, a larger number of polygonal cells with 3, 4, 7 and 8 cellular facets, thinner corneas and less inflammation. Conclusions: These findings suggest that corticosteroids unfavorably affect the regeneration of corneal endothelial cells after injury. As corticosteroids appear to have both positive and adverse effects on corneal function after trauma, they should be used with caution.     

Corneal neovascularization in rats as a model for photothrombotic therapy using bacteriochlorin a and an argon laser

Background: The presence of vessels has a negative influence on corneal transplant survival. Closure of such vessels prior to transplantation may improve the transplant results, and this might be achieved by irradiating the vessels with argon laser light after intravenous administration of a photosensitizer, e.g. bacteriochlorin a (BCA). A suture-induced corneal neovascularization model in rats was set up to test this hypothesis. Methods: Suture-induced vessels in the cornea of male Wistar rats were irradiated with argon laser light after intravenous administration of BCA. We applied irradiation of varying energy levels and duration and assessed the changes in the vessels by slit-lamp examination, fluorescein angiography and histology. Results: Suture-induced corneal vessels in the rat could be used effectively to study photothrombosis therapy. Intravenous administration of BCA prior to irradiation (=514.5 nm) of the corneal vessels led to vessel closure at lower energy levels and of longer duration than occurred with laser treatment alone. Conclusion: Suture-induced corneal neovascularization in the rat can be used as a model to study the efficacy of photothrombosis therapy. BCA can be used to enhance the rate and duration of vessel closure.     

Fundus pulsation measurements in diabetic retinopathy

Background: There is experimental evidence that retinal blood flow is impaired in patients with diabetes mellitus. Much less attention has been paid to choroidal blood flow. Hence it was the aim of the present study to investigate choroidal blood flow in diabetic retinopathy. Methods: A new noninvasive laser interferometric technique was used to measure fundus pulsations in the macula. The fundus pulsation amplitude, which is the maximum distance change between cornea and retina during the cardiac cycle, is a measure of local pulsatile blood flow. The eyes (n = 214) were divided into four groups according to the modified Airlie House classification: (1) no retinopathy (control group), (2) background retinopathy, (3) moderate to severe preproliferative retinopathy, (4) proliferative retinopathy. In 83 eyes of different groups fundus pulsation measurements were repeated after 1–6 weeks. Results: Fundus pulsation amplitudes were significantly smaller in group 4 than in the control group (P < 0.027). The reproducibility of the measurements was high and did not differ among the study groups. Conclusions: Local fundus pulsations in the macula are reduced in proliferative diabetic retinopathy, which is compatible with previous findings of reduced choroidal blood flow in late stages of the disease. Laser interferometric measurement of fundus pulsations is non-contactile, assures optimal comfort for the patient and could be used for the long-term observation of patients with diabetes mellitus.     

Serum-induced collagen gel contraction

Purpose: To understand the molecular events underlying disease-related vitreous gel contraction, the effect of serum components on collagen was investigated. Methods: Bovine vitreous or dermal collagen was incubated with a mixture of transglutaminase (TG; factor XIIIa) and fibronectin (FN), and the biochemical changes of collagen were monitored by gel electrophoresis. In addition, serum-induced changes in the volume of the collagen gel were monitored. Results: Gel electrophoresis revealed a new high-molecular-weight band (M_r 240 000) presumably due to intermolecular cross-links of collagen peptides and FN. The serum components also were shown to cause a significant decrease in the volume of the collagen gel. Conclusion. Collagen gel contraction could be attributed to the collagen-FN-collagen cross-links catalyzed by TG.     

Visualization of retinal and choroidal blood flow with fluorescein leukocyte angiography in rabbits

Purpose: To visualize the retinal and choroidal leukocytes in rabbits with a new technique, fluorescein leukocyte angiography using a scanning laser ophthalmoscope. Methods: Blood was withdrawn from an ear vein of a rabbit (New Zealand White), mixed with fluorescein dye in a test tube and centrifuged. The yellow-brown coat layer containing fluorescein-stained leukocytes was collected and injected into the ear vein of the same rabbit while performing fluorescein angiography with a scanning laser ophthalmoscope. The angiographic image displaying circulating fluorescent leukocytes in retinal and choroidal vessels was recorded on a videotape. Results: Fluorescent leukocytes were clearly visible in the retinal arteries, capillaries, veins and choroidal vessels for more than 1 h. Plugging of leukocytes was seen throughout this period of time in choroidal vessels, while plugging was rare in retinal vessels. Conclusions: Fluorescein leukocyte angiography is a new technique which can be used for visualization of the leukocytes in retinal and choroidal vessels non-invasively and in vivo.Presented in part at the 5th International Meeting on Scanning Laser Ophthalmoscopy, Tomography, and Microscope, San Antonio, Texas, 26–28 October 1995; Presented as a video presentation at the 76th meeting of the Korean Association of Ophthalmology (Seoul, 15–16 May 1996     

Detection of herpes simplex virus after penetrating keratoplasty by polymerase chain reaction: correlation of clinical and laboratory findings

Background: The study was carried out to investigate the possible correlation of clinical findings, histopathologic features and detection of herpes simplex virus DNA in corneal buttons obtained after penetrating keratoplasty. Methods: We examined 47 consecutive corneal buttons sent for histopathologic examination by light microscopy and using the polymerase chain reaction for the detection of HSV1 and HSV2. Twenty-one corneal buttons from eyes with bullous keratopathy served as controls. Results: The 47 cases were graded from the clinical information available as unproven, suspected and clinically proven cases of herpetic keratitis. This grading did not correlate to specific histopathologic features or to the results of HSV1 DNA testing. None of the cases were positive for HSV2 DNA. Conclusion: HSV DNA was detected in some of the cases of clinically unsuspected herpetic keratitis. This technique of demonstrating the presence or absence of HSV in the cornea after keratoplasty is more reliable than clinical data or histopathologic findings and may be important in cases of recurrent inflammatory episodes involving grafts after keratoplasty.Presented in part at the meeting Frontiers in Penetrating Keratoplasty on 22 September 1994, Heidelberg, Germany