Ophthalmology consultation in the diagnosis and treatment of sarcoidosis.

We reviewed 204 cases of biopsy-proved sarcoidosis at our institution from 1967 through 1983 to determine the extent of this disease in our catchment area and the degree of awareness by the various medical specialties of sarcoid manifestations. The ophthalmology service was used as an example. Our results showed that there were familial clusters of sarcoid; that one half of the patients born in the United States were from the southeast; that the mode of initial presentation varied considerably; and that only 44% of patients were referred to an ophthalmologist even though more than one half of those examined by an eye doctor manifested signs and symptoms of ocular sarcoidosis. We advocate a more cooperative interdisciplinary approach to the diagnosis and treatment of sarcoidosis because of its broad spectrum of clinical manifestations.

RPE destruction causes choriocapillary atrophy.

The authors have obtained evidence that destruction of the retinal pigment epithelium (RPE) causes choriocapillaris (CC) atrophy. The observations led us to hypothesize that the RPE modulates CC structure and function. Rabbits received injections of sodium iodate, which selectively destroyed the RPE. The authors killed the rabbits at various times after iodate and examined the RPE and CC by fluorescein angiography, fundus photography, and light and electron microscopy. Fluorescein angiography and fundus photography revealed a pattern of retinopathy similar to that described by other investigators, eg, blood-retinal barrier breakdown and the patchy nature of the RPE/CC degeneration. One week after injection of iodate, the RPE transformed into a mixture of flattened, depigmented cells and plump, highly pigmented ones lying along Bruch's membrane. The CC appeared normal by light microscopy, but electron microscopy revealed changes indicating CC atrophy: degenerating endothelial cells (EC), EC that appeared normal but had reduced numbers of fenestrae, and pericapillary basal laminae that looped away from the endothelium, as if the latter had shrunk. One month after iodate, patches of Bruch's membrane were devoid of RPE, which was replaced by scar tissue. The CC was markedly atrophic over these patches, having reduced numbers of profiles and smaller lumina in those which remained. The CC appeared normal over areas where RPE remained. Eleven weeks after iodate, the light microscopic picture parallelled that seen 1 month after injection, but the patchy RPE degeneration was more extensive. By electron microscopy, the CC profiles over areas devoid of RPE showed severe atrophy. Degenerating EC were more numerous. EC adjacent to areas of RPE loss had few or no fenestrae. Here, capillaries were encased in dense, collagenous, connective tissue, unlike the CC of normal rabbits. These changes were not seen where the RPE still covered Bruch's membrane. These observations suggest that RPE modulates CC structure and function. The authors propose that a diffusible vascular modulating factor produced by RPE cells does this.

Vascular permeability and the optic disc. Changes after bilateral common carotid ligation in the rat.

The permeability of retinal blood vessels to intravenously injected horseradish peroxidase was examined two to seven days after bilateral common carotid ligation in rats. Light and electron microscopy revealed leakage from the blood vessels of the optic disc. This leakage appeared to result from vesicular transport across the endothelium; the interendothelial tight junctions we examined remained intact and there was no evidence of endothelial cell death. The intraretinal blood vessels and the retinal pigment epithelium retained their normal impermeability to horseradish peroxidase. Cellular edema was present at the optic disc, manifested as swollen axons. Glial cells remained normal in appearance and the extracellular space was not enlarged. These observations clarify those previously derived from funduscopy and fluorescein angiography, which revealed disc edema and hyperfluorescence.

Retinal arterial occlusive disease in systemic lupus erythematosus.

Four patients with systemic lupus erythematosus (SLE) developed an unusual form of occlusive retinal arterial disease. The most prominent clinical features of this disorder were deposition of yellow-white material in retinal arterial walls and evidence of multifocal retinal arterial occlusion. Fluorescein angiographic findings included nonperfusion of the obstructed arteries and the retinal capillary beds fed by them, and fluorescein leakage at the sites of involvement of the retinal arteries. This ocular complication of SLE is presumably a manifestation of the widespread systemic vascular problems seen in this disorder. It may be more common in patients with lupus involving the CNS.

Ultrastructure of Bruch's membrane after krypton laser photocoagulation. I. Breakdown of Bruch's membrane.

Previous observations on rats suggested that subretinal neovascularization does not require a prior break in Bruch's membrane (BM). We verified this observation by using scanning electron microscopy to examine large expanses of BM that became exposed following ophthalmoscopically white krypton laser burns. Bruch's membrane appeared intact in the acute phase after injury. Subsequently, slitlike defects in BM were associated with penetrating choroidal capillaries. These observations were consistent with transmission electron microscopic findings of cellular protrusions arising from the choriocapillary endothelial cells and from regenerating retinal pigment epithelial (RPE) cells invading BM. These cell-formed defects in BM differed from thermal defects in appearance, size, and onset of occurrence. Endothelial cells penetrated all layers of BM, including the RPE basement membrane. We conclude that endothelial cells can erode their own basement membrane and the RPE basement membrane, and krypton laser burns with or without immediate rupture of BM induce cellular activity that may result in defects in BM.

Ultrastructure of Bruch's membrane after krypton laser photocoagulation. II. Repair of Bruch's membrane and the role of macrophages.

The accompanying ultrastructural study showed that ophthalmoscopically white krypton laser photocoagulation in rats is followed by cellular invasion causing breakdown of Bruch's membrane (BM). We have expanded these observations, using scanning electron microscopy, transmission electron microscopy, and high-voltage transmission electron microscopy to describe the healing process. The repair of BM involves regenerating retinal pigment epithelial cells and choriocapillaris (CC) that form new basement membranes and fibroblasts that secrete collagen and elastin. The reformation of the CC is also associated with subretinal neovascularization. The involvement of macrophages was evident throughout the process of BM repair and formation of new vessels. We propose that the macrophages act as a common factor linking the diverse diseases associated with choroidal subretinal neovascularization, deduced from our evaluation of the healing process and the reformation of choriocapillaris.

Fluorescein angiographic patterns of iris melanocytic tumors.

Iris fluorescein angiography was performed on 23 patients with primary iris melanocytic tumors. Four angiographic patterns were identified, the first three of which were considered to be usually indicative of a benign lesion, based on clinical duration and follow-up, biopsy specimens, and stable patterns on repeated angiography. (1) Eleven moderately to heavily pigmented placoid lesions were angiographically silent, in that they failed to display either a tumor-associated vasculature or diffuse leakage. (2) Seven generally nonpigmented lesions demonstrated a quasi-geometric filigree vascular network, approximating the caliber of the normal radial vasculature. These tumor-associated vessels fluoresced early and in synchrony with the appearance of dye in the radial vasculature from which they probably were derived, but they diffusely and confluently leaked fluorescein in the late phases of the angiogram. (3) Three brown or variably pigmented lesions manifested a mixed angiographic pattern, combining features of groups 1 and 2. (4) The final angiographic pattern was comprised of two pathologically proved mixed spindle-epithelioid cell melanomas, each of which in part or in toto showed diffuse and eventually confluent fluorescence emanating from ill-defined vascular foci. One of these two lesions additionally exhibited a large area that was perfused late by irregular leashes of vessels. The ability to distinguish benign from malignant melanocytic lesions of the iris can be greatly enhanced by iris fluorescein angiography.

Bilateral total corneal and conjunctival choristomas associated with epidermal nevus.

A 4-year-old boy had been noted from birth to have bilateral masses obscuring the entire outer portion of the eyes. Systemic findings included mild growth retardation, multiple cortical lesions of the distal metaphyseal ends of the lower extremities, and diffuse skin pigmentation of the right side of the body. The epibulbar lesions were excised; on the right side, there was a thin cornea that necessitated corneal transplantation. The diagnosis of composite epibulbar choristomas associated with linear epidermal nevus was established by pathologic examination. This case report as well as a literature review establish the association of epibulbar choristomas with cutaneous linear nevi of the epidermal and sebaceous types.

Bilateral corneal dermis-like choristomas; an X chromosome-linked disorder.

A male child was born with bilateral corneal opacification. His maternal uncle and a male first cousin of the patient's mother also had been born with identical bilateral corneal opacification that was pathologically proven to result from corneal dermoids. Histopathological examination of tissue removed from the present patient at the time of lamellar keratoplasty revealed thickened, keratinized epithelium, absent Bowman's membrane, and dense, irregular bands of highly vascularized collagenous connective tissue. No adnexal appendages were identified. The remainder of the ocular and general physical examination results was normal. In view of these clinical and histopathological similarities, the diagnosis of corneal dermis-like choristomas was made. To our knowledge, this report is the first to describe a family with X chromosome-linked recessive transmission of this condition.

Neovascularization of the iris (rubeosis iridis).

This is a review of neovascularization of the iris and the neovascular glaucoma that often follows. With the aging of our population, this has become a more frequent cause of blindness and enucleation of eyes. Iris neovascularization is never primary, but is always secondary to other ocular disorders. The pathology is described based on the study of 110 globes. Diagnosis, pathogenesis and treatment are discussed.

Visual system involvement in giant cell (temporal) arteritis.

A case of giant cell arteritis is reported. The presenting complaint was referable to the vertebral-basilar system. Visual symptoms and signs of vertebral-basilar, carotid, posterior ciliary, and branch central retinal arterial involvement are described. Blindness occurred on steroid therapy. Death resulted from steroid complications. The wide clinical spectrum and management of this condition are discussed.

Chemosis, proptosis and amaurosis in a 19-year-old male.

An ectopic pinealoma was excised in 1966 and the patient received radiotherapy postoperatively. The patient developed diabeted insipidus, hypopituitarism, chemosis, proptosis, and loss of vision in the left eye. The left eye was enucleated in 1974 and a large orbital mass was found to contain malignant cells consistent with the diagnosis of germinoma. The orbital mass was in all likelihood a metastasis from the original focus of the tumor.

Multiple myeloma and its ocular manifestations.

Multiple myeloma is a malignancy of the cells of the immune system that frequently involves the eye. Cysts of the ciliary body have been reported in 33-50% of myeloma patients, and retinal vascular lesions have been reported in up to 66%. Corneal and orbital involvement is less common. In this review, systemic and immunologic aspects of multiple myeloma are outlined and ocular manifestations are illustrated.

Downbeat nystagmus.

A patient with downbeating nystagmus in the primary position and vertical saccadic pursuit is presented. The possible etiologies of these features and their diagnostic significance is discussed.

Ocular neovascularization. The Krill memorial lecture.

The various vascular systems of the eye can undergo new vessel formation. In this presentation, I discuss new vessel growth in the cornea, lens, iris, ciliary body, choroid, retina, and optic nerve head. No single factor can explain all cases of ocular neovascularization; instead there are multiple factors which can affect the various susceptible vessels. Among the known vasculognic factors are: inflammation and its products, a hypoxic retina diffusable factor, the "tumor angiogenic factor," and possibly an aging factor. The different ocular beds possess differing sensitivity to the various vasculogenic stimuli; the iris and choroid being most sensitive and the retina and ciliary body least sensitive to such stimuli. Retinal neovascularization requires both a biochemical factor and a diseased retinal vascular bed for its induction. Ocular neovascularization is a dynamic process which requires a persisting stimulus or else the new vessels tend to regress. The normal eye seems to possess at least two antivasculogenic agents.

Progressive external ophthalmoplegia and benign retinal pigmentation.

A 17-year-old boy had progressive external ophthalmoplegia, normal visual acuity, and a pigmentary retinopathy. Neurologic evaluation showed an abnormal electroencephalogram with diffuse slow (theta) waves. Myasthenia gravis was excluded. Fluorescein angiography showed a normal vascular pattern with diffuse hyper- and hypopigmentation. Results of retinal testing, including color vision, visual fields, electroretinography, and dark adaptometry, were within normal limits except for a slightly subnormal electroretinogram with normal implicit times. Progressive external ophthalmoplegia may be associated with either progressive or non-progressive pigmentary retinopathies, and adequate evaluation of retinal function in these cases must be obtained.

Ocular findings in the facioauriculovertebral sequence (Goldenhar-Gorlin syndrome).

We reviewed the ocular findings in 57 consecutive patients with the facioauriculovertebral sequence (Goldenhar-Gorlin syndrome). Epibulbar choristomas were detected in 18 cases (32%), a much lower occurrence than reported previously. Various motility disorders (11 cases, 19%), blepharoptosis or narrow palpebral fissures (seven cases, 12%), eyelid colobomas (six cases, 11%), and lacrimal drainage system anomalies (six cases, 11%) were more frequent than previously noted. These ocular findings were more common in the patients with epibulbar choristomas. Of the various features of the Goldenhar-Gorlin syndrome (skin tags, microtia, hemifacial microsomia, and vertebral anomalies), only skin tags correlated positively with the laterality of epibulbar choristomas. Preauricular and facial tags represent choristomas, explaining their association with epibulbar choristomas and the laterality they share.

Momentary fluctuations of intraocular pressure in normal and glaucomatous eyes.

To examine the range of momentary fluctuations of intraocular pressure caused by vascular pulsations in 42 glaucomatous and 18 normal eyes, we obtained consecutive intraocular pressure measurements at hourly intervals with a noncontact air tonometer. Glaucomatous eyes had a significantly (P less than .001) greater range of intraocular pressure measurements on consecutive readings than normal eyes (4.4 +/- 1.4 mm Hg vs 2.7 +/- 0.7 mm Hg). The frequency of consecutive intraocular pressure readings exceeding a spread of 4 mm Hg was significantly increased in glaucomatous eyes. The range of intraocular pressure measurements was greater even in those glaucomatous eyes with mean intraocular pressures within the normal range. There was a positive correlation between mean intraocular pressure and mean range in glaucomatous eyes, but not in normal eyes. In both glaucomatous and normal eyes, there was no significant correlation between age and mean range.

Ultrastructure and clinicopathologic correlation of idiopathic preretinal macular fibrosis.

Detailed light and electron microscopic examination of early idiopathic preretinal fibrosis lesions showed that the fibrosis consisted of a layer of glial cells on the retinal surface. Two cases supported the clinical observation that a glinting retinal reflex preceded the development of retinal folds and traction lines. In both cases there was a break in the inner limiting lamina through which glial cells migrated and, presumably, proliferated on the retinal surface. There was no evidence for vitreoretinal adhesions. The ultrastructural similarity of the lesion to preretinal glial membranes seen in other disease entities suggested the possibility of a common biochemical stimulus for glial cell migration and proliferation on the retinal surface.

Schwann cell proliferations mimicking medullated retinal nerve fibers.

Ophthalmoscopically visible white patches in the optic nerve head and adjacent retina in a rhesus monkey histologically represented peripheral rather than central nervous myelin. This case of Schwann cell proliferations appearing as medullated retinal nerve fibers raises questions concerning the relationship of this phenomenon to developmental and acquired lesions of the optic nerve head in man.