Corneal calcification.

Superficial calcification was produced in the normal rabbit cornea by mild irradiation with a carbon dioxide laser. The calcification was entirely extracellular and closely resemnbled that observed in human band keratopathy, which was characterized as hydroxyapatite by x-ray diffraction. The electron-mnicroscopic appearance of calcific spheriules and conglomerates in early cornteal calcification is presented. The calcific spherules arise at the basal plasma membrane surface of the epithelial cells in close relation to their basement membrane.

Repair and late degeneration of the primate foveola after injury by argon laser.

Each foveola of nine rhesus monkey eyes was subjected to a single, mild, calibrated exposure from an argon laser (1 to 1.4 mW for 10 to 20 min). Observations from ophthalmoscopy, fundus photography, and fluorescein angiography were correlated with light and electron microscopic studies. The ophthalmoscopic changes consisted of initial whitening and subsequent but persistent depigmentation of the foveola. Fluorescein angiography showed a pattern consistent with "window defect" of the retinal pigment epithelium (RPE). In the first 6 months after injury, the pathologic changes consisted of initial vacuolar changes of the RPE, followed by persistent hypopigmentation and slow development of membranous bodies or lipoidal degeneration in these cells. Initial alteration and subsequent incomplete reformation of cone outer segments were also noted. In animals sacrificed 3 to 4 years after injury, separation of RPE from Bruch's membrane, with production of various abnormal basement membranes and intercellular cystoid changes in the overlying retina, was observed. The morphologic observations suggest that although the mildly injured epithelial cells may recover, they may develop functional incompetence at a later date, resulting in serous detachment of RPE and foveal (macular) edema.

Pigment epithelial windows and drusen: an animal model.

Aging rhesus monkeys, both controls and those undergoing long-term administration of investigational oral contraceptive steroids, developed widespread hyperfluorescent dots at the posterior pole. The dots were considered to represent drusen. Histologic (including electron microscopic) study showed the "drusen" in some of the animals to be almost exclusively pigment epithelial windows produced by a lipoidal degeneration of the pigment epithelial cells. The experiment provided a fortuitous model for direct correlation of clinical and histologic observations of myriad uniform, tiny, depigmented, hyperfluorescent, nonleaking spots at the level of the retinal pigment epithelium.

Effects of repeated microwave irradiations to the albino rabbit eye.

Albino rabbits were exposed to repeated microwave irradiations once daily for a month. Clinical examination was carried out for a period up to one year. No changes occurred below 300 mW./cm.2. At and above this level posterior subcapsular iridescence and posterior cortical cataracts were produced. The histologic findings in posterior subcapsular iridescence are presented. It appears that the nonprogressive posterior cortical cataracts are a result of the temperature levels generated by the microwaves in the immediate retrolental area.

Dexamethasone protection against photochemical retinal injury.

Photochemical retinal injury was produced in the foveomacula of the rhesus monkey using the light from an indirect ophthalmoscope. The eyes were examined by both light and electron microscopy. Damage consisted of vacuolization of the retinal pigment epithelium and neurosensory retinal layers. Pretreatment with subcutaneous injection of dexamethasone for 16 weeks prior to light exposure markedly decreased damage to the retinal pigment epithelium, but had no apparent effect on damage to the neurosensory retina in eyes examined 18 hours after exposure. The mechanism responsible for this protective effect is unknown.

Congenital hereditary stromal dystrophy of the cornea.

Cornea from patients in two separate pedigrees showing dominant inheritance of a congenital nonprogressvie corneal clouding were examined by light and electron microscopy. The characteristic changes of abnormal corneal lamellae were widely and rather uniformly distributed throughout the stroma. The remaining corneal layers were normal. The findings are consistent with a diagnosis of congenital hereditary stromal dystrophy of the cornea, which differs greatly on both histologic and clinical grounds from the entity known as congenital hereditary endothelial dystrophy of the cornea.

The basement membrane exfoliation syndrome.

Previous observations suggest that "pseudoexfoliation of the lens capsule" may be a disease in which cells produce abnormal basement membrane material. Electron microscopic studies indicate that exfoliative material can be produced by cells throughout the anterior segment of the eye. This report describes abundant exfoliative material on the ciliary and iridic epithelia but not on the surface of the lens whose epithelial cells were completely necrotic. Exfoliative material also was observed in the anterior iridic stroma close to a newly formed abnormal endothelial basement membrane, suggesting that exfoliative material may be produced locally within the iris. Furthermore, typical exfoliative material, best considered a filamentous, banded basement membrane with 500-A periodicity, in the wall of a short posterior ciliary artery in the orbit indicates that the exfoliative process is not solely limited to ocular tissues. The term "basement membrane exfoliation syndrome" is proposed for this entity.

Lattice corneal dystrophy. Report of an unusual case.

The clinical, histochemical, light and electron microscopic evaluation of a case of lattice corneal dystrophy, appears clinically as an atypical granular dystrophy. There is structural and histochemical differentiation of the two dystrophies. Electron microscopy is often an invaluable aid in establishing a definitive diagnosis. The possible sources of the filamentous material found in lattice corneal dystrophy are discussed. It seems that not only keratocytes, but also corneal epithelial cells, occasionally may have the ability to elaborate the abnormal material that is considered to be amyloid in nature.

Patterned dystrophies of the retinal pigment epithelium.

Three varieties of patterned dystrophies of the retinal pigment epithelium have been described in the literature: They are reticular dystrophy, macroreticular dystrophy, and butterfly-shaped pigment dystrophy of the fovea (macula). They are all inherited and are bilateral and symmetric. Results of retinal-function tests in all three varieties were essentially normal, except for the electro-oculogram in the butterfly-shaped pigment dystrophy. We have observed within a single family one member manifesting butterfly-shaped pigment dystrophy, one member with macroreticular dystrophy, and one member with probable reticular dystrophy. Electrophysiologic studies of the retina in these patients were in accord with those already reported, except for supernormal scotopic responses in the latter two patients. This family demonstrates the linkage necessary to tie together a number of entities heretofore considered as separate.

Congenital glaucoma associated with a chromosomal defect. A histologic study.

A pair of eyes with congenital glaucoma, one treated by goniotomy, was examined by light and electron microscopy. Examination of the drainage angles afforded the opportunity to compare anatomic changes in the treated eye with the surgically unaltered tissue of the fellow eye. The congenital glaucoma appeared to arise from compression of the trabecular meshwork and closure of the intertrabecular and transtrabecular spaces by a discontinuous "membrane" consisting of ectopic trabecular pillars that bridged the drainage angle from the iris root to the normally positioned uveal meshwork. Cleavage of trabecular pillars during goniotomy and conversion of angle architecture to that of a nonglaucomatous neonatal eye suggest that aberrant or ectopic trabecular pillars acted mechanically in maintaining angle compression. The uveal and corneoscleral meshwork and Schlemm's canal are present and appear normal.

Diffuse iris nevus manifested by unilateral open angle glaucoma.

Uncontrolled unilateral glaucoma developed in the right eye of a 24-year-old woman. It was caused by the diffuse growth of a nonpigmented nevus of the iris into the anterior chamber angle. Histologically, the nonpigmented nevus cells in the angle were distinguishable from a proliferation of corneal endothelium. Clinically, there was no heterochromia, and a tumor was not suspected as the cause of the glaucoma.

Proliferative endotheliopathy with iris abnormalities. The iridocorneal endothelial syndrome.

Sixteen cases of essential iris atrophy and two of iris nevus (Cogan-Reese) syndrome were reviewed retrospectively by light and electron microscopy. Varying degrees of corneal endothelial proliferation onto the trabecular meshwork and anterior iris were seen in all cases. The demonstration of an endothelial-abnormal basement membrane complex on the anterior iridic surface, deep to synechias in over half the cases, indicates that endothelialization may be primary, since it precedes the formation of anterior synechias. Pathologic and clinical evidence suggests that the iris nevus syndrome, Chandler's syndrome, and essential iris atrophy represent a continuum of clinical manifestations of a single disease process involving proliferation of the corneal endothelial and characteristic iris abnormalities; the latter may be secondary to variations in the pattern, rate, and extent of endothelial proliferation. We suggest the term "proliferative endotheliopathy" to emphasize the common pathogenetic role of corneal endothelial proliferation in all three entities (iris nevus syndrome, Chandler's syndrome, and essential iris atrophy). A more succinct alternate term is "the iridocorneal endothelial (ICE) syndrome."

Corneal immunoglobulin deposition in the posterior stroma. A case report including immunohistochemical and ultrastructural observations.

Corneal buttons from a patient with bilateral, central, deeply located white corneal deposits that resembled the clinical description of filiform dystrophy were examined by means of light microscopy, immunohistochemistry, and electron microscopy. With light microscopy, the acidophilic fusiform deposits were seen to be oriented parallel to the stromal lamellae and were mostly in the pre-Descemet region. Immunohistochemical studies disclosed that the stromal lesions stained positively for IgG and lambda light chain. With electron microscopy, the immunoglobulin deposits within the deep corneal stroma appeared to be locally synthesized by the keratocytes. Recent examination of the patient's serum failed to disclose dysproteinemia.

Pathology of human cystoid macular edema.

The light and electron microscopic findings are reviewed in two patients who had eyes enucleated for peripheral choroidal malignant melanomas. Preoperatively, cystoid macular edema was documented by fluorescein angiography in the melanoma-containing eye in both patients. Intracytoplasmic swelling (edema) of the Müller (glial) cells is the anatomical basis for the macular edema. Intercellular (extracellular) collections of fluid probably are late, endstage results of the process that result form prolonged, excessive, intracellular edema, cell death and disruption. The process probably rests on an ischemic basis, as evidenced by severe changes in the microvasculature. In the one patient in whom the optic nerve was available for study, marked intracellular swelling (edema) of glial cells in the lamina choroidalis of the optic nerve head was present, associated with compression of the adjacent axons. The nearby temporal, parapapillary retina also showed edema of Müller cells, and compression of the nerve fibers (ganglion cell axons), suggesting a more widespread process than was clinically evident. Again, severe changes were present in the microvasculature, both in the optic nerve and parapapillary retina. The underlying cause of the microvasculature changes that lead to ischemia, perhaps an intrinsic pharmacologic agent, is yet to be found.

Lipoidal degeneration of the retinal pigment epithelium.

Vacuolation of the retinal pigment epithelium in the foveomacular region of aging rhesus monkey eyes was re-examined with the eyes initially fixed in osmium tetroxide to retain the alcohol-soluble lipid. All vacuoles were found to be completely occupied by lipid material. Similar cells were positive to oil red O. The vacuolation of the pigment epithelial cell is considered to be a form of lipoidal degeneration.

A histologic study of calcific and noncalcific band keratopathies.

One hundred five cases previously diagnosed as band keratopathy were reexamined. We found that band keratopathy was calcific noncalcific, or mixture of both. The noncalcific band was identified as elastotic degeneration of collagen, known clinically by various alternate terms. Cases of so-called reduplication of Bowman's membrane were reexamined, and many demonstrated production of a thick basement membrane of the corneal epithelium, with or without massive calcification. Identification of calcific-band keratopathy was made by transmission electron microscopy even when the tissue had been previously decalcified.

Electron microscopic study of human papilledema.

Papilledema associated with neoplastic invasion of the orbit in the optic disks of two patients was found and examined by light and electron microscopy. Pathologic changes in the optic nerve head and nerve included axonal degeneration and mild interstitial edema. Axonal swelling appeared to be the major factor in the overall increase in tissue volume of the optic nerve head. Vascular and perivascular glial alterations were nonspecific.

A histologic study of regional choroidal dystrophy.

Light and electron microscopy studies of eyes removed from an 84-year-old man after death indicated a normal optic nerve despite severe peripapillary choroidal atrophy. In the area of atrophy, the choriocapillaris, retinal pigment epithelium, and photoreceptors were absent and there was a marked decrease in choroidal arteries and veins. Bruch's membrane was intact except for several breaks in the peripapillary region. Müller cells, in the region of atrophy, produced an aberrant, thick basement membrane either in the outer layers of the neurosensory retina or directly applied to Bruch's membrane. On the basis of this study, we postulate that the primary abnormality in this disease is of the choroidal vasculature.

Macular edema and cystoid macular edema.

We examined the foveomacular regions from three eyes in which fluorescein angiography had demonstrated the characteristic appearance of cystoid macular edema by light and electron microscopy. Cystoid macular edema was present in two eyes (one of which was from a 63-year-old diabetic man) that contained peripheral choroidal melanomas, and in a third eye from a patient with diabetes only. By light microscopy, cystoid macular degeneration was obvious only in the third eye. The electron microscopic findings common to all three eyes were widespread swelling and necrosis of Müller cell cytoplasm. There was no enlargement of intercellular spaces. There was secondary neuronal degeneration. Retinal vascular changes, consisting mainly of endothelial cell abnormalities, were found in all cases but were far more common in the two eyes from diabetic patients. The retinal vascular changes were probably the cause of the cystoid macular edema.

Unusual superficial variant of granular dystrophy of the cornea.

Two patients with a superficial variant of granular dystrophy of the cornea occurring primarily in nongrafted eyes developed rapid progression of clinical manifestations and visual deterioration at an early age. No other members of their family were known to be affected. A clinical diagnosis of superficial corneal dystrophy, type undetermined, was made. The histopathologic features of the corneas resembled the findings seen in Reis-Bücklers dystrophy and led to some confusion in the differential diagnosis. Electron microscopic studies in both cases unequivocally established the diagnosis of granular dystrophy.