Ben S. Fine

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.

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.

Diabetic choroidopathy. Light and electron microscopic observations of seven cases

The choroid of seven young patients (ages 20-29 years), who had had diabetes mellitus for many years (14-23 years) was studied by light and electron microscopy. The eight enucleated eyes were blind and painful as a complication of diabetes mellitus. Histopathologically, the choriocapillaris and other small choroidal blood vessels disclosed marked basement membrane thickening of their walls. Periodic acid-Schiff-positive homogeneous acellular nodules were present and resembled those of diabetic glomerulosclerosis (Kimmelsteil-Wilson disease). Some choroidal arteries were arteriosclerotic. Choroidal compromise was suggested by luminal narrowing of the capillaries, capillary dropout, and focal scarring. Choroidal neovascularization with subretinal fibrovascular membranes occurred in two patients at the midperiphery and periphery, and resembled those of retinitis proliferans. Leakage of proteinaceous fluid into the choroidal stroma and beneath the focally detached pigment epithelium was suggested by the electron microscopic observations. Choroidal vasculopathy in diabetes mellitus is similar to much of what has been described in other tissues of the eye and body, and suggests an important role in the pathogenesis of diabetic retinopathy since the outer retinal layers are largely dependent on the choroid for their nutrition and oxygenation.

Round and Oval Cones in Keratoconus

In advanced keratoconus, there are two cone types. The more common round or nipple shaped cone is limited in diameter but may reach any degree of conicity. The cone center lies mostly in the lower nasal quadrant. The oval or sagging cone, is often larger and lies more commonly in the inferotemporal quadrant close to the periphery. The oval cone is usually associated with more episodes of corneal hydrops, scarring and difficulty in fitting contact lenses. Histopathologic review of 23 cases (10 round, 13 oval), revealed that the oval group had more breaks in Bowmans membrane, 10.1 versus 5.0, (P smaller than 0.01), and a tendency toward greater pannus formation with more ruptures in Descemets membrane. We hope this clinicopathologic correlation may allow a more logical approach to patient care based on recognizing two different cone types in advanced keratoconus.

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.

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 clinicopathologic study of four cases of primary open-angle glaucoma compared to normal eyes.

Eight eyes obtained at autopsy from four patient who had chronic open-angle glaucoma were compared to eyes with normal aging changes. Three cases were characterized by early and pronounced abnormalities in the uveal portion of the drainage angle. The findings consisted of formation of an exaggerated scleral spur upon the scleral roll by accretion and compaction of the overlying uveal meshwork, hyalinization and atrophy of the adjacent ciliary muscle, and atrophy of the iris root. The fourth case showed widespread proliferation of endothelium into the lumen of Schlemms canal. We concluded that the predominant histologic findings in eyes with open-angle glaucoma consists of an exaggeration of normal aging processes, ranging in a spectrum from excessive involvement of the uveal pathway to excessive involvement of the canal of Schlemm pathway.

Observations on monkey eyes exposed to light from an operating microscope

Two cynomolgous monkeys were exposed to the light of an operating microscope. One eye was exposed to the light with the blue end of the spectrum filtered, while the other was exposed to unfiltered light. Neither group of eyes showed ophthalmoscopic evidence of a discrete retinal lesion. The eyes exposed to unfiltered light, however, showed histologic evidence of foveomacular change. The eyes exposed to filtered light showed lesser changes.

Spontaneous Degenerative Maculopathy in the Monkey

Maculopathy has many varied facets. The subhuman diurnal primate demonstrates some of the changes occasionally seen in clinical practice. Examination of 574 diurnal subhuman primates, mostly older rhesus monkeys, revealed the following: drusen-like bodies in the macula and frequently elsewhere in the eye grounds of 5.9%; crescent shaped lesions suggestive of choroidal rupture; and macular and perimacular lesions associated with myopia and complicated by choroidal neovascular ingrowth.

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 Bowmans 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.