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Human transforming growth factor β induced protein (TGFBIp) is composed of 683 residues, including an N-terminal cysteine-rich (EMI) domain, four homologous fasciclin domains, and an Arg-Gly-Asp (RGD) motif near the C-terminus. The protein is of interest because mutations in the TGFBI gene encoding TGFBIp lead to corneal dystrophy (CD), a condition where protein aggregates within the cornea compromise transparency. The complete three-dimensional structure of TGFBIp is not yet available, with the exception of a partial X-ray structure of the archetype FAS1 domain derived from Drosophila fasciclin-1. In this study, small-angle X-ray scattering (SAXS) models of intact wild-type (WT) human TGFBIp and a mutant (R124H) are presented. The mutation R124H leads to a variant of granular CD. The deduced structure of the TGFBIp monomer consists of four FAS1 domains in a simple "beads-on-a-string" arrangement, constructed by the superimposition of four consecutive Drosophila fasciclin domains. The SAXS-based model of the TGFBIp R124H mutant displayed no structural differences from WT. Both WT TGFBIp and the R124H mutant formed trimers at higher protein concentrations. The similar association properties and three-dimensional shape of the two proteins suggest that the mutation does not induce any major structural rearrangements, but points towards the role of other corneal-specific factors in the formation of corneal R124H deposits., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We isolated and identified the major protein present in corneas with granular dystrophy (GCD). We compared Coomassie-blue-stained protein bands obtained on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) from the extracts of corneas with GCD, corneas with other disorders, and normal human corneal tissue. After SDS-PAGE and transfer to a polyvinylidene difluoride membrane, bands of interest were analyzed by amino acid sequencing and by Western blotting. Corneas with GCD were also examined immunohistochemically. On SDS-PAGE a 63-kd band just below albumin was present in extracts of all corneas. The albumin/63-kd ratio was normally approximately 3:1, suggesting that the protein is a dominant constituent of the cornea. This band was much more plentiful than normal in corneas with GCD. Amino-terminal sequence analysis of the protein revealed a Gly-Pro-Ala-Lys-Ser-Pro-Tyr-Gln-Leu-Val-Leu-Gln-His-Ser-Arg sequence indistinguishable from an amino-terminal protein sequence deduced from a cDNA clone designated beta ig-h3, and it as well as the abnormal accumulations in GCD cross-reacted with beta ig-h3 antiserum. The presence of excessive beta ig-h3 in human corneas with GCD together with reported mutations in the beta ig-h3 gene in GCD suggests that the mutated gene product is a fundamental constituent of the characteristic corneal accumulations in GCD.

Background: The frequency of different types of macular corneal dystrophy (MCD) was determined in Iceland where MCD accounts for one third of every penetrating keratoplasty., Methods: The authors determined the serum levels of antigenic keratan sulfate (aKS) in 27 patients with MCD and 53 unaffected family members by an enzyme-linked immunosorbent assay that uses an anti-KS monoclonal antibody (5-D-4). The authors also stained sections from 37 corneal buttons (including 2 regrafts) from 23 patients with MCD by the avidin-biotin complex method using the same anti-KS monoclonal antibody., Results: Based on the serum analyses, 22 patients had MCD type I and 5 had MCD type II. The corneas from patients without detectable KS in the serum lacked immunohistochemical reactivity to the anti-KS antibody. Every MCD cornea examined from individuals with normal serum KS levels showed KS reactivity. All 53 unaffected siblings and parents carrying the recessive gene had normal serum KS levels., Conclusions: Macular corneal dystrophy types I (78.6%) and II (21.4%) both occur in Iceland. Members of affected sibships had only one of these types, not both. Nine patients with MCD type I and four persons with MCD type II belonged to a large pedigree in which individuals have been traced as far back as the beginning of the 16th century. The linking of patients with MCD types I and II in an inbred pedigree suggests that both types may be manifestations of the same abnormal gene rather than independent entities. The serum KS levels were not helpful in detecting heterozygous MCD carriers.

Background and Methods: The authors report the clinical and ocular histopathologic findings in three patients with longstanding unilateral post-traumatic blindness. After one or more decades, acute pain associated with conjunctival hyperemia and apparent keratoprecipitates or a hypopyon developed in the affected eye of each individual. Phacoanaphylaxis was diagnosed preoperatively in two patients., Results: Calcified granular lens fragments were dispersed throughout all three eyes. The anterior chamber in all patients contained extracellular calcified lens particles, but only one eye contained conspicuous macrophages. Two eyes showed elevated intraocular pressure (IOP), and in one patient calcified particles extended into a glaucomatous optic nerve head., Conclusion: To the authors' knowledge, this is the first report describing a rare condition involving the intraocular dispersal of calcified lens particles after disruption of the lens capsule. The authors have designated this entity as calcific phacolysis.

The expression of the human T-cell lymphotropic virus type 1 (HTLV-1) tax gene in transgenic mice has been shown to result in the development of neurofibromas. Further characterization of these transgenic mice has revealed other significant pathologic similarities between this transgenic mouse model and human neurofibromatosis (NF). Pheochromocytomas of the adrenal medulla and hamartomas of the iris are well-recognized manifestations of human NF. Adrenal medullary tumors have been found in 68% of transgenic animals that were studied. They appear, however, not to be pheochromocytomas, but rather composed of undifferentiated spindle cells. Proliferation of fibroblastlike cells in the iris also occurs in one-half of the transgenic animals surviving more than 6 months. Melanocytes, however, have not been found in the transgenic iris lesion, although they are characteristically found in the Lisch nodules of human NF. The similarities between human neurofibromatosis and this transgenic mouse model (in which the overexpression of a single gene results in neoplasia) are discussed. This transgenic system may provide further insights into molecular mechanisms involved in the pathogenesis of neurofibromatosis.

Retinoic acid receptors (RARs) modulate gene expression following association with retinoic acid (RA). In transient transfection, an RAR alpha-beta-galactosidase fusion protein (RAR-LacZ) was able to transactivate expression in the absence of RA. When expressed in the ocular lens of transgenic mice, this constitutively active RAR-LacZ fusion gene resulted in founder and progeny animals that exhibited cataracts and microphthalmia, both being characteristics of retinoid-induced teratogenesis. The transgenic phenotypes indicate that retinoid teratogenesis can be mimicked by expression of a constitutively active RAR-LacZ fusion protein in retinoid-sensitive tissues.

The role of the lens in early eye development was examined in transgenic mice carrying the cytotoxic diphtheria toxin A gene driven by hamster alpha A-crystallin promoter sequences. Mice hemizygous for this construct are microphthalmic and contain a vacuolated and highly disorganized lens, whereas adult homozygous mice are completely ablated of the lens and lack a pupil, aqueous and posterior chamber, vitreous humor, iris, and ciliary body and show extensive convolution of the sensory retina. Developmental analysis of animals homozygous for the transgene revealed that the optic cup and lens vesicle form normally and that ablation of the lens occurs as a gradual degenerative process beginning between Days 12 and 13 of gestation. Degeneration of the lens vesicle coincides with retarded growth and development of the neuroretina, sclera, and cornea. The anterior lip of the optic cup fails to differentiate into the normal epithelium of the iris and ciliary body and the vitreous body does not develop. Although the retinal layers apparently form normally, retinal folding becomes prominent following lens degeneration. These results suggest that development of a functional lens from Embryonic Day 12.5 onward is critical for formation of the ciliary epithelium, iris, and vitreous body, as well as for appropriate growth, development, and maintenance of morphology of the retina, cornea, sclera, and optic nerve. Our results also provide information on the time course of DT-A-mediated cell destruction in vivo and are discussed in context with previous lens ablation studies and the importance of developmental analysis for interpretation of the extent to which morphogenetic aberrations are concurrent with or secondary to genetic ablation of the target tissue.

Two cases of malignant syringoma of the eyelid are reported. The first patient, a 20-year-old woman, presented with a one year history of a slowly growing nodule in the left lower eyelid. The lesion recurred five months after excision, slowly grew over the ensuing two and one-half years, and was reexcised. The second case was an 18-year-old man who was first examined by an ophthalmologist because of a slowly enlarging, painless induration of his right lower eyelid for two years. Histologic examination of the excised lesions from both patients disclosed proliferated ducts lined by two layers of epithelium infiltrating the dermis and subcutaneous tissue; there was skeletal muscle and perineural invasion, but only minimal cellular atypia. Malignant syringomas are rare forms of sweat gland carcinoma, which most often occur on the upper lip and to our knowledge have not been reported on the eyelid. These tumors probably arise from eccrine ducts, are more common in women, and have a peak incidence in the fifth decade. The histologic feature that best indicates prognosis is the degree of cellular atypia. Patients with cytologically well-differentiated tumors do well following complete local excision. Features that help to distinguish malignant syringoma from its benign counterpart are the larger size, solitary nature, and subcutaneous, muscular, and perineural invasion.

Melanin pigmentation of the corneal epithelium was induced in pigmented guinea pigs by the topical application of colchicine to their eyes or by corneal cauterization with silver nitrate. With colchicine the pigmentation was preceded by the development of an abnormal corneal epithelium in which numerous cells became arrested in cell division. The corneal melanosis resulted largely from the migration of melanocytes into the corneal epithelium from the normally pigmented contiguous conjunctiva and to a lesser extent from the presence of melanin granules within corneal epithelial cells. In both models a leukocytic and vascular invasion of the cornea proceded and accompanied the migration of melanocytes into the corneal epithelium. Electron microscopy disclosed cells with the same morphology as conjunctival melanocytes between the epithelial cells of the cornea. Mature melanin granules were also present within some squamous epithelial cells as individual granules or as clusters. The ultrastructural findings are viewed in relation to how melanin granules are transferred from melanocytes to epithelial cells. Evidence is presented which suggests that malanin granule transfer may follow the fusion of the membranes of the melanocytes and epithelial cells.

The glycosaminoglycans synthesized by 5 corneal explants with macular corneal dystrophy were analyzed by sequential degradation using heparitinase (and/or butyl nitrite), chondroitin ABC lyase, chondroitin AC lyase, and keratan sulfate endo-beta-galactosidase. The tissue was first pulse-labeled by incubation in phosphate-buffered saline (pH 7.3) containing 100 muCi/ml 3H-glucosamine and approximately 1000 muCi/ml 35S-sulfate for 1 hour and chased with Eagle's minimum essential medium containing 10% fetal calf serum. Notable differences were detected between the products of these corneal explants with macular corneal dystrophy and controls that were prepared and analyzed in the same manner. As assayed by its susceptibility to keratan sulfate endo-beta-galactosidase degradation, corneal tissue with macular corneal dystrophy incorporated less 35S-sulfate, and usually less 3H-glucosamine, into keratan sulfate than normal corneas. The corneal explants with macular corneal dystrophy also synthesized prominent fractions which eluted from DEAE-Sephacel columns in 0.05 M tris(hydroxymethyl)aminomethane buffer (pH 7.2) with 0.15 M and/or 0.25 M lithium chloride after pronase digestion. Since normal corneas produced small quantities of material with a similar elution profile after preparation and analysis under identical conditions it is possible that the fractions are normal synthetic products of the cornea. The significance of these findings in the pathogenesis of macular corneal dystrophy remains to be determined.

A study of 11 consecutive patients with anterior uveal melanomas from one institution demonstrated the wide variation in the clinical and histopathologic manifestations of the tumors. The intraocular pressure in the involved eye compared with the fellow eye was elevated in five cases, equal in four, and reduced in two. Histologic studies suggest that the anterior uveal melanomas influence intraocular pressure through their effect on the balance between aqueous production and outflow. Three of the four patients with ciliary body melanomas and glaucoma died of metastatic disease within 3 years of enucleation.

A 63-year-old man, in good health previously, developed swelling and erythema of the right upper eyelid which progressed to involve both eyelids and surrounding tissues. After one month, he had a 9.0 x 9.0 x 3.5 cm mass despite two attempts at incisional drainage and treatment with antibiotics. Multiple asymptomatic erythematosus nodules (2-3 cm in diameter) developed on his back, trunk, and arms four weeks after onset of the eyelid erythema and swelling. Biopsies of two upper back papules and the eyelid disclosed cutaneous T-cell lymphoma, a lymphoproliferative malignancy of thymus derived lymphocytes originating in the skin. Systemic chemotherapy resulted in a marked decrease in the ocular adnexal mass but lymphomatous meningitis and quadriplegia developed. The patient died four months later; an autopsy was not performed. This case demonstrates that cutaneous T-cell lymphoma may rarely have its initial manifestation as a rapidly enlarging eyelid tumor.

The inherited disorder macular corneal dystrophy (MCD), a localized corneal mucopolysaccharidosis, is currently thought to result from an inability to catabolize corneal keratan sulfate (keratan sulfate 1). As studies on isolated cells have provided insight into metabolic abnormalities in other inherited disorders, we investigated cultured corneal fibroblasts from 4 patients with MCD from several standpoints. Lines of corneal fibroblasts with MCD could not be distinguished from controls with cytochemical methods known to stain the naturally occurring accumulations. In contrast to cultured fibroblasts from patients with mucopolysaccharidoses Type I-H (Hurler syndrome) and Type II (Hunter syndrome), corneal fibroblasts from patients with MCD did not accumulate abnormal quantities of (35)S-sulfate-labeled glycosaminoglycans, but like normal corneal and cutaneous fibroblasts reached a state of equilibrium within 2 days. Also, the rate at which sulfated glycosaminoglycans were removed from cultured corneal fibroblasts in MCD by secretion and degradation more closely resembled that of normal cells than those with the systemic mucopolysaccharidoses. The secretion of sulfated glycosaminoglycans into the nutrient medium by corneal fibroblasts from patients with MCD occurred at a linear rate comparable to that of other cells studied. The aforementioned data, nonetheless, remain consistent with the hypothesis that MCD is an inherited disorder of keratan sulfate I (corneal keratan sulfate) catabolism, as isolated corneal fibroblasts in contrast to corneal explants synthesize little or no keratan sulfate in culture. In view of the latter, we also compared the profile of (35)S-labeled glycosaminoglycans produced by a corneal explant from a patient with MCD with that normally synthesized by human corneal explants. The latter synthesized and secreted a population of (35)S-sulfate-labeled glycosaminoglycans with properties of keratan sulfate. Considerably less material with these attributes was identified with the same analytic techniques in the cornea with MCD or in its surrounding medium after the abnormal cornea had been incubated under identical conditions. In addition to manifesting an impaired synthesis of corneal keratan sulfate-like material, the cornea with MCD produced a greater percentage of chondroitin-6-sulfate than normal. These findings suggest that the synthesis of corneal keratan sulfate and other glycosaminoglycans may be altered in MCD.

Studies of corneal explants in the hamster cheek pouch chamber have demonstrated that blood vessels invade the cornea only if the tissue is first infiltrated by leukocytes. In view of this observation, a comparative study of the events that precede and accompany corneal vascularization was undertaken in various experimental models. A variety of established methods were used to induce corneal vascularization, including exposure of the cornea to noxious agents, intracorneal injection of antigens into sensitized animals, as well as maintaining animals on diets deficient in vitamin A or riboflavin. In all models studied, the corneal vascularization was a manifestation of the reparative phase of the inflammatory response. A conspicuous leukocytic infiltrate of the cornea preceded and accompanied the corneal vascularization in all of the models. Although the lesions varied in several respects in the different models, all models displayed three phases with regard to vascularization: an early prevascular phase of leukocytic infiltration, a second phase where blood vessels persisted in the cornea in the absence of leukocytes. The latent period that preceded vascularization was directly related to the time of the initial leukocytic infiltration. The models in which a delay occurred in the leukocytic invasion displayed a subsequent delay in the vascular ingrowth. Conversely, in experiments where there was a rapid and extensive leukocytic invasion, there was also an early and enhanced corneal vasoproliferative response. In the various modesl investigated, the sites of the leukocytic infiltration and subsequent vascular ingrowth into the cornea paralleled each other. The data further support the hypotheses that leukocytes are a prerequisite to corneal vascularization and that leukocytes produce one or more factors which stimulate directional vascular growth.

Investigations on several experimental models in the past have supported the hypotheses that corneal vascularization is a manifestation of the inflammatory response and that leukocytes perform an essential role in stimulating corneal vascular ingrowth. To evaluate the possible role of leukocytes further in this phenomenon, the effect of leukocyte elimination on corneal vascularization induced by silver nitrate cauterization was investigated. Weanling Fischer albino rats received doses of total body x-irradiation ranging from 1100 to 2100 rads to deplete circulating leukocytes, and corneal silver nitrate cauterization was performed 4 days later. In this model, animals that received 1500 rads or more total body x-irradiation became severely leukopenic within 4 days. As a rule, neither leukocytes nor blood vessels invaded the cauterized corneas, whereas both a leukocytic and vascular invasion occurred at lower doses of irradiation that did not totally eliminate circulating leukocytes. Corneal vascularization ensued if the corneal cauterization was performed immediately after total body x-irradiation with 1500 rads before the leukopenic effect of x-irradiation occurred. Control studies in which the cornea was cauterized 4 days after only the head received 1500 rads x-irradiation ruled out the possibility of irradiation-induced limbal endothelial damage as the explanation for the vascular suppression observed by x-ray treatment. In nonirradiated rats, silver nitrate cauterization of the cornea consistently induced corneal vascularization by 2 to 3 days. In further experiments, methylprednisolone acetate was administered subconjunctivally after corneal cauterization. This corticosteroid inhibited the infiltration of leukocytes and the subsequent vascular invasion into the corneal stroma, if administered immediately after silver nitrate cauterization. However, when the same glucocorticoid was administered 1 day after cauterization, both a leukocytic infiltration and vascular ingrowth occurred but to a less severe degree than in non-glucocorticoid-treated cauterized corneas. These investigations together demonstrated that a vascular ingrowth of the cornea did not follow corneal cauterization with silver nitrate in the absence of leukocytes, and gives further support to the hypothesis that leukocytes serve a crucial function in corneal vascularization.

Deoxycholate promotes phospholipase C degradation of endogenous phosphatidyl[3H]inositol (Pl), phosphatidyl[3H]inositol monophosphate (PIP) and phosphatidyl[3H]inositol bisphosphate (PIP2) in rat cornea and human platelets. Hydrolysis of phosphatidyl[3H]inositol significantly lags polyphospho[3H]inositide degradation. Concomitantly, formation of [3H]inositol monophosphate (IP1) lags behind [3H]inositol bisphosphate (IP2) and [3H]inositol trisphosphate (IP3) production. These results demonstrate that rat cornea and human platelet phospholipase C cause a preferential hydrolysis of the endogenous polyphosphoinositides rather than phosphatidylinositol.

During studies on the effect of murine cytomegalovirus on the developing retina, virus was inoculated into the eyes of newborn Swiss mice, and the animals were sacrificed at various times thereafter. Controls consisted of mice inoculated with ultraviolet-inactivated murine cytomegalovirus and uninjected mice. Marked lymphoid cell necrosis, thymic atrophy, pronounced growth retardation, bacteremia, and death occurred in the animals inoculated with live virus. this virus-induced injury resulted in a marked depletion of lymphocytes in the subcapsular and cortical areas of the thymus as well as in the spleen, lymph nodes, and Peyer's patches. Areas of necrosis with viral inclusions were present at the site of inoculation and in various other organs including the spleen and bone marrow. Since growth retardation has been associated with thymic atrophy due to other causes, the observed abnormal physical development in the present study was interpreted as a sequel to the thymic injury. An implication of this study is that some human infants with concomitant immune deficiency and viral infection may have a primary viral disease with resultant secondary lymphoid tissue alterations, rather than a thymic disorder with a subsequent viral infection.

A 23-year-old woman presented with a 19-year history of unilateral, intermittently painful, slowly progressive proptosis. Clinical examination disclosed decreased orbital resiliency and choroidal folds in the posterior pole. Orbital echography revealed an acoustically empty cystic lesion superotemporally. Computerized tomography demonstrated bony molding of the adjacent lateral orbital wall. At operation, a discrete, well-encapsulated mass was found adherent to the periorbita behind the lacrimal gland and extending into the muscle cone. There was no connection with the bony orbit. Histological examination disclosed the well-encapsulated cyst to be lined by pseudostratified ciliated columnar epithelium with goblet cells and filled with mucoid debris. We postulate that the cyst arose from respiratory epithelium sequestered during the intrauterine development of the paranasal sinuses.

Cytomegalovirus can produce a severe necrotizing chorioretinitis in patients on immunosuppressive therapy and infants born with congenital cytomegaloviral inclusion disease. To study the effect of cytomegalovirus on the eye, murine cytomegalovirus was injected into the eyes of nonimmunosuppressed Swiss CD-1 weanling mice. The eyes were then prepared for virus titer, as well as light and electron microscopy at variable periods after inoculation (1 to 28 days). From days 2 to 6, the hallmarks of cytomegalovirus infection, intranuclear and intracytoplasmic viral inclusions, were evident within cytomegalic cells. The major site of reaction was in the uveal tract, where necrosis and inflammation were prominent. Viral particles budding through the nuclear membranes into the perinuclear cisternae and vacuoles with viral particles could be seen in the cytoplasm of infected cells. In lesions older than 2 weeks, only a mild mixed inflammatory infiltrate and fibrosis were observed. Morphologic alterations unaccompanied by inflammation occurred in the outer sensory retina overlying infected retinal pigment epithelial cells. Multiple necrotic foci with inclusion-bearing cells in the liver indicated the systemic spread of virus from the eye. The titer of virus recovered from the eye peaked at day 4 and then declined to low levels, but infectious virus could still be isolated at day 28, even though viral particles were not seen morphologically at or after day 14. Many of the alterations seen in the model resemble those found in the human cytomegaloviral ophthalmitis.

In a clinical study of the essential iris atrophies, corneal edema occurred in 49 of 90 patients, and a characteristic hammered-silver appearance of the posterior cornea was visible in 54 cases. Intraocular pressure in the eyes with corneal edema ranged from normal to extreme elevation with glaucomatous damage, and lowering the pressure relieved the corneal edema in many cases with penetrating keratoplasty being effective when other measures failed. Electron microscopy of two keratoplasty specimens revealed extremely few, distinctly abnormal cells lining a collagenous layer posterior to Descemet's membrane.

The clinical presentation of an 11-year-old boy with unilateral posterior internal ophthalmomyiasis is described. Ophthalmoscopy of the affected eye in this individual disclosed characteristic subretinal depigmented linear tracks and a larva within the vitreous. The intravitreal larva was retrieved successfully by pars plana vitrectomy and identified as the first instar of Cuterebra sp. (rodent botfly) by scanning electron microscopy. This was done by examining the external features of the larva by scanning electron microscopy and comparing them to scanning electron micrographs that were prepared on other first instar larvae of flies known to be implicated in internal ophthalmomyiasis. The study demonstrates the usefulness of scanning electron microscopy for taxonomic identification of fly larvae. Since even a small fragment of these organisms may contain characteristic features of external morphology, scanning electron microscopy may be useful in cases where the specimen is damaged or incomplete.

Studies in the past have suggested that leukocytes are a prerequisite to corneal vascularization. To test this hypothesis further, experiments were conducted to determine whether the intracorneal instillation of polymorphonuclear leukocytes, lymphocytes, or components of leukocytes would induce a corneal vascular ingrowth. These cells or cellular fractions were injected intracorneally into Fisher albino rats whose circulating leukocytes had been depleted by total body x-irradiation. Polymorphonuclear leukocytes isolated from glycogen-induced peritoneal exudates caused a corneal vascular invasion, but lymphocytes obtained from thymus, spleen, and lymph nodes failed to do so. To learn whether an extractable factor could be isolated from polymorphonuclear leukocytes these cells were suspended in isotonic saline, ultrasonified and then centrifuged at 101,952g for 1 hour. Aliquots of the resulting sediment and supernatant were injected intracorneally into rats with radiation-induced leukopenia. The nonsedimentable supernatant caused corneal vascularization, but the sediment did not provoke the phenomenon. These studies not only provide further support for the hypothesis that leukocytes initiate corneal vascularization, possibly by the release of one or more heat labile chemical mediators, but directly implicate the polymorphonuclear leukocyte in this process.

The clinical and morphologic features of a pigmented squamous cell carcinoma of the bulbar conjunctiva in a 57-year-old black man are reported. The tumor resembled the more usual epibulbar squamous cell carcinoma but had many melanin containing cells within it. Transmission electron microscopy disclosed melanosomes within squamous epithelium, melanocytes, and macrophages. The only cells within the tumor with morphologic features of a malignant neoplasm were squamous in type. The literature on this rare conjunctival tumor, which has a good prognosis following complete excision, is reviewed. Pigmented squamous cell carcinomas need to be distinguished from the more common nodular melanomas, which have a more ominous outlook.

Morphologic observations on a peculiar type of corneal reaction with a predisposition for the superficial stroma of the interpalpebral portion of the cornea are reviewed. Histochemical evidence is provided which indicates that the corneal concretions, though not homogenous, are proteinaceous in nature and contain amino acids not normally detectable in the cornea. The corneal concretions were associated with conjunctival elastosis (pingueculae) in all 22 instances in which the eyes were sectioned in the horizontal plane. Identical concretions were identified within these associated pingueculae, as well as in a large percentage of other pingueculae and cutaneous lesions with actinic elastosis. The findings suggest that the abnormal material arises in the pericorneal conjunctival connective tissue from whence it diffuses into, and deposits in, the superficial corneal stroma. The data also raise the possibility that the concretions may be derived, at least in part, from altered elastic tissue. Morphologic and epidemiologic observations on the condition taken together strongly suggest that this unique reaction is a sequel to the cumulative effect of chronic actinic irradiation. Further observations on this keratopathy are needed to establish whether this unique response can be provoked by other noxious stimuli.

To gain insight into factors that might be responsible for the normal avascularity of the cornea and for its vascularization in certain pathologic states, an experimental model was designed in which corneal vascularization could be studied under controlled conditions in hamster cheek pouch chambers. Normal corneal tissue, as well as corneas that had been altered in a variety of ways (eg, boiled, autoclaved, freeze-thawed) were implanted into hamster cheek pouch chambers. The fate of the transplanted tissue was observed at regular intervals by direct visualization within the hamster cheek pouch at various magnifications and by light and electron microscopy. This report reviews observations on more than 300 such experiments. Normal and injured corneal autografts, allografts and xenografts and nonviable (autoclaved, boiled or freeze-thawed) corneas commonly became vascularized in the cheek pouch. When this occurred, a similar morphologic sequence of events preceded and accompanied the growth of blood vessels into the cornea. Vascular invasion was generally preceded by the formation of granulation tissue around the cornea. This was followed by a leukocytic, and frequently a fibroblastic, infiltration of the cornea. When cells did not invade the transplanted cornea, the cornea invariably remained avascular. In the present model, a swollen cornea was not a sufficient stimulus for corneal vascularization. The data suggest that under certain circumstances leukocytes may produce one or more factors which stimulate directional vascular growth. The findings are viewed in terms of current concepts on corneal vascularization.