Three autosomal dominant corneal dystrophies map to chromosome 5q.

The two most common autosomal dominant dystrophies of the corneal stroma are lattice corneal dystrophy type I and granular dystrophy. A third autosomal dominant stromal dystrophy (Avellino) has also been recognized. Chromosome linkage analysis of four families with Avellino dystrophy mapped the disease-causing gene to chromosome 5q. Subsequent linkage analysis of two families with typical lattice dystrophy and two with typical granular dystrophy also revealed significant linkage with the same markers. Thus, each of three clinically and histopathologically distinct phenotypes is independently linked to 5q. The maximum combined lod score using all 114 affected patients was 28.6 with marker D5S393. None of the 14 known human amyloid-associated genes map to chromosome 5.

No effect of concanavalin A on the corneal graft reaction.

Penetrating corneal homografts were performed in albino rabbits. The experimental group received grafts soaked in a solution of concanavalin A; the control group received grafts soaked in lactated Ringer's solution. Animals with technically successful grafts were subsequently exposed to an additional antigenic stimulus from the corneal donor via skin grafting. This procedure produces a uniformly high rate of corneal graft rejection. The two groups were compared for the frequency and onset of the graft reaction. Results demonstrated no difference between control and experimental groups. The significance of these findings is discussed.

Altered antigenicity of keratan sulfate proteoglycan in selected corneal diseases.

Monoclonal antibody against keratan sulfate (KS) was used for immunofluorescent staining of sections of human corneas from 8 normal eyes, 19 with keratoconus, 4 with pellucid marginal degeneration, 5 with primary macular corneal dystrophy, and 1 with recurrent macular corneal dystrophy. The anti-KS monoclonal antibody did not stain the corneas with primary macular corneal dystrophy, but stained all other corneas to varying degrees. Staining intensity was weaker than normal in most keratoconus and pellucid marginal degeneration corneas, and was very weak in a case of macular corneal dystrophy that had recurred in a transplanted normal cornea. In several corneas with keratoconus, normal staining was seen at the periphery, and staining intensity decreased in the thinned central portion of the stroma. The decreased KS staining was not localized in stromal scar tissue found in the keratoconus and pellucid marginal degeneration corneas. Quantitation of relative staining intensity found keratoconus and pellucid marginal degeneration corneas to be 49% and 40% as intensely stained, respectively, as normal corneas, a statistically significant decrease (P less than 0.01). Distribution of staining intensities of the keratoconus corneas demonstrated a single modality. These results are in agreement with findings of previous biochemical studies, which show reduction of highly sulfated keratan sulfate epitopes in corneas from keratoconus and pellucid marginal degeneration, and absence of sulfated keratan sulfate epitopes in macular corneal dystrophy.

Detection of specific collagen types in normal and keratoconus corneas.

Keratoconus is a corneal disease of unknown cause that involves a progressive thinning and scarring of the corneal connective tissue. We examined normal human and keratoconus corneas, including one healed penetrating keratoplasty specimen. Organ cell cultures of normal and keratoconus corneal specimens were labeled with radioactive proline and analyzed by CM-cellulose chromatography and slab gel electrophoresis to determine collagen biosynthesis. Collagen types I and III were synthesized in similar amounts by normal and keratoconus stromacytes in culture. Specifically purified antibodies were used to determine the distribution of collagen types in tissue sections by immunofluorescence. The distribution of collagen types I, III, and IV in keratoconus was also similar to that in normal corneas, except that scarred regions in keratoconus and at the host-graft juncture were largely type III. Immunofluorescent reaction of the anti-type IV collagen antibodies with Bowman's layer, in particular, and Descemet's membrane in keratoconus specimens indicated extensive destruction. Basement membrane destruction may play an important role in this disease.

Pellucid marginal corneal degeneration.

Pellucid marginal degeneration of the cornea is a bilateral, clear, inferior, peripheral corneal-thinning disorder. Protrusion of the cornea occurs above a band of thinning, which is located 1 to 2 mm from the limbus and measures 1 to 2 mm in width. American ophthalmologists are generally not familiar with the condition because most of the literature concerning pellucid degeneration is European. Four cases are described. This condition is differentiated from other noninflammatory cornel-thinning disorders such as keratoconus, keratoglobus, keratotorus, and posterior keratoconus. It is also differentiated from peripheral corneal disorders associated with inflammation such as Terrien's peripheral corneal degeneration, Mooren's ulcers, and ulcers from connective tissue disease.

Posterior keratoconus.

Posterior keratoconus is a rare corneal disorder characterized by a total or localized noninflammatory thinning of the cornea. In front of a conical protrusion of the posterior corneal curvature, there is a thinned stroma and nonprotruding anterior surface. A corneal button from a patient with bilateral posterior keratoconus was studied by light and electron microscopy. Descemet's membrane, particularly in the area of stromal thinning, demonstrated abnormal anterior banding, a multilaminar configuration, and localized posterior excrescences. These alterations suggest an early pathogenetic mechanism, which probably originated prior to the fifth or sixth month of gestation.

Surgical correction of high postkeratoplasty astigmatism. Relaxing incisions vs wedge resection.

Improved techniques and procedures have resulted in a higher rate of clear grafts after penetrating keratoplasty. A clear graft, however, does not give a good visual result if high corneal astigmatism prevents the successful wearing of spectacles or contact lenses. This article describes the methods and results of two microsurgical techniques--the corneal wedge resection to steepen the flat meridian and relaxing incisions to flatten the steep meridian. Average reduction in corneal astigmatism was greater for the wedge resection (ten cases) (6.50 diopters as compared with 4.25 D [16 cases] for the relaxing incisions). The relaxing incisions operation was successful in 75% of cases with stabilization of corneal curvature readings in an average of three weeks and is an outpatient procedure. After a wedge resection, corneal stabilization usually takes months. We believe that wedge resection should be reserved for cases in which relaxing incisions are unsuccessful.

Bacterial corneal ulcers in cosmetic soft contact lens wearers.

Soft contact lenses provide a safe alternative to spectacles for more than 1 million patients. However, the hazard of bacterial corneal ulcers exists. This report describes five cosmetic soft contact lens wearers who developed bacterial corneal ulcers. In three cases, the resulting visual acuity was 6/120 or less. Possible sources of contamination are discussed, but in no case was it determined.

Subepithelial infiltrates: a probable sign of corneal transplant rejection.

A previously undescribed slit-lamp manifestation of a probable corneal transplant rejection reaction was found in 22 patients among 145 who underwent penetrating keratoplasty during a two-year period. The reaction consisted of subepithelial infiltrates that were located only in the donor tissue; were without associated conjunctivitis; and that occurred six weeks to 21 months postoperatively, either alone or in association with epithelial and/or endothelial rejection; and that responded well to topical corticosteroid treatment. In one case, the subepithelial infiltrates preceded a severe endothelial rejection by only a few days. The lesions are a warning that all is not well and that corticosteroid therapy should be instituted or increased.

Evaluation of soft contact lens disinfection in the home environment.

Recent reports of bacterial corneal ulcers in cosmetic soft contact lens wearers prompted an evaluation of one possible source of contamination, inadequate home disinfection of the lenses. Twenty-nine patients were asked to come for an early morning examination. They were told not to wear their lenses so their usual home disinfection procedure could be observed. On arrival, extensive bacterial and fungal cultures were taken of the solution in the previously unopened cases. Ten of the 29 patients (34.5%) had contaminated cases. Some patients did not follow the manufacturer's disinfection guidelines. The current disinfection procedure has repeatedly proven adequate in the laboratory. However, the practical fact is that a substantial percentage (34.5% in this study) of soft lens wearers are inadequately disinfecting their lenses. This serves as a possible source of contamination leading to bacterial corneal ulcers.

Familial corneal hypesthesia.

A 4-year-old boy with severe, diffuse, asymptomatic, punctate, epithelial corneal erosions had bilateral sharply decreased corneal sensation with normal skin sensation in the distribution of the trigeminal nerves. Subsequent family studies disclosed five family members with similar corneal changes and decreased corneal sensation and no punctate erosions. None had decreased skin sensation in the distribution of the fifth cranial nerve. No environmental factors or evidence of local or systemic disease accounted for these findings.

Diagnosis of early lattice corneal dystrophy.

Seven children from two unrelated families had lattice corneal dystrophy. Their ages ranged from 3 to 13 years at initial examination. The children were observed for an average of 35 months. Three distinct early slitlamp characteristics were found. The first characteristic was subepithelial white opacities that were discrete, round or ovoid, nonrefractile, nonstaining, variably sized (estimated at 0.1 to 0.5 mm), and larger than the previously reported minute refractile dots. The second finding was a diffuse axial anterior stromal haze that was either the initial sign or developed in conjunction with the other two characteristics. The third finding was anterior stromal dots and filamentary lines that were refractile on indirect slitlamp illumination and white on direct illumination. Knowledge of these three slitlamp characteristics in conjunction with examination of older family members wil facilitate the early diagnosis of lattice corneal dystrophy.

Clinical types of corneal transplant rejection. Their manifestations, frequency, preoperative correlates, and treatment.

We report a retrospective series of 156 penetrating keratoplasties that were performed in 144 patients during a two-year period, with a minimum of one-year follow-up. Three different types of rejection were identified--endothelial rejection, epithelial rejection, and subepithelial infiltrates (SEIs). We also report the clinical signs, frequency, preoperative correlates, significance, and treatment of each type of rejection. The overall frequency of any kind of rejection was 29%. Endothelial rejection was seen in 21% of the grafts, epithelial rejection was seen in 10% of the grafts, and SEIs was seen in 15% of the grafts. The frequency of endothelial rejection increased with preoperative corneal vascularization. All three types of rejection decreased in frequency with the increasing age of the recipient. Endothelial rejection was more successfully treated in the cases that had no preoperative stromal vascularization.

Photocoagulation. Its effect on the corneal endothelial cell density of diabetics.

The endothelium of 40 eyes from 38 diabetics were examined before and after argon photocoagulation. Twenty-two eyes were reexamined six weeks postoperatively. Changes in endothelial cell density were compared with regard to the energy delivered to the eye. There was no statistically significant change in the endothelial cell density in the immediate postoperative period. A statistically significant but small change in endothelial cell density was found in the six-week follow-up group when cell density was compared with energy delivered to the eye by the argon laser photocoagulator. Implications and possible causes for these observations are discussed.

Ocular Ehlers-Danlos syndrome with normal lysyl hydroxylase activity.

We report two brothers affected with what has been called either fragilitas oculi or the Ehlers-Danlos syndrome type VI. Previously reported cases of the Ehlers-Danlos syndrome type VI showed a deficiency of lysyl hydroxylase in cultured fibroblasts. Assays of cultured skin fibroblasts from these two boys yielded normal activity of this enzyme, suggesting that there are two variants of this disease.

Cornea pseudoguttata: a clinical and histopathologic description of endothelial cell edema.

Cornea guttata is a well-recognized corneal condition that is characterized by localized thickenings of Descemet's membrane. When these lesions disrupt, the regular endothelial mosaic, dark spots are seen in specular reflection. This same clinical appearance can be present during short-term episodes of iritis and corneal inflammation. Since it disappears with resolution of the inflammation, true cornea guttata (thickening of Descemet's membrane) obviously does not occur. Three cases of this transient clinical entity occurred. Production of iritis and corneal inflammation in rabbits with the use of bovine serum albumin and cautery resulted in the same transient appearance of dark spots, which interrupted the normal endothelial mosaic seen in specular reflection. Scanning and transmission electron microscopy of the cornea "pseudoguttata" disclosed transient endothelial cel edema.

Traumatic corneal endothelial rings.

Nonpenetrating "blast injuries" to the eye in two patients resulted in multiple, small, corneal epithelial foreign bodies that were associated with characteristic ring-shaped opacities of the corneal endothelium. These endothelial lesions were clinically visible immediately after injury and became more pronounced during the next several hours. They disappeared within days and resulted in no permanent loss of visual acuity. This communication describes and illustrates the appearance of these endothelial lesions both clinically and in an animal model. Light and electron microscopic observations of an experimental model, with the use of monkey and rabbit eyes, revealed that the ring-shaped opacities resulted from swelling of the corneal endothelium, as well as accumulation of fibrin and leukocytes on the injured cells. Except for the epithelial impact site and the concussion injury of the endothelium, the cornea was uninvolved, and the stroma remained clear.

Posterior corneal vesicles.

Two male and four female patients had posterior corneal vesicles and scalloped lesions. Ages ranged from 7 to 24 years. Uncorrected visual acuities were 6/6 or better OU. All cases were unilateral. There was no other ocular abnormality. The lesions were at the level of Descemet's membrane and endothelium. Results of specular microscopic examination suggested that the scalloped lesions could be the result of coalescence of vesicular defects. Several vesicles were surrounded by grayfish halos. The remainder of the cornea was normal. Thirty family members were found to be unaffected. These lesions must be differentiated from those in posterior polymorphous dystrophy congenital glaucoma, and forceps injury. Previous reports have implied a herpetic origin; although their etiologic character is not known, the present study does not support this conclusion.

Development of keratoconus after contact lens wear. Patient characteristics.

A retrospective review of 398 eyes of 199 patients with keratoconus revealed 106 eyes of 53 patients with an association between contact lens wear and the development of keratoconus. The absence of keratoconus at the time of contact lens fitting was confirmed by slit-lamp examination, keratometry readings, and manifest refraction. Keratoconus was diagnosed after a mean of 12.2 years of contact lens wear. This group was compared with patients with sporadic keratoconus with either no history of contact lens wear or a history of contact lens wear after the diagnosis. They were older at the time of diagnosis, had central vs decentered cones, and had a tendency toward flatter corneal curvatures. We believe that these patients suggest that long-term contact lens wear is a factor that can lead to keratoconus.

Fleck corneal dystrophy.

Fourteen members of four families with fleck systrophy of the corneal stroma were examined and studied. Corneal and lens changes were noted in all patients. Corneal sensation was normal. Corneal biopsies were performed on two patients and a corneal button of a patient with fleck dystrophy and keratoconus was studied. Light and electron microscopy and histochemical studies showed this dystrophy to consist of abnormal keratocytes with variable numbers of membrane-limited intracytoplasmic vacuoles containing a granular to fibrogranular material that stains positively for mucopolysaccharide. This appears to be the first reported incidence of a dominantly inherited disorder of mucopolysaccharides affecting the eyes.