Posterior Polymorphous Dystrophy Research Articles

Specular Microscopic Observation of Posterior Corneal Vesicles

Specular microscopic investigation was conducted on 5 cases with the diagnosis compatible with posterior corneal vesicles. Endothelial cells were considerably enlarged with a more or less indistinct margin. Deposits onto endothelial cells were occasionally seen. The results of specular microscopy suggest that posterior corneal vesicles be classified as a nonfamilial, unilateral variant of posterior polymorphous dystrophy of the cornea.

Differentiation of Posterior Polymorphous Dystrophy from Other Posterior Corneal Opacities by Specular Microscopy

Deep corneal opacities due to posterior polymorphous dystrophy, especially if they are mild, are frequently confused with changes due to other corneal conditions. In a series of 64 patients with deep corneal opacities (14 with Descemet's tears, 8 with posterior polymorphous dystrophy, 12 with interstitial keratitis, and 30 with keratoconus), specular microscopy enabled the differentiation of deep corneal changes provided some degree of corneal clarity was retained. The parallel “rail track” borders of old Descemet's tears were characteristic and differed from the “snail tracks” seen in posterior polymorphous dystrophy, which also showed characteristic rounded vesicular or doughnut-like lesions in Descemet's membrane. The appearances in interstitial keratitis were varied with poor detail in most cases because of corneal opacity. However, fine opacities consistent with ghost vessels were seen in interstitial keratitis and a resolving case showed fine, intersecting straight lines different from the bundles of parallel fine vertical lines of deep corneal striae in keratoconus. Specular microscopy also enables an assessment of the corneal endothelium which is important if intraocular surgery is contemplated.

Actin filament localization in developing and pathologic human corneas.

Actin is associated with motility, cell morphology, and cell-substrate adhesion. The molecular probe NBD phallacidin, which reacts with filamentous actin, was used to study the distribution of actin filaments in the corneal and conjunctival epithelium, stroma, and endothelium. Frozen sections of human fetal eyes from 8 weeks to 40 weeks of gestation were reacted with NBD phallacidin. Pathologic tissues included keratoplasty specimens from patients with hereditary posterior polymorphous corneal dystrophy (PPMD) and surgically excised tissues removed for treatment of epithelial down-growth. Normal human cornea was used as a control. Immunofluorescent staining disclosed actin filament distribution in corneal epithelium as early as 9-10 weeks of gestation. Staining increased with maturation until term. Adult human corneal epithelium showed more pronounced staining of the surface layers. Stromal staining was more extensive in earlier stages of gestation and decreased in later stages of gestation, after 20-21 weeks. In pathologic corneas with posterior polymorphous dystrophy, there was localization of actin, as well as keratin, in the abnormal epithelial-like layers lining the posterior cornea. In epithelial downgrowth, actin and keratin were demonstrated in multilayered squamous epithelium on the anterior iris surface. Actin appears to be involved in migration of corneal epithelial and endothelial cells.

Clinical, Electron Microscopic, and Immunohistochemical Study of the Corneal Endothelium and Descemet's Membrane in the Iridocorneal Endothelial Syndrome

Two women with the iridocorneal endothelial syndrome had unilateral corneal edema, iris stromal atrophy, and glaucoma. Each underwent penetrating keratoplasty. Transmission electron microscopy of the corneal buttons disclosed a thin, normally structured Descemet's membrane bounded posteriorly by a posterior collagenous layer that contained banded and fibrillar tissue, indicating that the disorder was acquired after childhood. Scanning electron microscopy showed some degenerated corneal endothelial cells with filopodial cytoplasmic projections, suggesting endothelial migration. Transmission electron microscopy of the endothelium showed no signs of epithelial-like alteration, such as stratification, desmosomal junctions, or increased cytoplasmic fibrils. Immunohistochemical staining of fresh-frozen sections with monoclonal antibodies to keratin showed normal staining of the epithelium and no staining of the endothelium. Occasional lymphocytes were seen within the endothelium in one case but were also observed in one case of an inherited corneal disease, posterior polymorphous dystrophy, suggesting that they might be normal "passenger" cells migrating in the endothelial monolayer.

Penetrating Keratoplasty in Children

Retrospectively studied were 91 patients, 14 years of age or less, who had 152 penetrating keratoplasties in 107 eyes, with an average followup of 30.1 months. Survival analysis showed the probability of obtaining a clear graft at one year to be 60 ± 8% in 45 eyes with congenital opacities, 70 ± 8% in 31 eyes with opacities from trauma and 73 ± 8% in 31 eyes with acquired nontraumatic opacities. Most failures occurred during the first postoperative year and were characterized by the gradual loss of graft clarity from undetermined cause. Twenty-nine percent (10) of the 34 eyes with congenital corneal opacities in which vision could be measured had a most recent visual acuity better than 6/120 (20/400). Irreversible amblyopia, glaucoma, other structural abnormalities of the anterior segment and mental retardation complicated visual rehabilitation in the congenital group. In the post-traumatic group, vision was better than 6/120 (20/400) in 45% (13) of 29 eyes, being limited by vitreoretinal pathology, fibrous ingrowth, and optic nerve damage from glaucoma. Visual acuity in the acquired, nontraumatic group was better than 6/120 (20/400) in 67% (20) of 30 eyes. The percentage of patients achieving 6/12 (20/40) or better in the congenital, post-traumatic, and nontraumatic groups were 3% (1/34), 17% (5/29), and 47% (14/30), respectively. In the congenital group, only patients with posterior polymorphous dystrophy obtained a visual acuity of 6/30 (20/100) or better. Preoperative vascularization of the cornea, persistent epithelial defects, and performance of lensectomy-vitrectomy were factors most highly correlated with poor graft survival. Vitrectomy and postoperative aphakia were factors most highly correlated with poor final visual acuity. The data indicate that penetrating keratoplasty is becoming increasingly successful in children and suggest that future efforts should be aimed toward reducing the period of visual deprivation and providing more effective amblyopia therapy.

Posterior Polymorphous Dystrophy of the Cornea

The family of a patient manifesting posterior polymorphous dystrophy, (PPMD), of the cornea was investigated to determine the genetic characteristics and clinical expression of the condition.

Open-angle Glaucoma Associated with Posterior Polymorphous Dystrophy: A Clinicopathologic Study

Clinical and histopathologic features of a 62-year-old black man with posterior polymorphous dystrophy and open-angle glaucoma requiring trabeculectomy are reported. The surgical procedure was modified to allow en bloc resection of the deep limbal tissue and peripheral iris. Light and electron microscopy of the specimen revealed a high insertion of the iris into the posterior portion of the trabecular meshwork with compression of the intertrabecular spaces. These findings are similar to changes that have been reported in primary congenital glaucoma and suggest a developmental anomaly of the anterior chamber angle in this form of glaucoma associated with posterior polymorphous dystrophy.

The Contralateral Eye in the Iridocorneal Endothelial (ICE) Syndrome

Examination of six cases of iridocorneal endothelial (ICE) syndrome revealed that all the patients had subclinical abnormalities in the fellow eye. Of the six, four patients had iris transillumination, four patients had significantly decreased outflow facility but without elevation of intraocular pressure, and all patients had corneal endothelial changes as noted by specular microscopy. The asymmetric rather than unilateral involvement and the similar histopathology to posterior polymorphous dystrophy suggested that these two diseases may share a common pathogenesis. The occurrence of features of Rieger's syndrome and Axenfeld's anomaly in association with posterior polymorphous dystrophy suggested the hypothesis that all these diseases may be characterized by abnormalities of tissues derived from neural crest cells. A unifying hypothesis is presented to explain this group of diseases involving the endothelial cells lining the anterior chamber, namely corneal and trabecular meshwork endothelium, anterior iris stroma and iris melanophores.

CONGENITAL ANTERIOR SEGMENT EPITHELIALISATION (CASE)

Posterior polymorphous endothelial dystrophy and iridocorneal endothelial syndrome share common specular microscopic findings, clinical course, and some histopathological features. Despite differences in inherited trait and severity of disease a common pathogenetic mechanism for the two diseases is suggested. This consists of congenital epithelialisation of the posterior corneal surface during embryogenesis with migration of these cells around the anterior segment uninhibited by surrounding normal endothelium.

Endothelveränderungen bei hinterer polymorpher Hornhautdystrophie

Posterior polymorphous dystrophy of the cornea (Schlichting) was found in a 51-year-old male. In addition, the patient had a cerulean cataract and myopia. The PPD, which was thought to have been caused by endothelial degeneration, exhibited extremely variable expressivity. Of the patient's 3 children only the 19-year-old son, who is also myopic, has cerulean cataract; on specular microscopic examination he was also found to be suffering from endothelial changes.

Clinical Specular Microscopy of Posterior Polymorphous Endothelial Dystrophy

By means of clinical specular microscopy in 27 patients with posterior polymorphous corneal endothelial dystrophy diagnosed by slit lamp examination and 26 relatives with normal findings by slit-lamp and specular microscopic examinations, we identified two clinical and specular microscopic patterns of posterior polymorphous dystrophy. (1) The localized vesicular or band pattern consisted of clear corneas with localized lesions resembling craters that were lined by abnormal cells and surrounded by enlarged, pleomorphic cells. (2) The geographic pattern was associated with Descemet's membrane haze and deep stromal haze, occasional peripheral iridocorneal adhesions, and glaucoma. By specular microscopy, this type had large, well circumscribed areas of abnormal pleomorphic cells with indistinct borders and increased reflective highlights. These areas were surrounded by normal-sized and smaller polygonal cells. The former cells appear to represent epithelial cells and the latter endothelial cells.

Clinical Specular Microscopic/Pathologic Correlation

Abnormal morphology seen by specular microscopy in two corneas was correlated with scanning electron microscopy of the same corneas. In one patient with posterior polymorphous endothelial dystrophy, the bizarre specular microscopic cell appearances appear due to varying densities of surface microvillous projections. In one simian cornea, a localized area of intracellular, pigmented refractile particles by specular microscopy is seen to be the result of melanosomes in an iris pigment epithelial cell in the endothelial layer.

The Differential Diagnosis of Descemet's Tears (Haab's Striae) and Posterior Polymorphous Dystrophy Bands: A Clinicopathologic Study

Band-like structures, clinically similar to Haab's striae, occur in posterior polymorphous dystrophy (PPMD) and are often confused with them. The difference in clinical appearance based on difference in histopathology allows a clear differentiation. The edge of Haab's striae are thickened, curled, and secondarily proliferate Descemet's membrane, while the area between the edge is thin and smooth. Posterior polymorphous dystrophy bands are the exact opposite. The band is a thickening of Descemet's membrane between the edges with thinner, more normal Descemet's membrane outside of them. PPMD bands may be associated with typical vesicles or appear as the only sign of dystrophy, even in the eyes of patients with a known family history.

Similarities between Posterior Polymorphous and Congenital Hereditary Endothelial Dystrophies

Histopathologic study of 14 keratoplasty specimens in 11 cases of posterior corneal dystrophy was performed by light and electron microscopy. Prior clinical diagnosis was congenital endothelial dystrophy (CED) in nine specimens, posterior polymorphous dystrophy (PPD) in three specimens, and posterior corneal dystrophy (PCD) in two specimens. Retrocorneal fibrous tissue proliferation and multilaminated basement membrane were observed in 13 of the 14 specimens. Two or more types of cells lined the posterior surface of the cornea in 12 of the 14 specimens. These cells included: normal-appearing endothelial cells, embryonic-like endothelial cells, degenerated endothelial cells, fibrocyte-like cells, epithelial-like cells, and melanocyte-like cells. Total absence of a cellular layer was observed in one specimen. Because some of the ultrastructural features of CED and PPD are the same, it is possible that these two entities represent a spectrum of the same process.

Posterior polymorphous dystrophy of the cornea: Cell culture studies

Four corneal buttons were obtained as keratoplasty specimens from patients with posterior polymorphous dystrophy (PPMD) of the cornea. Scanning and transmission electron microscopy of cell cultures of corneal endothelial cells revealed the presence of epithelial-like cells as well as ‘normal’ endothelial cells. The epithelial-like cells displayed myriad microvillus projections, stratification, desmosomal junctions and 8 nm cytoplasmic filaments. Indirect immunofluorescent staining of the PPMD corneal sections and cell cultures with antisera prepared against total human epidermal keratins disclosed areas of staining corresponding to the epithelial-like cells observed by electron microscopy and dark nonstaining areas corresponding to ‘normal’ endothelial cells.

Scanning Electron Microscopy of Posterior Polymorphous Corneal Dystrophy

An 8 1/2-year-old girl had posterior polymorphous dystrophy that required keratoplasty. Similar lesions were found in the patient's mother, thus establishing the genetic trend of the disease. Scanning electron microscopy studies showed areas of endothelial cell degeneration and multiple depressions or pits. These seemed the most advanced and characteristic lesions of posterior polymorphous dystrophy. Transmission electron microscopy studies in areas adjacent to the pits showed an abnormally developed Descemet's membrane covered by two or more layers of elongated endothelial-like cells. Cells over Descemet's membrane seemed to deposit some Descemet's membrane material and both fine and coarse collagen fibrils. Cells had prominent mitochondria, normal endoplasmic reticulum, and desmosomal attachments. Cytoplasmic fibrils and microvilli were usually found in cells lining the anterior chamber. Specular microscopy and scanning electron microscopy recorded the image of only the innermost cells and these appeared as endothelium.

Additional Reference on Polymorphous Dystrophy

To the Editor. —In the September 1977 issue of theArchives(95:1529-1537), we published a paper on posterior polymorphous dystrophy. bibliography did not include the excellent work of Dr Merrill Grayson entitled: The Nature of Hereditary Deep Polymorphous Dystrophy of the Cornea: Its Association With Iris and Anterior Chamber Dysgenesis, which appeared in the Transactions of the American Ophthalmological Society (72:516-559, 1974). We apologize for this error, especially since Dr Grayson was so kind as to let us read the manuscript before his work was published. Certainly Dr Grayson's outstanding contribution should be a part of any discussion of posterior polymorphous dystrophy.

Posterior polymorphous dystrophy: a light and electron microscopic study.

Microscopic study of a keratoplasty specimen in a case of posterior polymorphous dystrophy demonstrated via serial sections a multilaminar Descemet's membrane with focal fusiform nodular protrusions of connective tissue. The latter are thought to represent the polymorphous lesions of the posterior limiting layers of the cornea seen clinically. Ultrastructurally, fibroflast-like cells lined the posterior surface of the cornea. It is postulated that those reported cases of PPD in which epithelial-like transformation of the endothelial layer has been described may represent more advanced cases, in which corneal oedema is likely to be a prominant feature clinically. An evolving process of metaplasia rather than a static one might explain the variety of altered endothelial cells, fibroblasts, and epithelial cells which have been reported on the posterior cornea in the few PPD keratoplasty specimens studied to date.

Posterior polymorphous keratopathy.

Seven cases with posterior polymorphous changes of the cornea are reported. After clinical and pathological examination of the above cases, as well as a short review of the literature, the following points are made: (1) Some cases are congenital, being either familial or sporadic, but others are acquired. (2) The term "posterior polymorphous keratopathy" covers all the variants of the condition and is preferred to the traditional "posterior polymorphous dystrophy". (3) The congenital type is a mild variant of the mesodermal dysplasia, whereas the acquired type follows local disease. (4) The condition can be static, but over 50% of cases are slowly progressive, calling for penetrating keratoplasty.

The Clinical Spectrum of Posterior Polymorphous Dystrophy

We examined 61 affected members of eight families with an inherited corneal dystrophy. The corneal abnormalities varied greatly from one member of a family to another. Some patients had only a few isolated endothelial vesicles, while others in the same family had severe secondary stromal and epithelial edema. In some patients edema was present at birth or in early childhood; in others it developed later in life. The wide variation of corneal abnormalities suggests the possibility that several conditions previously described as separate disease entities, such as grouped vesicles, Schnyder's posterior herpes, posterior polymorphous dystrophy, and congenital hereditary endothelial dystrophy, are part of the clinical spectrum of expression of a single familial corneal dystrophy. Some affected family members also had ocular hypertension or open-angle glaucoma. Broad iridocorneal adhesions were present in some of the patients with glaucoma and in others with normal intraocular pressures. Other ocular abnormalities present in a few patients include pupillary ectropion, "glass membranes" on the anterior iris surface, and bands in Descemet's membrane. The transmission in most of the families was autosomal dominant. In two families it appeared to be autosomal recessive.