Posterior Polymorphous Dystrophy Research Articles

Penetrating keratoplasty in infants

Purpose: To analyze graft survival and visual outcome after penetrating keratoplasty in infants with congenital corneal opacity. Methods: We retrospectively reviewed the records of 11 patients with congenital corneal opacity who underwent penetrating keratoplasty as infants. Six patients had a diagnosis of Peter's anomaly, 1 of congenital hereditary endothelial dystrophy, 1 of posterior polymorphous dystrophy, and 2 of sclerocornea, and in the other patient, the cause of the opacity was unknown. Results: In total, 26 penetrating keratoplasties were performed on 16 eyes of 11 infants. All patients initially underwent surgery before the age of 13 months. Five patients underwent bilateral penetrating keratoplasty, and 10 of the transplants were repeat operations on eyes that had already had at least one previously failed graft. The age of the infants at the time of first penetrating keratoplasty ranged from 2 to 56 weeks (median, 13 weeks). The graft survival time for all transplants ranged from 3 to 137 months (median, 16 months). Overall first graft survival at 12 months was 61% (95% CI, 33%-81%), with 10 of 16 eyes retaining a clear corneal graft. Peter's anomaly, lensectomy, and repeat penetrating keratoplasty were factors most highly associated with poor graft survival and a low final visual acuity. Conclusion: Early penetrating keratoplasty for congenital corneal opacity may prevent deprivation amblyopia. Although this procedure carries a high risk of failure, particularly in those patients with Peter's anomaly, careful case selection, optical correction, and management of postoperative amblyopia may result in a successful visual outcome. (J AAPOS 2001;5:285-90)

Posterior Polymorphous Membranous Dystrophy With Overlapping Features of Iridocorneal Endothelial Syndrome

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Terrienʼs Marginal Degeneration Associated with Posterior Polymorphous Dystrophy

Terrienʼs Marginal Degeneration Associated with Posterior Polymorphous Dystrophy

Exclusion of AR-CHED from the chromosome 20 region containing the PPMD and AD-CHED loci

Congenital hereditary endothelial dystrophy (CHED) is a disorder of the corneal endothelium and has been recognized to segregate in families with both autosomal dominant (AD) and autosomal recessive (AR) modes of transmission. AD-CHED has been previously linked to the pericentric region of chromosome 20. Posterior polymorphous dystrophy (PPMD), a corneal endothelial disorder showing phenotypic overlap with CHED, has also been previously genetically mapped to this region. The genetic interval containing AD-CHED is within the larger genetic interval containing the PPMD locus. This study sought to determine whether AR-CHED segregating in a consanguineous Saudi Arabian pedigree is linked to the previously mapped and overlapping loci for AD-CHED and PPMD on the pericentric region of chromosome 20. Forty members of a consanguineous Saudi Arabian pedigree segregating AR-CHED were ascertained. Short tandem-repeat polymorphic markers from the 20 cM interval on chromosome 20 containing both the PPMD and AD-CHED loci were used to genotype these individuals. LOD score analysis of the genotype data with the MENDEL software package utilizing a model of autosomal recessive inheritance with complete penetrance showed exclusion of CHED from the entire PPMD/AD-CHED interval by utilizing overlapping intervals of LOD scores of at least -2. The results obtained demonstrate that AR-CHED is not allelic to either AD-CHED or PPMD, although it has been proposed that AD-CHED may be allelic to PPMD. Thus, there are at least two genes responsible for CHED and PPMD.

Homozygosity mapping and linkage analysis demonstrate that autosomal recessive congenital hereditary endothelial dystrophy (CHED) and autosomal dominant CHED are genetically distinct

BACKGROUNDCongenital hereditary endothelial dystrophy (CHED) is a corneal dystrophy characterised by diffuse bilateral corneal clouding resulting in impaired vision. It is inherited in either an autosomal dominant (AD) or autosomal...

Posterior polymorphous dystrophy associated with posterior amyloid degeneration of the cornea

PURPOSE: To describe a case of posterior polymorphous dystrophy associated with posterior amyloid degeneration of the cornea confirmed histopathologically and immunohistochemically. METHODS: An 80-year-old woman with corneal opacities required penetrating keratoplasty. The keratectomy specimen was evaluated by light microscopy and immunohistochemistry. RESULTS: Microscopic examination of the keratectomy specimen showed scattered fusiform deposits located in the deep corneal stroma. Congo red stains of the fusiform deposits confirmed the diagnosis of amyloidosis. Immunohistochemical stains for cytokeratin (AE1/AE3) showed that the endothelial cells were immunoreactive, confirming the diagnosis of posterior polymorphous dystrophy. CONCLUSIONS: To our knowledge, the association between posterior polymorphous dystrophy and posterior amyloid degeneration has not been reported previously.

Structure, development and function of cytoskeletal elements in non-neuronal cells of the human eye.

The cytoskeleton, of which the main components in the human eye are actin microfilaments, intermediate filaments and microtubules with their associated proteins, is essential for the normal growth, maturation, differentiation, integrity and function of its cells. These components interact with intra- and extracellular environment and each other, and their profile frequently changes during development, according to physiologic demands, and in various diseases. The ocular cytoskeleton is unique in many ways. A special pair of cytokeratins, CK 3 and 12, has apparently evolved only for the purposes of the corneal epithelium. However, other cytokeratins such as CK 4, 5, 14, and 19 are also important for the normal ocular surface epithelia, and other types may be acquired in keratinizing diseases. The intraocular tissues, which have a relatively simple cytoskeleton consisting mainly of vimentin and simple epithelial CK 8 and 18, differ in many details from extraocular ones. The iris and lens epithelium characteristically lack cytokeratins in adults, and the intraocular muscles all have a cytoskeletal profile of their own. The dilator of the iris contains vimentin, desmin and cytokeratins, being an example of triple intermediate filament expression, but the ciliary muscle lacks cytokeratin and the sphincter of the iris is devoid even of vimentin. Conversion from extraocular-type cytoskeletal profile occurs during fetal life. It seems that posttranslational modification of cytokeratins in the eye may also differ from that of extraocular tissues. So far, it has not been possible to reconcile the cytoskeletal profile of intraocular tissues with their specific functional demands, but many theories have been put forward. Systematic search for cytoskeletal elements has also revealed novel cell populations in the human eye. These include transitional cells of the cornea that may represent stem cells on migration, myofibroblasts of the scleral spur and juxtacanalicular tissue that may modulate aqueous outflow, and subepithelial matrix cells of the ciliary body and myofibroblasts of the choroid that may both participate in accommodation. In contrast to the structure and development of the ocular cytoskeleton, changes that take place in ocular disease have not been analysed systematically. Nevertheless, potentially meaningful changes have already been observed in corneal dystrophies (Meesmann's dystrophy, posterior polymorphous dystrophy and iridocorneal endothelial syndrome), degenerations (pterygium) and inflammatory diseases (Pseudomonas keratitis), in opacification of the lens (anterior subcapsular and secondary cataract), in diseases characterized by proliferation of the retinal pigment epithelium (macular degeneration and proliferative vitreoretinopathy), and in intraocular tumours (uveal melanoma). In particular, upregulation of alpha-smooth muscle actin seems to be a relatively general response typical of spreading and migrating corneal stromal and lens epithelial cells, trabecular cells and retinal pigment epithelial cells.

Extrusion of Abnormal Endothelium into the Posterior Corneal Stroma in a Patient with Posterior Polymorphous Dystrophy

To report the presence of abnormal endothelium that extruded into the posterior corneal stroma in a patient with posterior polymorphous dystrophy. The corneal button of a man who underwent penetrating keratoplasty for posterior polymorphous dystrophy was examined by light and electron microscopy. Immunoperoxidase staining for cytokeratins, vimentin, and the endothelial antigen recognized by monoclonal antibody 2B4.14.1 antigen was performed. Two-color immunofluorescence staining for simultaneous detection of cytokeratins and 2B4.14.1 antigen was also done. Much of the endothelium had characteristic features of epithelium-like cells, and abnormalities in Descemet's membrane were present. Curious oval and slit-like spaces in the posterior stroma were lined by epithelium-like endothelial cells and were continuous with the anterior chamber through defects in Descemet's membrane. These abnormalities in the posterior stroma have not previously been described in histopathologic reports of posterior polymorphous corneal dystrophy and are likely an unusual variation in the spectrum of this hereditary disorder.

Rupture of Descemet's membrane secondary to presumed forceps trauma

Ruptures in Descemet's membrane can occur secondary to forceps injury at birth, prolonged labor, blunt trauma, keratoconus, and congenital glaucoma as well as other less frequent causes. The rupture initially causes acute comeal hydrops which resolves within weeks to leave permanent linear thickening of Descemet's membrane. It is important to differentiate Descemet's rupture from other entities like syphilitic interstitial keratitis, posterior polymorphous dystrophy and congenital hereditary endothelial dystrophy which may have a similar clinical presentation. Although treatment is rarely required, proper diagnosis is important to prevent unnecessary referrals and provide appropriate counseling. This case report examines a 66-year-old female with Descemet's rupture secondary to presumed forceps trauma at birth. Discussion of clinical presentation, differential diagnosis and clinical management are presented.

Clinical and Histopathologic Features of Corneal Dystrophies in Japan

To examine retrospectively the frequency of various corneal dystrophies among Japanese patients who underwent keratoplasty or keratectomy at the authors' institution over a 34-year period, and to compare the histopathologic features of these disorders in the Japanese population with those reported in the Western literature. Corneal specimens obtained during keratectomy or keratoplasty (lamellar and penetrating) performed at the authors' institution from 1959 through 1992 were reviewed. Immunohistochemical studies were performed using monoclonal antibodies to keratan sulfate and gelsolin, as well as two lectins (concanavalin A and wheat germ agglutinin). Of 1259 corneal specimens, 159 (12.6%) specimens from a total of 80 patients showed corneal dystrophy. Virtually all were non-Fuchs dystrophies; only one case of primary Fuchs dystrophy was identified histologically. Granular dystrophy and gelatinous drop-like dystrophy were the most common dystrophies identified in the specimens, largely because of multiple specimens from individual patients with recurrent disease. These two disorders accounted for 86 of the 159 specimens. In terms of numbers of patients, lattice dystrophy was the most common (26 patients, 32.5%), followed by macular dystrophy (16 patients, 20%), gelatinous drop-like dystrophy (15 patients, 18.8%), granular dystrophy (14 patients, 17.5%), and Avellino dystrophy (3 patients, 3.75%). Dystrophies represented by only one or two patients included congenital hereditary endothelial dystrophy, primary spheroidal keratopathy, posterior polymorphous dystrophy, Schnyder crystalline dystrophy, and Fuchs dystrophy. This histopathologic study showed a very low incidence of Fuchs dystrophy in the authors' Japanese patient population, compared with the incidences seen in studies of populations in Western countries. Of the non-Fuchs dystrophies, lattice dystrophy was the most common among the patients, although there were large numbers of specimens with granular dystrophy and gelatinous drop-like dystrophy due to their recurrent character. The causes of clinical and histopathologic differences and similarities among the Japanese patients and the patients described in the Western literature are likely related to genetic factors, but a complete understanding of their specific mechanisms awaits future molecular biologic and genetic elucidation.

Linkage of posterior polymorphous corneal dystrophy to 20q11.

Posterior polymorphous dystrophy (PPMD) is an autosomal dominant disorder of the cornea that is clinically recognized by the presence of vesicles on the endothelial surface of the cornea. The corneal endothelium is normally a single layer of cells that lose their mitotic potential after development is complete. In PPMD, the endothelium is often multi-layered and has several other characteristics of an epithelium including the presence of desmosomes, tonofilaments, and microvilli. These abnormal cells retain their ability to divide and extend onto the trabecular meshwork to cause glaucoma in up to 40% of cases. A large family with 21 members affected with PPMD was genotyped with short tandem repeat polymorphisms distributed across the autosomal genome. Linkage was established with markers on the long arm of chromosome 20. The highest observed LOD score was 5.54 (theta = 0) with marker D20S45. Analysis of recombination events in four affected individuals revealed that the disease gene lies within a 30cM interval between markers D20S98 and D20S108.

Linkage of congenital hereditary endothelial dystrophy to chromosome 20.

Congenital heredity endothelial dystrophy (CHED) is a rare autosomal dominant disorder of the cornea. We have performed genetic linkage analysis with microsatellite markers on a seven generation British pedigree. Two-point linkage analysis revealed significant linkage of CHED (lod score >3) with seven marker loci mapping to chromosome 20. The highest observed lod score was 7.20 (theta=0.026) with marker D20S114. Multipoint analysis gave a maximum lod score of 9.34 between D20S48 and D20S471. This 2.7cM region lies within 30 cM region recently assigned to posterior polymorphous dystrophy (PPD). PPD and CHED may therefore be allelic, or alternatively it is possible that more than one gene in this region is responsible for these two corneal dystrophies.

An Ultrastructural Investigation of an Early Manifestation of the Posterior Polymorphous Dystrophy of the Cornea

Posterior polymorphous dystrophy of the cornea is an uncommon, but well-recognized, congenital disease affecting Descemet's membrane and endothelium. Visual impairment usually is minimal and slowly progressive. Edema develops in a small number of patients, necessitating a corneal graft in middle age. An early manifestation of posterior polymorphous dystrophy with corneal edema present at birth or soon thereafter is extremely rare; only a few ultrastructural reports are available. The corneal button of a 5-month-old baby with posterior polymorphous dystrophy was examined by conventional light and electron microscopy. The anterior banded zone of Descemet's membrane was thinned (2 microns) in the axial part of the cornea, contained defects in the paraxial part, and was absent at the periphery. Where present, the anterior banded zone was lined posteriorly by a fibrocellular layer (containing fibroblast-like spindle cells and striated collagen fibrils) and a fibrillar layer forming an abnormal posterior collagenous layer. This layer was lined posteriorly by degenerate overlapping endothelial cells, which also were in apposition to the stroma in regions with an absent anterior banded zone. The defects in Descemet's membrane were used by the abnormal keratocytes to migrate between the anterior banded zone and the posterior collagenous layer. At the periphery, a multilayer of spindle cells was present behind the stroma. Failure to produce a continuous anterior banded zone indicates an onset of the disease before the twelfth week of gestation. It appears that, in posterior polymorphous dystrophy, there is a mosaic of better preserved and dystrophic endothelial cells and that the presence or absence of the normal components of Descemet's membrane is determined by the proportion of dystrophic cells in the endothelial cell population.

Epithelial Transformation of the Corneal Endothelium in Forceps Birth-Injury-Associated Keratopathy

Using light and electron microscopy, we studied four keratectomy specimens obtained by penetrating keratoplasty from four patients (ages 33-54 years; mean age: 43 years old) who had clinical evidence of Descemet's folds and bullous keratopathy after ruptures in Descemet's membrane after forceps injury at birth. Histopathologically, three patients showed the typical features of forceps birth injury: Descemet's membrane at the margin of the rupture was folded and assumed a scroll-shape configuration. The fourth patient showed clusters of proliferated endothelial cells at the site of two ruptures, and from one site of the ruptures, these cells invaded into Descemet's membrane, forming a new basement membrane. Transmission electron microscopy revealed that these proliferated cells were epithelial-like cells characterized by desmosomal junctions, basal lamina, numerous microvilli, and 8-nm cytoplasmic filaments. The epithelial transformation of the corneal endothelium was identified in cases of posterior polymorphous dystrophy and assumed to be specific for this entity. The findings in our fourth patient represent the first documentation of epithelial-like cells on the posterior corneal surface in forceps birth-injury-associated keratopathy. Our results suggest that epithelial transformation may be a nonspecific reaction of the young cornea to various stimuli.

Corneal dystrophies

Basic science research on the corneal dystrophies is uncovering information indicating that these disorders may not all be solely corneal abnormalities. The presence of a systemic disorder may help to explain the high incidence of recurrence of certain corneal dystrophies after penetrating keratoplasty. Recent advances in stromal and crystalline corneal dystrophies and posterior polymorphous dystrophy are discussed, along with evaluation of the posterior corneal anatomy with specular microscopy. Current Opinion in Ophthalmology 1992, 3:438-444

Bilateral Progressive Essential Iris Atrophy and Keratoconus with Coincident Features of Posterior Polymorphous Dystrophy

We report the first case known to us of an apparent bilateral association of essential iris atrophy (EIA) and keratoconus (KC), with coincident features of posterior polymorphous dystrophy (PPD). Based on this case and the published natural history and findings of both the irido corneal endothelial (ICE) syndrome and PPD, we propose a new hypothesis for the pathogenesis of the ICE syndrome with associated KC and/or PPD. We suggest that, similar to the genetics of retinoblastoma, the predisposition for either the ICE syndrome or for PPD is inherited as an inactive allele, the so-called “first hit.” Inactivation of the second allele, or “second hit,” which could occur at any time, might be the product of the background mutation rate or of an environmental trigger. Dedifferentiation or an abnormality in normal development could occur after the first or second hit, resulting in varying clinical patterns. We also concur with other investigators that PPD could be part of the spectrum of the ICE syndrome, owing to similarities in their clinical presentations, histopathology, specular and electron microscopy, and natural history.

Bilateral Progressive Essential Iris Atrophy and Keratoconus with Coincident Features of Posterior Polymorphous Dystrophy

We report the first case known to us of an apparent bilateral association of essential iris atrophy (EIA) and keratoconus (KC), with coincident features of posterior polymorphous dystrophy (PPD). Based on this case and the published natural history and findings of both the irido corneal endothelial (ICE) syndrome and PPD, we propose a new hypothesis for the pathogenesis of the ICE syndrome with associated KC and/or PPD. We suggest that, similar to the genetics of retinoblastoma, the predisposition for either the ICE syndrome or for PPD is inherited as an inactive allele, the so-called "first hit." Inactivation of the second allele, or "second hit," which could occur at any time, might be the product of the background mutation rate or of an environmental trigger. Dedifferentiation or an abnormality in normal development could occur after the first or second hit, resulting in varying clinical patterns. We also concur with other investigators that PPD could be part of the spectrum of the ICE syndrome, owing to similarities in their clinical presentations, histopathology, specular and electron microscopy, and natural history.

Posterior Polymorphous Dystrophy and Alport Syndrome

Abstract: Seventeen Thai patients from nine families with Alport syndrome underwent complete ocular examination and specular microscopy. Fourteen (82.3%) patients had ocular changes. Eleven (64.7%) had endothelial vesicles compatible with posterior polymorphous dystrophy. Four of these also had subepithelial opacities, a previously undescribed phenomenon. Other ocular changes included lenticonus and macular and midperipheral retinal flecks. A second group of 18 consecutive patients from 14 families with posterior polymorphous dystrophy detected during routine ocular examination underwent renal evaluation. Five had hematuria, four of whom had sensorineural hearing loss. Two of the four patients also had characteristic renal biopsy findings. Another had sensorineural hearing loss without hematuria, and renal biopsy showed a thin glomerular basement membrane. Posterior polymorphous dystrophy is a common but frequently overlooked finding in Alport syndrome. The frequent association of these two hereditary conditions suggests a common defect in basement membrane formation. Patients with posterior polymorphous dystrophy should be examined for renal abnormalities and hearing loss.

The Posterior Corneal Surface in Posterior Polymorphous Dystrophy: A Specular Microscopical Study

Forty-eight cases of posterior polymorphous dystrophy (PPD), diagnosed on the presence of classic vesicles at the level of Descemet's membrane, were studied with the specular microscope. Vesicles alone occurred in 42% and were present in conjunction with PPD bands in 48% and a diffuse abnormality of Descemet's membrane in 10%. It was notable that none of the cases showed ocular abnormalities other than those of the cornea. Endothelial specular photomicroscopy (ESP) revealed distinctive characteristics of PPD vesicles and bands that distinguish them from other posterior corneal abnormalities, e.g., the iridocorneal endothelial syndrome and Haab's striae, which can appear similar at the slit lamp level. The interpretation of the ESP images was that vesicles are pits and bands are trenches in Descemet's membrane only. The endothelium was composed of enlarged cells in almost all cases. Other endothelial abnormalities reported by previous observers were not found. There was evidence that the affected corneas of children were more rigid than normal, and this is discussed in relation to the aetiology of the lesions of PPD.

Recurrence of Posterior Polymorphous Corneal Dystrophy After Penetrating Keratoplasty

Recurrence of a corneal dystrophy after keratoplasty can occur in multiple dystrophies, including macular, granular, and lattice dystrophies. We treated two unrelated patients who had documented posterior polymorphous dystrophy and who, in previously clear grafts, developed haziness in the zone of Descemet's membrane, which led to graft failure. Histologic examination of the keratoplasty specimen showed changes typical of posterior polymorphous dystrophy.