Walter Lisch

Schnyder's dystrophy Progression and metabolism

In the first long-term cohort study of Schnyders corneal dystrophy the authors examined affected and unaffected members of two unrelated families in 1975 and 1976 respectively, and again in 1984. They identified carriers, catalogued changes in the diffuse and crystalline corneal opacities which characterize this dystrophy and analysed the patients lipid metabolism. Corneal opacities never regressed. Progression was more frequent in diffuse than in crystalline opacities. Both crystalline and diffuse opacities reappeared and progressed following penetrating keratoplasty. Mean cholesterol levels in the carrier group were above normal and six had a moderate type IIa dyslipoproteinemia; conversely, two carriers had low apo B. The degree of corneal opacification showed no relationship to dyslipoproteinemia. Schnyders corneal dystrophy appears to involve the corneal lipid metabolism only and not to be a systemic disease.

Lisch corneal dystrophy is genetically distinct from Meesmann corneal dystrophy and maps to Xp22.3

PURPOSEnThere is an ongoing discussion whether Lisch corneal dystrophy (band-shaped and whorled microcystic dystrophy of the corneal epithelium) represents a disorder that is different from Meesmann corneal dystrophy. The purpose of this study was to evaluate at the molecular level if Lisch and Meesmann corneal dystrophies are genetically distinct.nnnMETHODSnWe examined at the slit lamp a total of 48 members of a family with an aggregation of Lisch corneal dystrophy. Genomic DNA was extracted from leukocytes of the peripheral blood of seven affected and six unaffected members of this family. Mutational hotspots in the cornea-specific keratin genes K3 and K12 were scanned for mutations by single-strand conformation analysis. To test for linkage to the keratin K3 or K12 loci or for X-chromosomal inheritance, six (K3) and four (K12) microsatellite markers each flanking the keratin loci as well as 22 microsatellite markers covering the X-chromosome were typed. Linkage was analyzed using the MLINK and FASTMAP procedures.nnnRESULTSnA total of 19 trait carriers were identified in six generations of the family. No hereditary transmission from father to son was observed. Linkage was excluded for the keratin K3 and K12 genes. Furthermore, single-strand conformation analysis detected no mutations in these genes. Multipoint linkage analysis revealed linkage with a maximum likelihood of the odds (LOD) score of 2.93 at Xp22.3. Linkage was excluded for Xp22.2 to Xqter.nnnCONCLUSIONSnLisch corneal dystrophy is genetically different from Meesmann corneal dystrophy. Evidence was found for linkage of the gene for Lisch corneal dystrophy to Xp22.3.

Paraproteinemic Corneal Deposits in Plasma Cell Myeloma

We treated two patients who had IgG-kappa-light chain monoclonal gammopathy with partially crystalline and partially amorphic corneal deposits. Impairment of vision made keratoplasty necessary for each patient. Histologic examination of the corneal specimens showed deposits that stained positively for Massons trichrome in all corneal cells. Immunohistochemical tests identified these deposits as IgG-kappa-light chain immunoglobulin fragments. Electron microscopy showed intracellular, rhomboid-shaped deposits enveloped by a membrane. The same deposits appeared in the conjunctival epithelium, within subconjunctival fibrocytes, and in the plasma cells of the bone marrow. Immunoelectrophoresis showed IgG-kappa-light chain fragments in the blood serum, the lacrimal film, and the aqueous humor. This suggests that the intracellular immunoglobulin fragments may have entered the corneal and conjunctival epithelium by way of the lacrimal film, the keratocytes by way of the corneo-scleral limbus vasculature, and the endothelial cells from the aqueous humor.

Elevated prolactin levels in human aqueous humor of patients with anterior uveitis

Evidence is accumulating that prolactin (PRL) may play a physiological role in the regulation of humoral and cell-mediated immune responses. On the basis of these observations, we measured levels in the serum and aqueous humor of 28 patients with cataract or anterior uveitis with concomitant cataract. Intraocular concentrations were measured in a range from 0.1 to 3.4 ng/ml. whereas serum PRL levels failed to show significant differences between the two groups (P=0.39), intraocular concentrations were significantly higher in uveitis patients (P<0.001). The level in aqueous humor did not reflect the serum concentration in either group. To the best of our knowledge, this is the first study measuring PRL concentrations in human aqueous humor.

Chameleon-like appearance of immunotactoid keratopathy.

Purpose: To demonstrate 5 different patterns of immunotactoid keratopathy (ITK) in monoclonal gammopathy of undetermined significance (MGUS) that can mimic hereditary and degenerative disorders. First follow-up of 1 female patient was performed. Methods: Colored slit-lamp photodocumentation of 6 MGUS light kappa patients with different types of ITK, one patient with a follow-up of 7 years. Systemic and serological examinations of all 6 patients were performed. Results: The systemic and serological examinations disclosed an MGUS light kappa in all 6 patients. The 7-year follow-up of case 2 showed a reduction of lattice-like opacity to moderate diffuse corneal opacity. Corneal opacity patterns of the 6 patients were as follows: pattern 1, crystalline-like; pattern 2, lattice-like; pattern 3, peripheral granular-like; pattern 4, peripheral band-like; and patterns 5 and 6, peripheral patch-like. Conclusions: ITK of MGUS can mimic cystinosis, Schnyder corneal dystrophy (CD), pre-Descemet CD, lattice CD, granular CD, arcus lipoides, lecithin-cholesterol acyltransferase deficiency, gelatinous drop-like CD, and Salzmann nodular degeneration. ITK can be the first symptom of MGUS. An annual internal check of MGUS is recommended because of occurrence of a systemic monoclonal gammopathy in 20% of cases.

Contact lens-induced regression of Lisch epithelial corneal dystrophy.

Purpose: To describe the use of soft contact lenses (CL) to reduce the epithelial opacities of Lisch epithelial corneal dystrophy (LECD). First presentation of confocal microscopy in LECD. Methods: Two unrelated female patients with LECD demonstrated a central gray opacity with distinct visual impairment. The first patient wore a daily hydroxyethlmethacrylate (HEMA) CL for 3 months and the second, a daily silicone hydrogel CL for 1 month. Pre-CL and post-CL appearances of the cornea were photodocumented at the slit lamp. Additionally, in the second patient, a confocal microscopic evaluation of LECD was performed. Results: In both patients, the wearing of CL resulted in a distinct reduction of central corneal opacification with a visual improvement. Discontinued wearing of CL induced again a progression of opacity. The confocal microscopy disclosed the typical intracytoplasmatic vacuolization of the involved epithelial cells. Conclusions: Wearing CL for a longer duration causes a significant regression of corneal opacities in LECD. The etiology of this phenomenon is interpreted as a CL-induced thinning of corneal epithelium and reduction of epithelial layers.

Management of the Opacified Posterior Lens Capsule: An Excision Technique for Membranous Changes

In 16 patients ranging from six months to 85 years a membranous-changed posterior lens capsule was partially excised during an originally extracapsular-planned lens surgery. After removing the lens contents the anterior chamber was filled with sodium hyaluronate. The opacified posterior capsule was punctiformly opened and the retrolenticular space widened with sodium hyaluronate, too. The isolated posterior capsule could be excised with microscissors without damaging the corneal endothelium or the anterior vitreous face. Integrity of the vitreous was preserved in 94% of the operated eyes. The described technique can be regarded as the method of choice for management of solid capsular opacities in infants and may be also helpful in some cases of membranous capsular changes in adults.

Individual phenotypic variances in a family with Thiel-Behnke corneal dystrophy.

To the Editor: We would like to comment on the article “Individual phenotypic variances in a family with Thiel–Behnke corneal dystrophy” by Nakamura et al in the November 2012 issue of the Journal. The aim of the authors was to document the phenotypic variability of family members with 10q-linked “Thiel– Behnke” corneal dystrophy (TBCD) that was first presented by Yee et al in 1997. The authors present 9 affected individuals with different corneal opacity patterns that are also demonstrated in 17 slit-lamp photographs. This article has several drawbacks: First, it is unclear whether some of the opacity patterns in 5 of the 9 patients were shown or evaluated before or after surgical interventions. Ten eyes were listed as having undergone phototherapeutic keratectomy. Recurrences of corneal dystrophies after surgical interventions may or may not be similar to the original opacity pattern. The differential diagnosis of TBCD and Reis–Bücklers corneal dystrophy (RBCD) can be difficult to make especially in the first 2 decades. In a later stage, we see their typical landmarks: a honeycomb-like pattern in TBCD and a geographic-like pattern in RBCD. We consider it misleading that the authors speak about map-like opacities in association with RBCD and TBCD, because map-like rather than geographic-like opacities are one of the 4 landmarks of quite another entity, epithelial basement membrane dystrophy. The RBCD is ultrastructurally characterized by rod-shaped deposits in the corneal epithelium and stroma. In TBCD, a destroyed Bowman layer is replaced by fibrous tissue that accumulates in a very typical sawtooth-like configuration. This tissue is ultrastructurally characterized by “curly fibers” that stain positive for keratoepithelin. In none of the 17 photographs published by Nakamura et al are we able to see a typical honeycomb-like pattern, given the quality of the images, contrary to what the authors mention in the legend of Figures 2 and 3. The photography of the subtle corneal changes was never documented in retroillumination or in the central cornea against the dilated pupil. It would also have been valuable to provide an optical coherence tomography (OCT) scan of the anterior segment of the cornea. Vajzovic et al presented in their Figure 1A a TBCD with the typical honeycomb-like pattern. In Figure 1B, they showed an ultrahigh-resolution anterior segment OCT scan, confirming an extensive sawtooth-like pattern of hyperreflective material deposited along the Bowman layer. Their OCT observation correlated impressively with the histological changes of the TBCD. Nakamura et al mention but did not present any histologic material of the 10q-linked “TBCD.” Finally, Nakamura et al point out that “In the advanced stages of the disease, the accumulation of corneal deposits produces superficial erosions of the eye, leading to substantial secondary scaring.” In our assessment, this interpretation of recurrent erosioninduced scaring is questionable. We challenge it using 2 examples: first, recurrent epithelial erosions represent a frequent symptom of classic lattice corneal dystrophy. However, the occurrence of a diffuse subepithelial haze in the center of the cornea in lattice corneal dystrophy is not because of recurrent erosions but because of the progressive deposition of amyloid. Second, in Franceschetti corneal dystrophy, the clinical symptoms begin in the first decade of life with recurrent attacks of corneal erosions, lasting for decades. After the healing of the erosions, we see a complete recovery of the corneal clarity. Affected individuals get diffuse corneal opacities mostly not earlier than the fourth to fifth decades. The authors do not accurately describe the long-term confusion between RBCD and TBCD in the literature. In 1938, Bücklers described a second form of granular corneal dystrophy, disclosing corneal rings and stars. Later, many authors misinterpreted the honeycomb-like patterns of TBCD as such ring-like changes and diagnosed TBCD as RBCD. For a lack of better evidence, the recent IC3D-classification of corneal dystrophies lumped together the original 5q-linked TBCD and the 10q-linked “TBCD” into one and the same template of TBCD. Unless convincing evidence is presented that the latter phenotype truly conforms to the TBCD phenotype, it no longer seems acceptable to include the dystrophy located on chromosome 10q32-q24 in the TBCD category. Such evidence is not available, in our opinion, in the article by Nakamura et al.

Immunotactoid microtubular corneal deposits in bilateral paraprotein crystalline keratopathy and atypical corneal immunoglobulin deposition in a patient with dysproteinemia.

To the Editor: We have read with interest the article ‘‘Immunotactoid microtubular corneal deposits in bilateral paraprotein crystalline keratopathy’’ published by Singh and the article ‘‘Atypical corneal immunoglobulin deposition in a patient with dysproteinemia’’ published by Matoba et al. Both articles describe the corneal opacifications with regard to a monoclonal gammopathy L-kappa; Dr. Singh disclosed ‘‘peripheral white infiltrate at the limbus in both the eyes’’ and Matoba et al ‘‘bilateral, white, amorphous, cloud-like opacities at the level of deep stroma and temporally in the mid periphery.’’ We were able to see 5 different opacity patterns in benign monoclonal gammopathy L-kappa: crystalline-like, central lattice-like, peripheral granularlike, peripheral band-like, and finally peripheral patches-like (unpublished data). The title of the article by Singh is misleading because the presented patient did not show a crystalline keratopathy. Matoba et al describe the peripheral opacification as atypical, but such alterations are well known in benign monoclonal gammopathy. We need a uniform and internationally accepted nomenclature in the future when we describe the chameleon-like corneal appearance of immunotactoid keratopathy in benign monoclonal gammopathy. As a proposal, the term for the 2 articles: ‘‘Peripheral band-like immunotactoid keratopathy.’’ The term immunotactoid keratopathy represents the different opacity patterns of benign monoclonal gammopathy. The corneal appearance of monoclonal gammopathy is less known because of the different archaic and misleading terms in the past literature.

Linkage analysis in granular corneal dystrophy (Groenouw I), Schnyder's crystalline corneal dystrophy, and Reis-Bücklers' corneal dystrophy.

Tight linkage was excluded for 8 markers in 37 blood relatives from 3 families, 29 of whom had granular corneal dystrophy (Groenouw I). Inconclusive results were obtained for linkage with four marker loci. The highest positive LOD score was 0.57 for linkage between glutamic pyruvic transaminase and granular corneal dystrophy. Tight linkage was excluded for glyoxalase-1 in eight individuals from one family with Schnyders crystalline corneal dystrophy. Results were inconclusive for another six markers. Positive LOD scores were obtained for linkage with adenylate-kinase 1 and the ABO blood group, with values of 1.16 and 0.67, respectively. Among six blood relatives with Reis-Bücklers corneal dystrophy, the highest positive LOD score was 1.17 for linkage with mitochondrial malic enzyme. For another six markers informative for linkage analysis, the results were inconsistent.