In vivo confocal microscopy of Fleck dystrophy and pre-Descemet's membrane corneal dystrophy

PURPOSE: To assess the value of in vivo confocal microscopy (CM) in the diagnosis of Fleck dystrophy and pre-Descemet's membrane corneal dystrophy. METHODS: Case report of two patients. Standard slit-lamp and ophthalmic examination and in vivo CM were performed on both patients. The thickness of the cornea and the morphology of the corneal epithelium, stroma, endothelium, and subbasal nerves were evaluated by confocal microscopy. RESULTS: Biomicroscopy revealed bilateral, fine, dust-, and flour-like opacities in the corneal stroma for the Fleck dystrophy patient. In the pre-Descemet's membrane corneal dystrophy patient, biomicroscopy showed opacities larger than those in the first patient. Both patients were then examined by in vivo CM. Confocal microscopy of the Fleck dystrophy showed intracellular deposits throughout the stroma. In pre-Descemet's membrane corneal dystrophy, however, these and the extracellular deposits were observed immediately anterior to Descemet's membrane. The thicknesses of the corneas were 560 and 650 microm for Fleck and pre-Descemet's membrane corneal dystrophy, respectively. The surface epithelium, subbasal nerves, and endothelium showed normal morphology in both patients. CONCLUSION: In vivo CM is a valuable tool in diagnosing rare corneal dystrophies when the final diagnosis is difficult to obtain with conventional methods.     

In vivo confocal microscopy findings in a patient with posterior amorphous corneal dystrophy

A 21-year-old man, with bilateral posterior amorphous corneal dystrophy, was studied by biomicroscopy, corneal topography and in vivo confocal microscopy. The best-corrected visual acuity was 6/21 in the right eye and 6/6.9 in the left eye. Biomicroscopy revealed bilateral, asymmetric, sheet-like opacification at the deep posterior stromal layer. The corneal topography displayed asymmetric against-the-rule astigmatism in the right eye and prominent steepening at the inferior paracentral cornea in both eyes. In vivo confocal microscopy of the corneas demonstrated microfolds and hyper-reflective layer at the posterior stroma just adjacent to the endothelial layer. The epithelium, Bowman's membrane, anterior stroma and the endothelial layer were normal. In vivo confocal microscopy is useful in evaluating the corneal dystrophies.     

Confocal microscopy in lattice corneal dystrophy

· Background: The purpose of the study was to assess the appearance of lattice corneal dystrophy by means of white-light confocal microscopy. · Methods: Two consecutive patients with lattice corneal dystrophy were prospectively examined. In vivo white-light tandem-scanning confocal microscopy was performed in the right eye of the first patient. Her left eye had undergone penetrating keratoplasty 4 years earlier. Histologic findings of the corneal button were compared with confocal microscopic findings of the right eye. The other patient was monocular and confocal microscopy was performed only in the non-seeing eye. · Results: In both patients, linear and branching structures with changing reflectivity and poorly demarcated margins were visualized in the stroma. The linear structures measured approximately 40–80 μm in width. · Conclusion: Lattice corneal dystrophy presents characteristic linear images on confocal microscopy and should not be misdiagnosed as fungal hyphae in cases of corneal infection. Received: 8 July 1998 Revised version received: 6 November 1998 Accepted: 1 December 1998     

In vivo confocal microscopy of megalocornea with central mosaic dystrophy

In vivo confocal microscopy was performed on the central cornea of both eyes of a patient with megalocornea and central mosaic dystrophy. In the stroma, starting just below Bowman's membrane, polygonal, moderately reflective areas of opacification separated by diagonal hyporeflective striations were observed. The opaque areas appeared smaller in the anterior stromal layers and seemed to get larger towards the posterior stroma. The epithelium, Bowman's membrane and endothelium appeared normal. In vivo confocal microscopy is helpful in evaluating the morphological characteristics of corneal dystrophies, degenerations or developmental abnormalities of the cornea, and may prove to be helpful in understanding their pathophysiology.     

颗粒状角膜营养不良活体共焦显微镜形态学研究

目的研究颗粒状角膜营养不良角膜各层组织的共焦显微镜形态改变。方法应用Confoscan2.0共焦显微镜对13例(26眼)颗粒状角膜营养不良患者的角膜进行扫描检查,记录与分析各层角膜图像。结果所有患眼前基质细胞及16/26眼后基质细胞结构不清,排列紊乱,并可见短棒状多形性强反光;6/26眼前弹力层不规则并增厚,神经纤维密度明显下降;6/26眼角膜上皮基底细胞层可见不定型的强反光;2/26眼角膜上皮细胞边界不清,排列呈疏松的蜂窝状,并出现不透明的强反光;所有患者角膜内皮细胞形态基本正常。视力0.3以下的患眼角膜上皮细胞层、上皮基底细胞层、前弹力层、后基质层发生形态异常的比例高于0.3以上的患眼(P<0.05)。结论1.共焦显微镜可活体检查颗粒状角膜营养不良角膜组织各层结构,起到类似病理组织切片的作用。2.前基质层形态异常可能是颗粒状角膜营养不良最基本的共焦显微镜形态特征,病情越重,前基质层以外的其它层次发生形态异常的可能性越大,但内皮细胞层一般不受累。3.共焦显微镜检查对颗粒状角膜营养不良手术方式的选择具有一定的参考价值。     

In vivo confocal microscopy of patients with corneal recurrent erosion syndrome or epithelial basement membrane dystrophy

OBJECTIVE: To characterize morphologic changes in corneas of patients with recurrent erosion syndrome or epithelial basement membrane dystrophy using in vivo confocal microscopy. DESIGN: Observational case series PARTICIPANTS: Fourteen eyes of eight patients with diagnosed epithelial basement membrane dystrophy and 13 eyes of seven patients with recurrent erosion syndrome were examined. METHODS: Slit-lamp examination and in vivo confocal microscopy. The pathologic findings are presented as digitized images obtained from video tape recorded during the confocal microscopy. MAIN OUTCOME MEASURES: The morphology of corneal surface epithelial cells, basal epithelial cells, subbasal nerve plexus, Bowman's layer, stromal keratocytes, and endothelium was analyzed. RESULTS: The surface epithelium was intact in all but two eyes. One cornea (a basement membrane disorder with clinically visible dots) had multinucleate surface epithelial cells, and one eye with recurrent corneal erosions showed a freely floating surface epithelium sheet in the tear fluid. Patients in both groups showed islets of highly reflective cells with presumed intracellular deposits surrounded by normal cells in the basal epithelial cell layer. The basal epithelial cell area also showed other pathologic changes, including drop-shaped configurations, streaks, or ridges. Folding of the Bowman's layer was also observed in both groups. Anterior keratocytes showed signs of activation (highly reflective nuclei with visible processes) in some of the patients regardless of the clinical diagnosis, and in recurrent erosions even increased deposition of abnormal extracellular matrix in the anterior stroma was suspected. Posterior corneal keratocytes and endothelium appeared normal when examined. The subbasal nerve plexus showed various pathologic changes, such as short or strangely shaped nerve fiber bundles, decreased numbers of long nerve fiber bundles, only faintly visible long nerve fiber bundles (instead of the normally observed long parallel running interconnected bundles), or increased amounts of Langerhans cells, but only one patient (with recurrent erosion syndrome) lacked the subbasal nerve plexus. CONCLUSIONS: In vivo confocal microscopy of corneas with recurrent erosions or epithelial basement membrane dystrophy showed deposits in basal epithelial cells, subbasal microfolds and streaks, damaged subbasal nerves, or altered morphology of the anterior stroma. Confocal microscopy cannot replace biomicroscopy in making a specific diagnosis, but it sometimes helps the diagnosis in corneas that appear normal under a biomicroscope.     

Imaging the microstructural abnormalities of meesmann corneal dystrophy by in vivo confocal microscopy

PURPOSE: To delineate the microstructural features of Meesmann corneal dystrophy using in vivo confocal microscopy. METHOD: Three subjects with clinically diagnosed Meesmann corneal dystrophy were examined by slit-lamp biomicroscopy and slit-scanning in vivo confocal microscopy. RESULTS: On slit-lamp biomicroscopy, all subjects demonstrated large bilateral multiple epithelial cystic lesions extending to the midperiphery. On in vivo confocal microscopy, these lesions appeared as hyporeflective areas in the basal epithelial layer. The majority were circular, oval or teardrop shaped and ranged between 48 mum and 145 mum in diameter. Large elongated intraepithelial clefts were also seen. Reflective spots were visible within most of the lesions and these may represent the fibrillogranular material (termed peculiar substance) and tonofilament bundles observed in electron microscopy studies. An additional finding was the fragmented appearance of the subbasal nerve plexus. CONCLUSION: We present the first case series of Meesmann corneal dystrophy imaged by in vivo confocal microscopy and describe the associated microstructural features. Delineation of these features facilitates the use of the confocal microscope to aid diagnosis and management of corneal dystrophies.     

Microstructural assessment of rare corneal dystrophies using real-time in vivo confocal microscopy

Purpose : To analyse and describe three cases of rare corneal dystrophy and highlight their in vivo microstructural features. Methods : Subject 1 was diagnosed with a posterior stromal fleck corneal dystrophy. Two of her three children were also affected. Subjects 2 and 3 exhibited an almost identical clinical appearance on biomicroscopic examination, such that both clinically were diagnosed as having pre‐Descemet’s dystrophies. All subjects underwent in vivo confocal microscopy and approximately 300 sequential digital images were obtained and analysed for each cornea. Results : In vivo confocal microscopy of subject 1 demonstrated an abnormal appearance of numerous large ovoid particles, measuring 50–70 μm in diameter in the mid and posterior stroma as well as smaller hyperreflective dot‐like intracellular deposits, of less than 1 μm diameter. Despite the near‐identical clinical appearance, subjects 2 and 3 could be clearly differentiated by in vivo confocal microscopy. Subject 2 exhibited small, irregular, optically dense particles, mainly in the anterior stroma, whereas subject 3 possessed classical involvement of the stroma immediately adjacent to Descemet’s membrane, with numerous regular, small, hyperreflective particles. Conclusions : The ability of in vivo confocal microscopy to localize and accurately measure various elements in different corneal layers may help to resolve whether abnormalities are intra‐ or extracellular, and aid clearer differentiation of rare corneal disorders.     

Changes in corneal structure observed with confocal microscopy during Fuchs endothelial dystrophy

PURPOSE: The study aimed to in vivo evaluate corneal structure in Fuchs' dystrophy. MATERIAL AND METHODS: Forty-two eyes of 21 patients (11 women and 10 men) aged 34-80 (mean 60.8) were studied. Sixteen patients presented clinical symptoms. The cornea was examined using a Confoscan P4 scanning slit confocal microscope (Tomey). Before examination, the cornea was anesthetized with 0.5% propacaine (Alcaine, Alcon) in order to inhibit the corneopalpebral reflex. A 40x microscope objective was covered with a drop of polyarylic acid gel (Vidisic, Mann Pharma) and then it was moved horizontally close to the patient's cornea and the examination was carried out. RESULTS: In the early stage of Fuchs dystrophy, slit biomicroscopy revealed fine dark spots within the corneal endothelium, while in the advanced stage the cornea had the appearance of beaten metal. On confocal microscopy, there were diffused hyporeflective areas in the early-stage disease. The endothelial cells located beyond these areas were pleomorphic and polymegathic. In the late stage we observed diffused hyporeflective areas surrounded by hyperreflective endothelial cells, which could not be analyzed separately. Within the corneal stroma, the collagen fibers were blurred and the background illumination was increased. In the posterior part of the stroma, dark bands were seen. The epithelium contained cystic structures (blisters). The membranes of the basal cells were thickened and the background illumination was increased. CONCLUSIONS: Confocal microscopy allows to diagnose Fuchs dystrophy and visualize endothelial cells within the swollen cornea.     

Confocal microscopy in a case of crystalline keratopathy in a patient with smouldering multiple myeloma

We report the clinical and confocal microscopic findings of the cornea in a patient with smouldering multiple myeloma (SMM) using in vivo scanning laser confocal microscopy. A 72-year-old female underwent a complete ophthalmological examination including slit-lamp biomicroscopy with digital photography, HRT II laser scanning in vivo confocal microscopy and haematological laboratory assessment. Corneal biomicroscopy revealed the presence of bilateral diffuse microgranular tiny grey opacities. In vivo confocal microscopy showed randomly oriented hyper-reflective needle-shaped crystals throughout all levels of the stroma, sparing epithelium and endothelium. In vivo confocal microscopy was very helpful in the differential diagnosis by allowing the nature of the corneal deposits to be established, revealing the typical aspect of the crystals, and excluding granular dystrophy, leading to a suspected diagnosis of SMM. Crystalline corneal deposits may easily be confused as crumb-like opacities typical of granular dystrophy on slit-lamp examination even by experienced ophthalmologists.     

In vivo confocal microscopy of fleck dystrophy

PURPOSE: To use in vivo confocal microscopy to evaluate corneas with fleck dystrophy. METHODS: Both eyes of three patients with corneal fleck dystrophy were examined with a scanning slit confocal microscope. Corneal epithelium, stroma, and endothelium were evaluated, as well as the basal epithelial and stromal nerves. RESULTS: The epithelium did not show any anomalies, but the basal nerves showed hyperreflective inclusions. Throughout the entire stroma, hyperreflective dots of various shapes were seen. These consisted mostly of spherical matter with a diameter of 3-5 microm and were sometimes enclosed in cyst-like structures. The majority of the stromal cells and stromal nerves appeared normal. The endothelial cell layer was unaffected. CONCLUSION: In vivo confocal microscopy demonstrates previously unreported inclusions in the basal nerves of fleck dystrophy corneas. In addition to this new finding, the study confirms earlier histopathologic reports, demonstrating accumulation of pathologic material in the stromal cells.     

Long-term microstructural changes following epikeratophakia: in vivo confocal microscopy study

The unilateral epikeratophakic eye of a 20-year-old woman with a history of congenital cataracts was examined using laser scanning in vivo confocal microscopy 17 years after transplantation. In vivo confocal microscopy demonstrated a reduced keratocyte density in the grafted lenticule and the host stroma, with unusual elongated and tortuous hyperreflective branching structures in the anterior stroma of the host cornea. The sub-basal nerve plexus was present in the lenticule, although with a reduced nerve density. The appearance of the host endothelium was similar to that observed in Fuchs endothelial dystrophy. Dramatic microstructural changes were observed in almost all layers of the cornea 17 years after epikeratophakia. Although no longer performed as routine practice, in vivo confocal microscopy examination of epikeratophakia has provided fascinating insight into the potential corneal adaptations at a cellular level.     

In vivo confocal microscopy in the patients with cornea farinata

PURPOSE: To report in vivo corneal confocal microscopic findings of patients with cornea farinata. PATIENTS AND METHODS: Two unrelated patients, a 47-year-old man and a 77-year-old woman, with cornea farinata were studied. Examination with a confocal microscope was performed in addition to routine slit-lamp biomicroscopy. RESULTS: In both cases, slit-lamp biomicroscopy showed numerous small, faint opacities in the deep stroma in both eyes. Using confocal microscopy, highly reflective small particles were observed in the cytoplasm of keratocytes in the deep stroma adjacent to the corneal endothelial layer. No abnormalities could be detected in the epithelial layer, in the mid-stromal layer, at the level of Descemet's membrane, and in the endothelial layer. CONCLUSIONS: In vivo corneal confocal microscopy is useful for observing stromal abnormalities in cornea farinata. Further investigation of posterior stromal opacities using confocal microscopy may be useful to understand and differentiate various corneal conditions involving primarily deep stromal layers.     

Two mutations in the TGFBI (BIGH3) gene associated with lattice corneal dystrophy in an extensively studied family

PURPOSE: To determine the genetic basis for lattice corneal dystrophy (LCD) in an extensively studied family. METHODS: Ten affected family members were examined clinically, and three individuals were studied with in vivo confocal microscopy and optical coherence tomography (OCT). Corneal tissues from eight affected family members were examined histopathologically. The status of the transforming growth factor beta-induced gene (TGFBI) gene was determined in each consenting family member (six affected, seven nonaffected) by amplifying, sequencing, and analyzing exons 4 and 12 of TGFBI for mutations. All exons from the entire coding region of TGFBI of one affected person were analyzed for mutations. RESULTS: Slit lamp biomicroscopy disclosed the clinical features of LCD in both eyes of affected individuals. In vivo confocal microscopy confirmed the presence of deposits as bright lesions within the corneal stroma. OCT revealed increased reflectivity within the corneal stroma. The corneal stroma in persons undergoing penetrating keratoplasty contained amyloid. Affected members of the family were found to have two heterozygous single-nucleotide mutations in exon 12 of the TGFBI gene (C1637A and C1652A) leading to predicted amino acid substitutions in the encoded TGFbeta-induced protein (A546D and P551Q). Mutations were not detected in exon 4. In addition, an inconsequential single-nucleotide polymorphism T1620C (F540F) was found in some affected and nonaffected family members. CONCLUSIONS: Two mutations in the TGFBI gene (A546D and P551Q) cosegregated with LCD in an extensively studied family that lacked the R124C mutation that frequently accompanies this form of corneal amyloidosis.     

Report of a new family with dominant congenital heredity stromal dystrophy of the cornea.

PURPOSE: To report a new family with the rare form of congenital and hereditary stromal dystrophy of the cornea. METHODS: A mother and son, showing a bilateral congenital clouding of the cornea, were studied clinically and by biomicroscopy. After corneal transplantation, light microscopy and electron microscopy were performed. RESULTS: The stroma of the cornea was bilaterally and symmetrically thickened with diffuse and homogeneous small opacities. The opacities were present at birth and slowly progressive. Visual acuity was reduced to 2/10. Electron microscopy of the excised corneas showed a thickened stroma owing to cleaving of the lamellae by alternating layers of small-diameter collagen fibrils arranged in a random fashion. The epithelium, Bowman's membrane, the endothelium, and Descemet's membrane were normal. CONCLUSIONS: This family presents with a congenital stromal dystrophy of the cornea not linked to endothelial defects and thus differs from the more common form of congenital hereditary corneal endothelial dystrophy.     

In vivo confocal microscopy of human cornea covered with human amniotic membrane

Purpose  Amniotic membrane transplantation has been widely performed to reconstruct the surface of the eye and treat chemical burns or epithelial defects. However, we have difficulty observing the cornea through the opaque transplanted amniotic membrane by slit-lamp biomicroscopy. We investigated the use of confocal microscopy for observation of human corneas covered with amniotic membrane. Methods  Human amniotic membrane was placed onto the normal corneas of five volunteers aged 22–24 years. Then, all layers of the covered corneas were observed by in vivo confocal microscopy. Results  Confocal microscopy displayed the epithelium, basement membrane, and stroma of the amniotic membrane. It also displayed the corneal epithelium. Furthermore, corneal stromal keratocytes and the corneal endothelium were clearly observed through the amniotic membrane by confocal microscopy. Conclusions  We demonstrated that in vivo confocal microscopy enabled us to observe all layers of corneas covered with amniotic membrane in normal human eyes. Our findings suggest that confocal microscopy may have advantages for clinical examination of the ocular surface, including all layers of the cornea.     

In vivo confocal microscopy of pre-endothelial deposits

BACKGROUND: Deposits in various layers of the cornea might result from long-term medical therapy, photorefractive surgery, and longterm use of contact lenses or corneal dystrophies. METHODS: A 46-year-old woman was referred to our department with the suspected diagnosis of posterior polymorphous dystrophy. Slit-lamp biomicroscopy revealed bilateral small-sized deposits in the posterior part of the cornea. In vivo confocal microscopy was performed to evaluate these deposits in detail. RESULTS: In vivo confocal microscopy of the cornea identified hyperreflec-tive "dot-like" structures in the deep stromal layer and anterior to the endothelial cell layer. The morphology and number of keratocytes of the posterior stroma and of endothelial cells appeared normal. CONCLUSIONS: In vivo confocal microscopy is a very useful tool to analyze and visualize pre-endothelial deposits. Because there is no family history of corneal disease, the exact origin of the pre-endothelial deposits in our case remains unclear.     

Biomicroscopia confocal en 4 pacientes con distrofia corneal policromática

Introduction

Polychromatic corneal dystrophy is an unusual pre-descemet dystrophy, about which there are very few publications. The findings are presented in a case series of four patients with polychromatic corneal dystrophy, using a slit lamp, specular biomicroscopy, and confocal microcospy.

First Identification of a Triple Corneal Dystrophy Association: Keratoconus,Epithelial Basement Membrane Corneal Dystrophy and Fuchs’ Endothelial Corneal Dystrophy

Purpose

To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs’ endothelial corneal dystrophy (FECD).

Methods

A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing.

Results

Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman''s layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1.

Conclusion

This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.Key words: Keratoconus, Fuchs’ endothelial corneal dystrophy, Epithelial basement membrane dystrophy, Cogan dystrophy, Confocal microscopy, ZEB1     

In vivo confocal microscopy in a patient with keratopigmentation (corneal tattooing)

PURPOSE: To report in vivo corneal confocal microscopic findings in a patient with keratopigmentation (corneal tattooing). PATIENTS AND METHODS: A 64-year-old woman who received keratopigmentation for bilateral corneal opacity 53 years ago was examined by confocal microscope. RESULTS: By confocal microscopy, scattered highly reflective particles in a geographic pattern were observed in the superficial stroma near Bowman layer. In addition, clusters of highly reflective granules were in the mid- to superficial stroma. CONCLUSIONS: In vivo confocal microscopy can be used for monitoring keratopigmentation. The findings may serve to distinguish keratopigmentations from other pigmented corneal lesions.