In vivo confocal microscopic characteristics of iridocorneal endothelial syndrome

PURPOSE: To analyse five cases of iridocorneal endothelial (ICE) syndrome and describe the microstructural characteristics observed by in vivo confocal microscopy. METHODS: All five subjects presented with clinical characteristics suggestive of ICE syndrome and were examined clinically by Orbscan II pachymetry and by in vivo confocal microscopy. At least 600 sequential digital confocal images throughout the z-axis were analysed qualitatively and quantitatively for each cornea. RESULTS: Clinically, all subjects presented with: minimal to moderate corneal oedema, focal to diffuse 'beaten metal' appearance of the corneal endothelium, and varying degrees of iris atrophy. Three subjects had a history of elevated intraocular pressure. In vivo confocal microscopy highlighted two main patterns of endothelial change: small cells (mean maximal diameter of 13.6 +/- 1.5 micro m), with indistinct borders and very bright and prominent, uniform nuclei (two subjects) and larger, epithelioid-like cells (mean maximal diameter of 26.6 +/- 5.5 micro m), with irregular borders and non-homogenous, diversely shaped nuclei (three subjects). Different degrees of alteration of stromal structure, very prominent corneal nerves and unusual syncytia of keratocytes were also observed. Significant oedema of the basal epithelium with increased reflectivity of the intercellular spaces was prominent in all cases. CONCLUSIONS: Although ICE syndrome is considered to be primarily an endothelial disease, in vivo confocal microscopy demonstrated structural alterations throughout the entire cornea even in clinically mild cases. The ability of in vivo confocal microscopy to localize and accurately measure various elements in different corneal layers will assist differentiation of various presentations of ICE syndrome as this technique becomes increasingly available in clinical practice.     

In vivo confocal microscopy of climatic droplet keratopathy

We describe the corneal microstructural changes in a patient with spheroidal degeneration using in vivo confocal microscopy. Multiple hypo‐ and hyper‐reflective spherical lesions were observed in the anterior corneal stroma and Bowman's layer ranging from 45 to 220 μm in size. The corneal epithelium, posterior stroma and endothelium were otherwise unaffected. In vivo confocal microscopy demonstrates good correlation with excised histological samples in climatic droplet keratopathy. It provides a non‐invasive technique to examine the living cornea for degenerative disease and acts as a bridge between clinical and laboratory observations.     

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.     

圆锥角膜行去上皮角膜胶原交联术后角膜微结构的变化

目的：采用共焦显微镜观察进展期圆锥角膜行去上皮角膜胶原交联术后角膜微结构的变化。

方法：选取2016-02/2017-02于我院行上皮角膜胶原交联术治疗的进展期圆锥角膜患者11例15眼,分别于手术前后行共焦显微镜检查,观察角膜微结构变化。

结果：术后早期角膜上皮下神经纤维显著减少或消失; 角膜前基质呈蜂窝状,几乎无典型的角膜基质细胞,术后3mo基质细胞开始出现,术后12mo基质细胞数量几乎恢复到术前水平,但角膜上皮下神经仍稀疏,未达到术前水平; 术后后部角膜基质细胞和内皮细胞大小及形态未受影响。

结论：角膜胶原交联术后角膜微结构发生变化最明显的是上皮下神经纤维和前基质细胞,但随着随诊时间的延长,这种变化呈逐渐减弱趋势。     

Conjunctival and corneal findings in bleb‐associated endophthalmitis: an in vivo confocal microscopy study

Purpose: To report the conjunctival and corneal findings in delayed onset glaucoma filtering bleb‐associated endophthalmitis (BAE), by using in vivo confocal microscopy (IVCM). Methods: This was an observational case series. Four eyes of four glaucomatous patients who previously underwent mytomicin C augmented filtering surgery and affected with delayed onset BAE, underwent IVCM of conjunctival bleb and cornea at diagnosis, after 2 and 8 weeks of therapy. The inflammatory status of the conjunctival epithelium and sub‐epithelium was microscopically investigated. Corneal epithelial cells, stromal and endothelial morphology were also evaluated. A group of eight patients with functioning conjunctival filtering bleb was used as control. Results: At diagnosis, a diffuse inflammatory cell infiltration within the conjunctival epithelium presenting evident microcysts was found; conversely, there were no such alterations in the sub‐epithelium. An evident stromal oedema, keratocytes activation and diffuse endothelial inflammatory precipitates were the major corneal hallmarks. After 2 weeks of therapy, besides a remarkable improvement of epithelial inflammation and an evident reduction in endothelial precipitates, dendritic cells appeared within conjunctival sub‐epithelium and corneal epithelium showed aspects of cellular disruption. After 8 weeks, the conjunctival and corneal features consistently improved, except for the endothelium which still presented high‐reflective residual precipitates. Conclusions: In vivo confocal microscopy proved valuable in the analysis of conjunctival bleb and cornea in patients affected with delayed onset BAE, permitting an evaluation of the course of the disease, the response to therapy and the modulation of dose regimen.     

Confocal microscopy in the iridocorneal endothelial syndrome

AIMS: To report the appearances of iridocorneal endothelial (ICE) syndrome from real time, white light confocal microscopy. METHODS: Three consecutive patients, each with ICE syndrome, were examined prospectively. Corneal specular and confocal microscopic examinations were performed in all three patients. In the first patient, a penetrating keratoplasty was performed and the cornea was examined by light and scanning electron microscopy. No surgery was performed in the remaining two patients. RESULTS: In the first patient corneal oedema prevented endothelial specular microscopy. Confocal microscopy performed before penetrating keratoplasty successfully revealed abnormal epithelial-like endothelial cells. Histological examinations of the cornea following penetrating keratoplasty revealed the presence of multilayered endothelial cells with epithelial features (microvilli). In the remaining two patients, specular microscopy showed the presence of ICE cells with typical dark/light reversal. Confocal microscopy demonstrated groups of endothelial cells with epitheloid appearances. In all three patients, the contralateral endothelial appearance was normal by specular and confocal microscopy, except for moderate endothelial polymegathism in one patient. Epithelial-like endothelial cells were characterised by prominent nuclei on confocal microscopy. CONCLUSIONS: The application of confocal microscopy indicates that the ICE syndrome is characterised by epitheloid changes in the endothelium. Confocal microscopy may be used to diagnose the ICE syndrome by demonstrating epithelial-like endothelial cells with hyperreflective nuclei. This technique is especially of value in cases of corneal oedema, since specular microscopy may fail to image the endothelium in such cases.     

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 and ex vivo in situ confocal analysis of a rat model demonstrating transient 'epithelialization of the endothelium'

The purpose of this study was to identify the in vivo microstructural characteristics of an animal model of 'epithelialization of the endothelium' that are similar in appearance to the in vivo confocal microscopical appearance of corneal endothelium previously thought to be diagnostic of irido-corneal endothelial syndrome, and correlate these observations with ex vivo in situ confocal microscopical analysis. A rat model (n = 8 eyes)of transient 'epithelialization of the endothelium' resulting from superficial corneal trauma, was developed and analysed using in vivo confocal microscopy. One animal was killed at 48 hand the cornea was immuno-labelled and analysed, using ex vivo in situ confocal digital image reconstruction. Reversible 'epithelialization of the endothelium' was observed by in vivo confocal microscopy 48 h after superficial corneal trauma in all eight eyes. Ex vivo in situ analysis failed to demonstrate immunohistological characteristics of epithelialization. In vivo confocal microscopy is based on optical principles, and as a result various structural alterations may present with apparently identical characteristics that should be interpreted cautiously, on the basis of the presented clinicopathological observations.     

Confocal microscopy in cornea guttata and Fuchs'' endothelial dystrophy

AIMS: To report the appearances of cornea guttata and Fuchs' endothelial dystrophy from white light confocal microscopy. METHODS: Seven eyes of four consecutive patients with cornea guttata were prospectively examined. Of the seven eyes, three also had corneal oedema (Fuchs' dystrophy). In vivo white light tandem scanning confocal microscopy was performed in all eyes. Results were compared with non-contact specular microscopy. RESULTS: Specular microscopy was precluded by corneal oedema in one eye. In the remaining six eyes, it demonstrated typical changes including pleomorphism, polymegathism, and the presence of guttae appearing as dark bodies, some with a central bright reflex. In all seven eyes, confocal microscopy revealed the presence of round hyporeflective images with an occasional central highlight at the level of the endothelium. Changes in cell morphology and size were readily appreciated. CONCLUSION: By comparison with specular microscopy, the hyporeflective images with an occasional central highlight seen on confocal microscopy are consistent with the presence of guttae. Confocal microscopy may confirm the diagnosis of cornea guttata and Fuchs' endothelial dystrophy by demonstrating the presence of guttae. This technique is especially valuable in cases of corneal oedema, where specular microscopy may fail to visualise the endothelium. However, specular microscopy should remain the method of choice to evaluate the endothelium, principally because it is easier to use.     

In vivo confocal laser-scanning microscopy to characterize wound repair in rabbit corneas after collagen cross-linking

Background: Collagen cross‐linking using the photosensitizer riboflavin combined with ultraviolet A light was developed to stiffen the cornea by increasing its mechanical and biochemical stability. Investigation of post‐treatment events, such as wound healing, is important to evaluate possible risks and to optimize treatment protocols. This in vivo confocal laser‐scanning microscopy study in rabbits was conducted to provide a quantitative and qualitative analysis of corneal wound repair over 16 weeks following collagen cross‐linking. Methods: Six New Zealand White rabbits underwent riboflavin/ultraviolet A cross‐linking. In vivo confocal laser‐scanning microscopy using a Heidelberg Retina Tomograph equipped with a Rostock Cornea Module was performed preoperatively and at 2, 4, 8, 12 and 16 weeks postoperatively. Results: From 2 weeks onwards the epithelium demonstrated no abnormalities. Evidence of inflammation was visualized in the intermediate, basal cells and Bowman's membrane. Nerve fibre regeneration was first noted at 12 weeks. Keratocyte activation and hyperreflective extracellular matrix were observed consistently, but by 16 weeks keratocyte activation was diminished, and extracellular matrix resumed normal reflectivity. Cell density in the posterior stroma and endothelium regained preoperative values by 4 weeks, although anterior stroma keratocyte cell density was still reduced by about 10% at 16 weeks. Conclusions: Complete qualitative and quantitative characterization of corneal wound repair was achieved by in vivo confocal laser‐scanning microscopy over 16 weeks following collagen cross‐linking in rabbits. In terms of assessing the ever‐increasing range of cross‐linking protocols, in vivo confocal laser‐scanning microscopy may contribute to minimizing the number of experimental animals, because multiple examinations of the same cases are possible over time.     

In vivo corneal confocal microscopic findings of palisades of Vogt and its underlying limbal stroma

PURPOSE: To demonstrate the corneal confocal microscopic findings of limbal palisades of Vogt and its underlying limbal stroma. METHODS: Two unrelated healthy subjects (a 56-year-old man and a 40-year-old man) with prominent palisades of Vogt were enrolled in this study. A detailed examination with confocal microscopy was performed in addition to a routine slit-lamp biomicroscopy. Cell sizes of epithelial basal layers of both the central and limbal (beneath the palisades of Vogt) were measured and statistically analyzed. RESULTS: In both subjects, confocal microscopy in the region of the palisades of Vogt revealed normal appearance of corneal superficial layers. However, in some images, undulant basal epithelial layer was observed. In the superficial stromal layer adjacent to the corneal epithelium, we noted corneal nerves that seemed to terminate at the epithelial basal layers. The mid-stromal layers showed a highly reflective spatter-like pattern as well as numerous dark striae in a branching pattern. The corneal endothelial layer seemed normal. The average cell size of epithelial basal cells beneath the palisades of Vogt was significantly smaller than those of the central cornea (P = 0.015 and 0.005 in cases 1 and 2, respectively). CONCLUSIONS: In vivo corneal confocal microscopy is useful in observing limbal stromal microstructures. Further investigations of pathologic corneal limbus may be useful in elucidating the mechanisms contributing to corneal limbal epithelial stem cell deficiency.     

Morphological and functional correlations in riboflavin UV A corneal collagen cross‐linking for keratoconus

Purpose: To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle‐corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross‐linking (CXL) for the stabilization of progressive keratoconus. Methods: Forty‐four eyes with progressive keratoconus were enrolled in the Siena Eye Cross Study (prospective nonrandomized phase II open trial). All eyes underwent Riboflavin UV A CXL. Preoperative and postoperative evaluation comprised: UCVA, BSCVA, optical pachymetry (Visante OCT, Zeiss, Germany), corneal topography (CSO, Florence, Italy) and tomography (Orbscan IIz; B&L, Rochester, NY, USA) and in vivo confocal microscopy (Heidelberg Retina Tomograph II; Rostock, Heidelberg Gmbh, Germany). Examinations were performed preoperatively 6 months and one day before treatment and at 1, 3, 6 and 12 months of follow‐up. Results: In vivo corneal confocal microscopy showed time‐dependent postoperative epithelial and stromal modifications after cross‐linking. Epithelial thinning associated with stromal oedema and keratocytes apoptosis explained initial tendency towards slightly reduced VA and more glare one month postoperatively in 70% of eyes. Furthermore, a statistically not significant early worsening of topographic mean K values was observed. Orbscan II analysis significantly underestimated pachymetric values after treatment. Pachymetric underestimation was rectified by high‐resolution optical pachymetry provided by the Visante OCT system. After the third post‐CXL month, epithelial thickening, disappearance of oedema and new collagen compaction recorded by in vivo corneal confocal microscopy explained the improvements in visual performance during the follow‐up. Changes in stromal reflectivity and collagen compaction observed by in vivo confocal microscopy were associated with corneal flattening and reduction in anterior elevation values recorded by differential topographic analysis. Conclusion: Corneal structural changes assessed by in vivo corneal confocal microscopy demonstrated significant correlations with visual function (UCVA and BSCVA) and morphological (corneal topography, pachymetry, elevation analysis) findings recorded after riboflavin‐UV A‐induced CXL.     

PROGRESSIVE CORNEAL ENDOTHELIAL CELL CHANGES IN ANTERIOR SEGMENT DISEASE

We have demonstrated marked changes in the corneal endothelium in some groups of patients with ocular anterior segment disease including chronic cyclitis, both heterochromic an! classical pseudoexfoliation of the lens capsule, and anterior segment pigment dispersal syndrome. The most striking changes occurred in heterchromic cyclitis with reduced endothelial cell counts (p>0.01) and altered cellular morphology. In almost all eyes with cyclitis endothellal belbs were seen. In eyes with unilateral pseudoexfoliation of the lens capsule there was a lower endothelial cell count with pleomorphisrn and polymegathism, the changes being somewhat more marked with raised introcular pressure (p>0.07). In anterior segment pigment dispersal syndrome there was an even smaller reduction in count (p>0.05)with mild changes in morphology. Factors producing endothelial cell changes included hypoperfusion of the iris with microneovascularisation of the iris stroma, intercellular bleb formation with oedema of the corneal endothelium. and raised intraocular pressure. A normal iris circulation is important to the integrity of the corneal endothelium.     

In-vivo confocal microscopy of iridocorneal endothelial syndrome

Background: We carried out a study by in-vivo confocal microscopy to investigate the appearance of iridocorneal endothelial (ICE) syndrome, and discuss its diagnostic potential. Methods: Twelve patients, each with unilateral ICE syndrome, had both their eyes examined by in-vivo confocal microscopy. The images were recorded and analyzed by the use of proprietary software. Endothelium density, average endothelial area, coefficient of variation of cell size, percentage of hexagonal cells, and nerve fiber diameter were measured in both the anterior and posterior stroma. Corneal thickness was also measured for both eyes. A non-parametric test was used to compare differences between the affected eye and the contralateral healthy one. Results: In-vivo confocal microscopy highlighted two main patterns of abnormal “epithelioid-like” endothelium, both characterized by marked hyperreflective nuclei and loss of regularity in cellular size and shape. The first pattern was relatively regular cell size and shape, conserving a pattern similar to that of normal endothelial cells. However, the cells lost normal hexagonality and presented prominent uniform “cobblestone-like” nuclei occupying the central area of the cells. The second type was more irregular in cellular size and shape, with hyperreflective diversely shaped nuclei adjacent to the boundaries of the cells. Cells with two nuclei could be found in both types. Compared with the contralateral eye, the stromal nerve fibers in affected eyes were unusually thicker and distorted. Nerve diameters in the anterior stroma of affected eyes and contralateral eyes were 5.7 ± 0.5 μm and 3.2 ± 0.2 μm, respectively; those in the posterior stroma were 10.8 ± 0.3 μm and 6.6 ± 0.4 μm, respectively (both P < 0.001). Conclusions: Application of confocal microscopy indicates that ICE syndrome is characterized by pleomorphic epithelioid-like endothelial cells with hyperreflective nuclei. The technique has great potential in diagnosing ICE syndrome, especially in cases with corneal edema.     

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。     

后部多形性角膜营养不良49例共聚焦显微镜影像学观察

目的:探讨49例后部多形性角膜营养不良(PPCD)患者在共聚焦显微镜(IVCM)下的影像学特征。方法:回顾性病例研究。收集我院2013-01/2021-01诊断为PPCD患者49例86眼,包括男32例,女17例,平均年龄42.5±22.9岁。所有患者均进行IVCM检查,分析角膜内皮细胞密度及不同类型病变的镜下特点。结果:所有患者病灶区内皮细胞数量均较外周细胞数量低。IVCM下病变呈1型囊泡型的有44眼(51%),表现为角膜内皮层的圆形或不规则弹坑样病灶,单个或多个出现;2型条带型16眼(19%),表现为边缘弧形凸起,部分可见似赘疣样影像散在或条索状分布;3型弥漫型26眼(30%),表现为内皮细胞大面积缺失,大部分区域内皮成像不清,呈匍匐样、条索样延展的凸起,成像较清晰处部分同条带型病灶。观察病例中有2例患者随访4～5a, IVCM下病灶均较前有变化,包括中央角膜内皮数量的减少和上皮层铁质沉着等。结论:IVCM能够显示PPCD患者各期内皮细胞和Descemet膜水平的特征性显微结构改变,通过观察其影像学特点可以为疾病提供有效的诊断价值。     

In vivo confocal microstructural analysis and surgical management of Brown-Mclean syndrome associated with spontaneous crystalline lens luxation

We report 3 members of an extended family who presented with bilateral peripheral corneal edema consistent with Brown-McLean syndrome. On clinical examination, all eyes demonstrated normal central corneas and marked peripheral edema. In vivo confocal microscopy of the peripheral cornea highlighted similar observations in the 6 eyes including endothelial pigmentation, masked stromal structure due to edema, prominent nerves, and localized basal epithelial edema. In the central cornea, in vivo confocal microscopic observations highlighted large cellular structures with prominent nuclei in groups consisting of several cells of similar appearance. In vivo confocal microscopy may enhance the diagnosis of Brown-McLean syndrome and may be used for dynamic evaluation and postoperative follow-up of the structural corneal changes.     

Imaging posterior polymorphous corneal dystrophy by in vivo confocal microscopy

To identify features of posterior polymorphous dystrophy (PPMD) by in vivo confocal microscopy, the corneas of a female patient with PPMD were examined using slit‐lamp biomicroscopy and slit‐scanning in vivo confocal microscopy. Characteristic endothelial vesicular and band lesions were seen clinically and easily identified using in vivo confocal microscopy. However, endothelial pleomorphism, an increased density and reflectance of posterior stromal keratocytes, and prominence of corneal nerves were also delineated. In vivo confocal microscopy enhances clinicopathological diagnosis and follow up of corneal dystrophies with subtle clinical presentations, such as PPMD.     

In vivo confocal microscopy of corneal grafts shortly after penetrating keratoplasty

PURPOSE: To describe the microstructural status of corneal grafts shortly after penetrating keratoplasty (PK) and to evaluate the efficacy and safety of confocal microscopy in examining corneal grafts at that time. METHODS: A confocal microscope with a 40 x front lens was used to examine corneal grafts in 32 patients (32 eyes) 4 days after PK. Images were analyzed, and endothelial cell density counts were compared with presurgical, eye bank values determined by specular microscopy. RESULTS: Microstructural alterations of the graft included epithelial and stromal edema, epithelial degeneration in both superficial and basal cell layers, dark stromal striae, activated keratocytes, and needle-like structures in the stroma. Descemet membrane folds were visible in 31 of 32 grafts; in 1 graft, the dense stromal edema did not allow imaging of posterior layers. Stromal nerve fibers were imaged in 28 grafts (88%). Endothelial cell density ranged from 1666 to 2548 cells/mm2 (mean+/-SD, 2125+/-283 cells/mm2); perioperative endothelial cell density loss varied from 0% to 29% (mean, 12%). No adverse reactions or signs of worsening of clinical condition were observed after the examination. CONCLUSIONS: White light scanning slit confocal microscopy permits imaging of a graft's microstructure (including epithelium and stromal layers), as well as calculation of endothelium cell density, as soon as 4 days after PK. The most frequently observed morphologic alterations of corneal grafts shortly after PK include epithelial and stromal edema, epithelial degeneration, stromal striae, and Descemet membrane folds. Stromal nerves can still be seen in the graft 4 days after PK.     

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