Iridocorneal Endothelial Syndrome: Case Report of Essential Progressive Iris Atrophy.

Background: Iridocorneal endothelial (ICE) syndrome is a group of ophthalmic disorders, first reported by Eagle and Yanoff in 1979, a disease characterized by abnormalities of the iris and the corneal endothelium, and mainly occurs unilaterally in young and middle-aged women, with no family history. ICE syndrome comprises a spectrum of three clinical variants: Progressive essential iris atrophy (corectopia, iris atrophy or iris hole), Chandler syndrome (corneal oedema with mild to absent iris change), and Cogan - Reese syndrome (nodular pigmented lesion of the iris). Objective: We are presenting this case because of its rarity, diagnostic intricacy and therapeutic challenge. Case report: We report in this study a case of Essential Progressive Iris Atrophy, an Iridocorneal Endothelial Syndrome variant in a 40 years old patient, female, complaining about the shape of the pupil in the left eye, as well as photophobia in the same side.In the first evaluation, we observed visual acuity of 1.0 in both eyes.Intraocular pressure was 14 mm Hg in the right eye and 12 mm Hg in the left eye. On the biomicroscope, we had a proper right eye finding, on the left eye Iris atrophy with deformity in the direction from 12 to 6 hours. We performed gonioscopy, an ultra sound (UBM), spectral microscopy, pachymetry, OCT and Octopus perimetry. Conclusion: We confirmed the diagnosis of essential iris atrophy based on the clinical findings, and in abnormalities in complementary exams. Nowadays, the patient is being followed in the Ophthalmology department at JZU Brcko District Bosnia and Herzegovina.

Diseases of the corneal endothelium.

The corneal endothelial monolayer and associated Descemet's membrane (DM) complex is a unique structure that plays an essential role in corneal function. Endothelial cells are neural crest derived cells that rest on a special extracellular matrix and play a major role in maintaining stromal hydration within a narrow physiologic range necessary for clear vision. A number of diseases affect the endothelial cells and DM complex and can impair corneal function and vision. This review addresses different human corneal endothelial diseases characterized by loss of endothelial function including: Fuchs endothelial corneal dystrophy (FECD), posterior polymorphous corneal dystrophy (PPCD), congenital hereditary endothelial dystrophy (CHED), bullous keratopathy, iridocorneal endothelial (ICE) syndrome, post-traumatic fibrous downgrowth, glaucoma and diabetes mellitus.

Iridocorneal endothelial syndrome in a patient with keratoconus - a case report.

BACKGROUND: To describe a case of a rare association of bilateral keratoconus and unilateral essential iris atrophy and to conduct a literature review of the current strategies of treatment of the corneal disease and glaucoma in patients with Iridocorneal Endothelial Syndrome (ICE). CASE PRESENTATION: We report a rare association of bilateral keratoconus and unilateral essential iris atrophy in a 38-year-old man. Diagnosis of bilateral keratoconus was confirmed by corneal topography. Slit-lamp examination showed extensive iris atrophy with corectopia and policoria in one eye. Corneal specular microscopy revealed an abnormal endothelium morphology in the same eye with extensive peripheral anterior synechiae and closure of the drainage angle at gonioscopy. Intraocular pressure was 26 mmHg, despite maximal topical therapy. Optic disc examination showed severe glaucomatous cupping. Surgery by glaucoma drainage device implantation was performed. CONCLUSION: Essential iris atrophy is a rare clinical variant of ICE syndrome characterized by profound anatomical alterations of the anterior segment associated with corneal edema and secondary glaucoma. In these patients, selective keratoplasties have replaced penetrating keratoplasty to treat corneal decompensation and glaucoma drainage devices are preferred to conventional trabeculectomy for the treatment of secondary glaucoma.

The Molecular Basis of Fuchs' Endothelial Corneal Dystrophy.

Fuchs' endothelial corneal dystrophy (FECD) is a common disease resulting from corneal endothelial cell dysfunction. It is inherited in an autosomal dominant fashion with incomplete penetrance, and with a female bias. Approximately half of cases occur sporadically, and the remainder are familial. Early and late-onset forms of the disease exist. A review of the literature has revealed more than 15 genes harbouring mutations and/or single nucleotide polymorphisms associated with FECD. The proteins encoded by these genes cover a wide range of endothelial function, including transcription regulation, DNA repair, mitochondrial DNA mutations, targeting of proteins to the cell membrane, deglutamylation of proteins, extracellular matrix secretion, formation of cell-cell and cell-extracellular matrix junctions, water pump, and apoptosis. These genetic variations will form the platform for the further understanding of the pathological basis of the disease, and the development of targeted treatments. This review aims to summarise known genetic variations associated with FECD, discuss any known molecular effects of the variations, how these provide opportunities for targeted therapies, and what therapies are currently in development.

Mitochondrial A3243G mutation results in corneal endothelial polymegathism.

PURPOSE: The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities. METHODS: We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing. RESULTS: Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm2, the average endothelial cell size was 442 ± 103 µm2 and the average central corneal thickness (CCT) was 551 ± 33 µm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity. CONCLUSIONS: In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.

Clinical outcome of Descemet stripping automated endothelial keratoplasty in 18 cases with iridocorneal endothelial syndrome.

PurposeTo evaluate the clinical outcome of Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with iridocorneal endothelial (ICE) syndrome.Patients and methodsA retrospective case series study was conducted. Eighteen consecutive Chinese patients with 20 DSAEK grafts were enrolled. Participants were evaluated by anterior segment optical coherence tomography and confocal microscopy. Postoperative complications, graft survival, endothelial cell counts, corneal thickness, and anterior chamber depth were analysed. A Log-rank test in a Kaplan-Meier analysis and a Cox proportional hazard regression were used to analyse potential risk factors of graft failure.ResultsThe mean follow-up duration was 19.0±8.6 months. The donors' endothelial cell density (ECD) (cells/mm2) values at 1, 3, 6, 12, 18, and 24 months were 3342.2±287.0, 1897.6±745.4, 1793.6±755.7, 1618.1±604.3, 1421.9±650.8, 1265.1±844.1, and 1148.2±1217.8, respectively. Eleven of the 20 grafts exhibited secondary graft failure, with a mean estimated graft survival of 23.4 months. Immediate postoperative complications (air bubble ventilation for elevated intraocular pressure or rebubbling for graft detachment) were more common in eyes exhibiting graft failure (P=0.040). Postkeratoplasty glaucoma surgery emerged as a risk factor of graft failure, with a hazard ratio of 5.174. Eyes with a poor prognosis showed statistically greater central corneal thickness at 1 month, greater graft thickness at 3 months, and a shallower anterior chamber at 6 and 12 months.ConclusionsThe long-term outcome of DSAEK in eyes with ICE syndrome is relatively poor. Immediate postoperative complications, postkeratoplasty glaucoma surgery, thicker corneal parameters, and a shallow anterior chamber were all associated with graft failure.

[Diagnostic methods in the clinical evaluation of iridocorneal endothelial syndrome]. / Diagnostische Methoden bei der klinischen Untersuchung des iridokornealen endothelialen Syndroms.

BACKGROUND: This article presents a patient with iridocorneal endothelial (ICE) syndome. CASE REPORT: A 35-year-old man presented with unilateral slightly decreased visual acuity. Examination by slit-lamp biomicroscopy of the affected eye revealed alterations to the corneal endothelial layer, which had a silver-grey and hammered appearance. Corectopia with the pupil drawn towards an area with peripheral anterior synechiae could be gonioscopically detected. In vivo confocal microscopy of the cornea revealed alterations of the corneal endothelial layers of the affected eye, namely epithelization of the endothelium with pleomorphic epithelioid cells of irregular size and shape, indistinct borders and hyperreflective nuclei. CONCLUSION: In vivo confocal microscopy of the cornea is a sensitive diagnostic method for the rapid and early diagnosis of ICE syndrome.

Clinicopathologic findings in iridocorneal endothelial syndrome and posterior polymorphous membranous dystrophy after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report the histopathologic findings of the iridocorneal endothelial (ICE) syndrome and posterior polymorphous membranous dystrophy (PPMD) in 3 patients who underwent Descemet stripping automated endothelial keratoplasty (DSAEK), and to correlate these findings with the clinical diagnosis. METHODS: Three patients with clinical findings compatible with either ICE syndrome (1 patient) or PPMD (2 patients) underwent DSAEK. The DSAEK specimens were processed for light microscopy, immunhistochemical staining for cytokeratins AE1/3 and MAK6, and electron microscopy. RESULTS: Examination of the DSAEK specimens showed multilayered endothelial cells and thickened Descemet membrane in all cases. Immunohistochemical staining for cytokeratins was positive in the endothelium in all cases. Ultrastructural examination showed a thickened Descemet membrane and wide-spaced collagen in Descemet membrane in 1 case of PPMD but not in 2 cases of ICE syndrome, including 1 case that carried the clinical diagnosis of PPMD. In 2 cases, the histopathologic evaluation of the DSAEK specimen confirmed the clinical diagnosis; however, in 1 case the pathological diagnosis was ICE syndrome, while the clinical diagnosis was PPMD. CONCLUSIONS: ICE syndrome and PPMD can be diagnosed and differentiated from one another by histopathologic evaluation of corneal specimens obtained at the time of DSAEK. We recommend submitting the corneal tissue obtained during DSAEK for pathological examination when the etiology of corneal edema is unclear.

A singular case of congenital self-healing histiocytosis with skin, liver and atypical eye involvement.

PURPOSE: To describe a rare case of congenital self-healing Langerhans cell histiocytosis (CSHLCH) presenting with atypical eye involvement. DESIGN: Case report. METHODS: A female newborn presented with purpuric lesions over the trunk, limbs, and face. Liver ultrasonography revealed hypoechogenic lesions with blurred borders. Biomicroscopy showed right posterior synechiae with fibrinoid deposits on the lens. At 7 months she presented with right acute glaucoma. RESULTS: Biomicroscopy showed the presence of inflammatory pseudo-membrane covering the anterior surface of the lens, iris, and iridocorneal angle. Ab externo trabeculotomy was performed; access to the anterior chamber with capsulorrhexis forceps permitted a peeling of the pseudo-membrane with normalization of the intraocular pressure. Histologic examination of the membrane revealed an inflammatory tissue with CD1a and S-100 positive histiocytic cells. CONCLUSIONS: This is the first case of CSHLCH describing acute glaucoma secondary to a pseudo-inflammatory membrane with typical histiocytic cells, occluding the iridocorneal angle.

Bilateral iridocorneal endothelial (ICE) syndrome with microspherophakia.

Iridocorneal endothelial syndrome is described to be a rare, usually unilateral ocular condition in young females. There are three known overlapping clinical variants of this condition namely, essential iris atrophy, Cogan-Reese and Chandler syndrome. We report a case of bilateral iridocorneal endothelial (ICE) syndrome with microspherophakia. A 25 years old female presented with microspherophakic lens dislocated into anterior chamber in right eye, and displaced inferiorly in left eye. She was also diagnosed with ICE syndrome and underwent lensectomies in both eyes. This unique combination has never been reported before.

A case of essential iris atrophy in a male patient.

Essential iris atrophy is a rare disease of abnormal proliferative corneal endothelium which usually presents with iris atrophy, corectopia, pseudopolycoria, corneal oedema and glaucoma. The disease occurs typically in one eye of a young to middle aged woman. The unusual feature in this case was that, the patient was a 36-year-old male presenting with iris atrophy, corneal oedema and uniocular glaucoma.

Ocular gene transfer of active TGF-beta induces changes in anterior segment morphology and elevated IOP in rats.

Purpose. Transforming growth factor beta (TGF-beta) is known to play a crucial role in wound healing and fibrotic tissue remodeling. A large body of evidence suggests a role for this cytokine in the pathogenesis of glaucoma; however, the mechanisms by which it affects anterior segment morphology are not well understood. Therefore, the purpose of this study was to examine the effects of TGF-beta overexpression on anterior segment morphology and subsequent effects on intraocular pressure. Methods. Adenoviral gene transfer was used to deliver active TGF-beta1 to the rat eye. Measurements of intraocular pressure were taken with a tonometer on days 0, 14, 21, and 29. Histologic analysis was undertaken to examine anterior segment morphology, and markers of matrix deposition and fibrosis were used. Results. Gene transfer of TGF-beta in the anterior segment resulted in the formation of peripheral anterior synechiae (PAS), which consisted of a fibroproliferative region of corneal endothelial cells, matrix accumulation, and decrease in trabecular meshwork expression of alpha-smooth muscle actin. These features were accompanied by ocular hypertension. Conclusions. Gene transfer of TGF-beta into the anterior segment induces aberrant PAS associated with the transition of corneal endothelial cells and subsequent matrix deposition. These features are highly reminiscent of human iridocorneal endothelial (ICE) syndrome. Gene transfer of TGF-beta can, therefore, be used to induce anatomic changes in the anterior segment in a rodent model that result in ocular hypertension.

[Morphological changes of cornea in iridocorneal endothelial syndrome under the confocal microscopy].

OBJECTIVE: To evaluate the morphological changes of cornea in iridocorneal endothelial syndrome (ICE) under the examination of in vivo confocal microscopy. METHODS: The experimental design was retrospective observation case series. Twenty-three eyes of 23 consecutive patients, each diagnosed as ICE, had their both eyes examined with the in vivo confocal microscopy (NIDEK, confoscan 3.0). The images were recorded and analyzed by software NAVIS. Measurements were performed on endothelium density, average endothelial area, the percentage of hexagonal cells and the percentage of endothelium with nuclei, and the ANOVA was done to assess the differences. RESULTS: In vivo confocal microscopy highlighted two main patterns of endothelial changes: "kite-like" and "epithelial-like" abnormal endothelium, characterised by marked hyperreflective nuclei and loss of regularity in cellular size and shape. With the progression of disease, the endothelium density and the percentage of hexagonal endothelial cells decreased, which were (1687.1 +/- 122.6), (1210.6 +/- 168.7), (947.3 +/- 145.2), (856.8 +/- 73.4) cells/mm2 and (51.5 +/- 6.3)%, (39.8 +/- 9.2)%, (32.7 +/- 8.1)%, (24.1 +/- 5.6)% respectively in detail. In contrast, the average endothelial area the percentage of endothelium with nuclei increased, which were (678.3 +/- 56.3), (928.7 +/- 96.2), (1188.5 +/- 72.6), (1337.5 +/- 60.8) microm2 and (12.6 +/- 1.4)%, (56.8 +/- 3.7)%, (78.7 +/- 5.6)%, (84.3 +/- 2.8)%. The differences all had statistical significance (F = 7.158, 7.736, 6.876, 14.452 respectively, P = 0.000). The morphology of keratocyte and endothelium were normal, compared with the contralateral healthy eyes. However, the stromal nerves became thicker and more tortuous with the disease advancement. CONCLUSIONS: The application of confocal microscopy indicates that the ICE is characterised by epithelial-like endothelial cells with hyperreflective nuclei. The technique has great potential in diagnosing ICE, especially in evaluating the disease progression.