Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia.

Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.

Axenfeld-Rieger syndrome: a novel histopathologic finding associated with corneal abnormalities.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare kind of anterior segment dysgenesis (ASD). The most common ocular features of ARS are posterior embryotoxon and iris hypoplasia, while some patients may manifest as corneal opacity and edema. However, the current understanding of how ARS affects the cornea is still incomplete. This study reports a novel histopathological finding of ARS, complicating corneal abnormalities, including congenital corneal opacity and irreversible endothelial decompensation. METHODS: This retrospective study included 6 eyes of 3 ARS patients, 5 of which underwent keratoplasty for irreversible endothelial decompensation from May 2016 to January 2019. No eye had a history of surgery. We reviewed the data of epidemiology, clinical manifestations and histopathologic examinations. RESULTS: Five eyes developed irreversible endothelial decompensation, among which 4 were born with corneal opacity. One eye exhibited transparent cornea but showed a continuous loss of endothelial cells in the absence of surgery and elevated intraocular pressure thereafter. Anterior segment optical coherence tomography photographs showed that anterior synechia existed in the area with corneal opacities, where we found the interlayer splitting of the Descemet membrane inserted by hypoplastic iris and a basement membrane-like structure under a light microscope. CONCLUSION: Anterior synechia might be associated with corneal abnormalities in ARS patients. The novel histopathologic finding revealed the internal relation between anterior segment dysgenesis and would help explore the inner mechanism of corneal abnormalities in ARS.

Imaging of the Ciliary Body: A Major Review.

PURPOSE: We conducted a systematic search of literature to understand the various methods of imaging of the ciliary body. METHODS: PubMed, Science Direct, Cochrane Library and Google Scholar were searched comprehensively and systematically to find studies related to the various modalities of ciliary body imaging. RESULTS: The various ciliary body parameters that have been described are Ciliary body thickness, Ciliary body length, ciliary muscle thickness, ciliary process length, ciliary muscle length, ciliary muscle anterior length, trabecular ciliary process distance and Iris ciliary process distance. The various angles which have been measured, which mostly have a significance in Primary angle closure glaucoma (PACG) are Iris ciliary angle, Trabecular ciliary angle, scleral ciliary process angle. Various authors have defined them in various ways with subtle differences. Plateau iris and PACG mechanisms, not forgetting malignant glaucoma are better understood with imaging of the ciliary body using the ultrasound biomicroscopy (UBM). The anterior segment optical coherence tomography (ASOCT) imaging of the ciliary body has been described albeit with its own disadvantages. A few other fields dependant on the importance of ciliary body imaging are intravitreal injections, pars plana vitrectomy, measurements for implantable collamer lens (ICL) and of utmost importance, the differentiating features of ciliary body masses. CONCLUSION: The UBM is still preferred over the ASOCT for imaging of the ciliary body. A lot of lacunae of knowledge still exists and consensus has to be reached on defining all the parameters universally. Future studies will be able to shed more light on the role of the ciliary body in the many ocular disorders mentioned in this review.

Iris Manifestations in Inadequately Treated Chronic Recurrent Vogt-Koyanagi-Harada Disease.

PURPOSE: To describe the iris changes in chronic recurrent Vogt-Koyanagi-Harada Disease (VKH). METHODS: Retrospective case series. Clinical features of 3 VKH patients who developed bilateral depigmentation of the iris are described. RESULTS: Patients had delayed diagnosis and inadequately treated chronic recurrent VKH. Patient 1 presented with bilateral multiple contiguous small granulomatous iris stromal lesions, severe diffuse iris swelling more severe near the iris root, producing peripheral iris undulations. Diffuse iris atrophy and peripheral depigmentation subsequently developed. Patient 2 presented with peripheral iris depigmentation, atrophy of the ciliary zone iris stroma and sparing of the sphincter pupillae, giving a 'sunflower appearance.' Patient 3 had extensive iris depigmentation, atrophy, and transillumination defects involving the entire iris. CONCLUSION: Uncontrolled bilateral diffuse granulomatous stromal iris inflammation leads to subsequent depigmentation, transillumination defects and atrophy, beginning in the peripheral iris. Sphincter pupillae is initially spared but complete iris atrophy may develop.

Association of peripheral anterior synechiae with anterior segment parameters in eyes with primary angle closure glaucoma.

To investigate the association of peripheral anterior synechiae (PAS) with intraocular pressure (IOP) and anterior-segment parameters in subjects with primary angle-closure glaucoma (PACG). A total of 267 subjects with PACG were recruited and underwent gonioscopy and anterior-segment optical coherence tomography (ASOCT). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750) and trabecular-iris-space-area (TISA750) at 750 µm from the scleral spur, anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Presenting IOP was defined as the first IOP reading before the initiation of IOP-lowering treatment. The mean age of the 267 subjects was 67.0 ± 8.9 years, 140 (52.4%) were male, and 246 (92.1%) were of Chinese ethnicity. PAS was present in 122 (45.7%) subjects, and was most frequently found in the superior quadrant (79.5%). Subjects with PAS had greater presenting IOP (28.7 ± 12.9 vs 22.4 ± 9.7 mmHg, p < 0.001), narrower AOD750 (p < 0.001), smaller TISA750 (p < 0.001), ACD (p = 0.04), ACA (p = 0.02), ACV (p = 0.01) and larger LV (p = 0.01) compared to PACG eyes without PAS. No significant differences were noted for iris parameters. A multivariate logistic regression analysis showed that higher presenting IOP (ß = 0.20, p < 0.001), worse visual field mean deviation (ß = - 0.20, p = 0.01) and narrower AOD750 (ß = - 0.25, p = 0.03) were the only parameters that significantly correlated with the extent of PAS in clock hours. Almost one-half of the subjects with PACG demonstrated PAS; these eyes were associated with higher presenting IOP, smaller anterior segment dimensions and more severe disease.

Atypical free-floating iridociliary pigmented epithelial cysts and secondary glaucoma in a caiman (Caiman latirostris).

We describe a case of chronic ocular trauma that resulted in fixed and free-floating, pigmented epithelial iridociliary cysts, inflammation, and secondary glaucoma in a caiman (Caiman latirostris). A 20- to 25-year-old male caiman was presented with phthisis bulbi in the right eye, and congested episcleral vessels, corneal leukoma, disorganized anterior chamber, multifocal anterior synechia, and elevated intraocular pressure in the left eye. Ocular ultrasound of the left eye revealed round structures dispersed in the anterior and posterior chambers and vitreous cavity. Bilateral enucleation was performed, and gross pathology of the left eye revealed multiple pigmented cysts attached to the iris and posterior corneal surface causing marked distortion of the anterior uvea, and free-floating in the vitreous cavity. Histopathology demonstrated heavily pigmented cystic structures of iridociliary epithelium origin carpeting the anterior segment surfaces and causing obstruction of the iridocorneal angles, leading to secondary glaucoma. To the authors' knowledge, this is the first report of iridociliary cysts in wildlife species.

Iris cyst and atypical complications / Cisto de íris e complicações atípicas

ABSTRACT The authors report the case of a male adult presenting significant ocular complications and irreversible visual impairment, resulting from the long-term progression and late diagnosis of an iris cyst in the right eye, probably secondary to trauma. The patient was admitted to Hospital Universitário Antonio Pedro with a total corneal opacity that blocked direct visualization of the anterior chamber. Ultrasound biomicroscopy was crucial for the anatomic study, and the patient was submitted to enucleation for aesthetic improvement and clarifying diagnosis. We concluded athalamia and deformation of the anterior segment, due to expansion of the cyst, led to gradual elevation of the intraocular pressure and damage of the optic nerve, resulting in visual loss.

RESUMO Relatamos o caso de um paciente com evolução e diagnóstico tardios de cisto de íris no olho direito, provavelmente secundário a trauma, com complicações importantes e baixa irreversível da visão, tendo sido admitido no Hospital Universitário Antônio Pedro já com leucoma total da córnea e câmara anterior indevassável. A biomicroscopia ultrassônica se mostrou imprescindível para o estudo anatômico, sendo o paciente finalmente submetido à enucleação, para melhora estética e elucidação diagnóstica. Concluímos que a atalamia e a desestruturação do segmento anterior, consequentes ao crescimento cístico, levaram a um gradativo aumento da pressão intraocular e lesão do nervo óptico, com consequente perda da visão.

Asymmetric choroidal hypopigmentation in a Son and mother with Waardenburg syndrome type I.

BACKGROUND: Waardenburg syndrome type I (WS-I) is a rare autosomal-dominant auditory-pigmentary disorder with limited reports in the Ophthalmic literature. MATERIALS AND METHODS: We describe the history, clinical findings and detailed retinal imaging (ultra-widefield fundus images, fundus autofluorescence and optical coherence tomography) from a patient with WS-I. CASE DESCRIPTION: Our patient had a history of white forelock and congenital hearing loss. Ophthalmic examination demonstrated iris heterochromia and highly asymmetric choroidal hypopigmentation, with generalised fundus hyperautofluorescence. Similarly, the patient's mother demonstrated highly asymmetric fundus hypopigmentation. Genetic testing confirmed a pathogenic PAX3 nonsense variant. CONCLUSION: Our report demonstrates that highly asymmetric choroidal hypopigmentation is within the clinical spectrum of WS-I. ABBREVIATIONS: OCT: Optical coherence tomography; WS-I: Waardenburg syndrome type 1.

A case of bilateral acute depigmentation of the Iris in one of two identical twins.

BACKGROUND: Bilateral Acute Depigmentation of the Iris (BADI) is a condition which was first described in a case series from Turkey by Tugal-Tutkin and Urgancioglu in (Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006). The condition is characterized by bilateral acute depigmentation and discoloration of the iris stroma, pigment dispersion, and deposition of pigment in the angle. In our case we report a patient who developed BADI after receiving pitcher plant extract injections for chronic migraine, while her identical twin sister has normal iris architecture and pigmentation and never received any pitcher plant injections. CASE PRESENTATION: Patient is a 41-year-old female with history of pitcher plant extract injections to her face for chronic migraine, who later developed bilateral depigmentation of the iris. She did not have any signs of anterior segment uveitis or iridocyclitis. She has an identical twin sister who maintained normal iris pigmentation during the entire course. CONCLUSIONS: Bilateral Acute depigmentation of the is a recently discovered condition described in the literature in Turkish patients (Tugal-Tutkun and Urgancioglu, Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006; Tugal-Tutkun et al., Ophthalmology 116(8):1552-7, 2009). This condition affects mainly young females and is characterized by acute bilateral stromal depigmentation, without other pathologic ocular findings. These patients usually maintain normal vision and do not develop significant glaucoma from pigment collecting in the anterior chamber angle. This condition can be mistaken for Fuchs' heterochromic iridocyclitis, pigment dispersion syndrome, pseudoexfoliation syndrome, and viral iridocyclitis. This is the first reported case in North America and is important for differentiation from the above pathologies. Our patient had a history of pitcher plant extract injections to the face but it is unclear if this is associated with our patient's development of BADI. As awareness of this condition progresses, a possible etiology may be elucidated.

A novel mutation of the StAR gene with congenital adrenal hyperplasia and its association with heterochromia iridis: a case report.

BACKGROUND: We report a novel mutation within the StAR gene, causing congenital adrenal hyperplasia, with the so far unreported association with heterochromia iridis. CASE PRESENTATION: In a now 15-year-old girl (born at 41 + 6 weeks of gestation) adrenal failure was diagnosed in the neonatal period based on the clinical picture with spontaneous hypoglycaemia, hyponatremia and an extremely elevated concentration of ACTH (3381 pmol/l; ref. level 1,1-10,1 pmol/l), elevated renin (836 ng/l; ref. level 5-308 ng/l), and a decreased concentration of aldosterone (410 pmol/l; ref. level 886-3540 pmol/l). In addition to hyperpigmented skin the patient exhibited sectorial heterochromia iridis. Sequence analysis of the steroidogenic acute regulatory protein (StAR) gene showed a novel homozygous mutation (c.652G > A (p.Ala218Thr), which was predicted in-silico to be possibly damaging. Under daily steroid substitution her electrolyte levels are balanced while she became obese. Puberty occurred spontaneously. CONCLUSION: A novel mutation in the StAR gene was identified in a patient with severe adrenal hypoplasia and sectorial heterochromia iridis. We discuss a causal relationship between these two rare phenotypes, i.e. whether very high levels of ACTH and alpha-MSH during early development might have disturbed early differentiation and distribution of uveal melanocytes. If confirmed in additional cases, discolorization of the iris might be considered as an additional phenotypical feature in the differential diagnosis of congenital adrenal insufficiency.

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.