Traumatic aniridia with extensive episcleral pigmentation: a case report.

BACKGROUND: Traumatic aniridia has been documented in eyes with a history of cataract extraction through a clear corneal wound. The proposed hypothesis is that the iris tissue was squeezed out from the corneal wound as it is a relative weak point. However, traumatic aniridia with extensive pigmentation of the episclera has never been reported. CASE PRESENTATION: A patient, who has surgical histories of trabeculectomy and cataract surgery many years ago, presented with refractory high intraocular pressure (IOP), almost complete loss of the iris, and diffuse pigmentation of the episclera after he had suffered from a contusion injury. In addition to numerous pigment particles and cells in the anterior chamber and a well-centered intraocular lens, protruding uvea tissue with overlying conjunctiva adjacent to the site of trabeculectomy was noted. Gonioscopy showed absence of the iris with clear view of the ciliary body. CONCLUSIONS: The distinct presentation of this case indicates that the torn iris was displaced to the trapdoor instead of the clear cornea incision and was confined to the subconjunctival space. The scleral fistula serves as a less resistant point for releasing pressure compared to a healed corneal wound when the eye encounters a contusion injury. Further treatment options to lower IOP include repeated trabeculectomy, implantation of glaucoma drainage device, and endoscopic cyclophotocoagulation. Transscleral cyclophotocoagulation may be considered only after episcleral pigmentation has become less so as to avoid the risk of surface burn.

Aniridia with lenticular and choroidal coloboma.

This case report presents a rare association of a complete aniridia with lenticular and choroidal coloboma. An 8-year-old female patient was referred to our glaucoma clinic with aniridia, nystagmus and bilateral corneal opacity with right eye being phthisical. Ultrasonography of the phthisical eye revealed the presence of an old closed funnel retinal detachment. Further examination under anaesthesia revealed lens coloboma in the inferonasal quadrant and presence of a choroidal coloboma in the left eye. The intraocular pressure was 28 mmHg with a central corneal thickness of 693 µm. A macula sparing laser barrage around the colobomatous area was done in the left eye and topical ocular hypotensives were started.

Over 10-year follow-up outcomes and failure analysis of black diaphragm intraocular lens implantation in traumatic Aniridia.

PURPOSE: To determine the over 10-year follow-up outcomes and analyse the reason for failure in patients who underwent black diaphragm intraocular lens (IOL) implantation for the management of traumatic aniridia. METHODS: Fifty-three patients underwent black diaphragm IOL implantation for the treatment of traumatic aniridia from September 1998 to August 2007. 33 eyes of 33 patients were enrolled in our study, and the mean follow-up period was 185.6 ± 36.2 months (range: 126-247 months). The primary methods employed for assessment of the safety of the IOL and the causes of failure were the ultrasound biomicroscopy (UBM) and observation during reoperation. RESULTS: In the current study, 13 patients (39.4%) who underwent IOL implantation by means of trans-scleral fixation were observed to maintain a transparent cornea and normal intraocular pressure. 20 patients (60.6%) developed corneal endothelial decompensation, and 14 patients (42.4%) developed secondary glaucoma. 27 patients were examined by means of UBM or reoperation and the position of black diaphragm IOL in 18 patients was observed to be abnormal; the IOL had shifted forward and directly contacted with the anterior chamber and even the corneal endothelium. CONCLUSION: The forward displacement of black diaphragm IOL is a direct cause of treatment failure. Although the implantation of black diaphragm IOL is an effective method of management of traumatic aniridia, the treatment should be guarded and performed in an appropriate manner. Patients should be informed regarding the need for life-long follow-up, so that the complications can be identified in a timely manner.

[Post-traumaticaniridia long after cataract surgery]. / Cas clinique. Aniridie post-traumatique à distance d'une opération de cataracte.

Post-traumatic aniridia is an uncommon complication of blunt ocular trauma. When it is completed, it represents a 360-degree tear from the root of the iris to its insertion into the ciliary body. Since the introduction of the use of corneal micro-incisions in cataract surgery, some cases of complete tear of iris root have been observed in patients who suffered from violent trauma. We report the case of a patient who has a complete aniridia after a fall, 15 years after cataract surgery.

L'aniridie post-traumatique est une complication peu fréquente d'un traumatisme oculaire à globe fermé. Lorsqu'elle est complète, il s'agit d'une déchirure sur 360° de la racine de l'iris à son insertion au corps ciliaire. Depuis l'avènement de l'utilisation de micro-incisions cornéennes en chirurgie de cataracte, la déchirure complète de la racine de l'iris a été observée sur plusieurs patients ayant subi un traumatisme violent. Nous rapportons le cas d'un patient, opéré de cataracte 15 ans auparavant, qui présente une aniridie complète suite à une chute.

Aniridia: A Rare Manifestation Of Congenital Rubella Syndrome.

A foetus affected by a congenital rubella infection can develop congenital rubella syndrome (CRS). Aniridia is the absence of iris, rarely been described in literature in association with CRS, can easily be overlooked, leading to complications e.g. glaucoma and blindness later in life. We report a case of a neonate with CRS and aniridia presenting at a tertiary care hospital.

A novel splice site variant in ITPR1 gene underlying recessive Gillespie syndrome.

Gillespie syndrome (GLSP) is a rare congenital disorder characterized by partial aniridia, hypotonia, progressive cerebellar hypoplasia, nonprogressive ataxia, and intellectual disability. All causative variants to date affect the central or the 3'-terminal domains of ITPR1 gene and exhibit autosomal recessive or dominant inheritance pattern. We investigated by exome sequencing the molecular cause of GLSP in a family composed by consanguineous healthy parents, two affected siblings and one healthy son. We found the novel splice site variant c.278_279 + 2delACGT located at the 5'-end of ITPR1. The affected siblings were homozygotes, their parents heterozygous carriers and the variant was absent in the healthy son, indicating a recessive inheritance pattern. The deletion abolished the splice-donor site at exon 5/intron 5 junction, causing the skipping of exon 5 and the generation of a premature STOP codon. The mutation is predicted to result in the synthesis of a 64-amino acids nonfunctional protein. The mutant transcript comprised >96% of ITPR1 mRNA in the affected siblings, indicating that a small amount of wild-type transcript was still present. The novel autosomal recessive mutation here reported is the first variant affecting the ITPR1 N-terminal suppressor domain, thus extending the spectrum of the pathogenetic variants in GLSP and the range of the associated clinical manifestations.

[Management of post-traumatic aphakia and aniridia: Retrospective study of 17 patients undergoing scleral-sutured artificial iris intraocular lens implantation. Management of aphakia-aniridia with scleral-sutured artificial iris intraocular lenses]. / Prise en charge de l'aphakie et de l'aniridie post-traumatiques. Étude rétrospective de 17 patients opérés d'implants intraoculaires suturés à la sclère à iris artificiel. Gestion de l'aphakie-aniridie par implants suturés à la sclère à iris artificiel.

PURPOSE: To evaluate the long-term outcomes of artificial iris intraocular lenses sutured to the sclera for managing traumatic aphakia and aniridia. METHODS: All consecutive cases receiving a Morcher® combination implant from June 2008 to February 2016 in Edouard-Herriot Hospital (Lyon, France) were included in this single-center retrospective study. Visual acuity, subjective degree of glare, quality of life and surgical complications were evaluated. RESULTS: Seventeen eyes of 17 patients were included, among which 82% were male. The mean age was 42 years. The injuries consisted of 23.5% contusion and 70.5% open globe injuries, of which 41% were globe ruptures. There was one postoperative case. A penetrating keratoplasty was performed at the same time for eight eyes. The mean follow-up was 32 months. Best-corrected visual acuity improved in 41.2%, remained the same in 17.6% and decreased in 41.2% of our cases. Distance vision averaged 1±0.25 line better and near vision 2.2±0.32 lines better when visual acuity was quantifiable before surgery. Glare improved in 80% of patients and remained stable in 20%, decreasing on average from 3.3/5 [min. 3-max. 4; SD: 0.48] before surgery to 1.9/5 [min. 0-max. 4; SD: 1.197] after surgery. Regarding the esthetic results, 78% of the patients declared themselves reasonably to very satisfied; 57% reported no limitation of activities of daily living, and 43% reported mild limitation. Ocular hypertension and glaucoma, found in 40% of eyes, were the main postoperative complications. CONCLUSION: Implantation of prosthetic iris device combined with an intraocular lens appears to be safe and effective in reducing glare disability and improving visual acuity. Close, long-term monitoring is essential for the success of this surgery.

[Visual rehabilitation of patients with large post-traumatic defects of the anterior eye segment through iris-lens diaphragm implantation]. / Sistema zritel'noi reabilitatsii patsientov s obshirnymi defektami struktur perednego otrezka glaznogo iabloka na osnove implantatsii iridokhrustalikovoi diafragmy.

The diversity of methodological approaches and lack of pathogenetically reasonable tactics for patients with combined ocular injuries became the basis for the development and systematization of surgical rehabilitation stages of patients, in whom post-traumatic cataract is combined with post-traumatic aniridia and corneal scarring. AIM: to construct a visual rehabilitation approach to patients with post-traumatic defects of the anterior eye segment following optical-reconstructive surgery that involved implantation of an iris-lens diaphragm (ILD). MATERIAL AND METHODS: We have analyzed 80 reconstructive cases with ILD implantation in patients with post-traumatic aniridia and corneal damage. These patients constituted the first study group (Group 1). We have also investigated 58 eyes with residual ametropy and stable visual function 1 year after ILD implantation before and after conducting a laser keratorefractive surgery. These patients were assigned to the second study group (Group 2). RESULTS: Rehabilitation approach to patients after anterior segment injuries that has been proposed allows to achieve high clinical and functional results and reduce the risk of intra- and postoperative complications. CONCLUSION: The proposed approach to patients after optical-reconstructive surgery with iris-lens diaphragm implantation followed by keratorefractive surgery is an effective method of visual rehabilitation of anterior eye segment post-traumatic defects.

Chronic post-operative iris prosthesis endophthalmitis in a patient with traumatic aniridia: a case report.

BACKGROUND: Post-operative endophthalmitis is a serious complication of intraocular surgery which may present acutely or chronically. Chronic post-operative endophthalmitis is characterized by decreased visual acuity, mild pain, and low-grade uveitis several weeks or months after intraocular surgery which may be responsive to corticosteroids, but recur upon tapering. Low virulence organisms such as Propionibacterium acnes are the most common culprit organisms, and treatment most often consists of both intravitreal antibiotic injections and surgery. Aniridia is a condition defined by total or partial loss of the iris and leads to decreased visual quality marked by glare and photophobia. Treatment of complex or severe cases of traumatic aniridia in which surgical repair is difficult may consist of implantation of iris prostheses, devices designed to reduce symptoms of aniridia. Though chronic, post-operative endophthalmitis has been associated with most intraocular surgeries including intraocular lens implantation after cataract removal, it has never been described in a patient with an iris prosthesis. CASE PRESENTATION: In this case report, we describe the case of a 49 year old, male construction worker with traumatic aniridia who experienced chronic, recurrent low-grade intraocular inflammation and irritation for months after implantation of the Ophtec 311 prosthetic iris. Symptoms and signs of inflammation improved temporarily with sub-Tenon's capsule triamcinolone injections. Ultimately after more than 2 post-operative years, the iris prosthesis was explanted, and intravitreal cultures showed P. acnes growth after 5 days. Intravitreal antibiotics treated the infection successfully. CONCLUSIONS: To our knowledge, this is the first reported case of chronic, post-operative endophthalmitis in a patient with an iris prosthesis. Chronic, post-operative endophthalmitis may be a difficult to identify in the context of traumatic aniridia and iris prosthesis implantation due to other potential etiologies of chronic intraocular inflammation such as implant-induced chafing. Clinicians should suspect chronic, post-operative endophthalmitis in any case of recurrent, low-grade intraocular inflammation.

Recessive and Dominant De Novo ITPR1 Mutations Cause Gillespie Syndrome.

Gillespie syndrome (GS) is a rare variant form of aniridia characterized by non-progressive cerebellar ataxia, intellectual disability, and iris hypoplasia. Unlike the more common dominant and sporadic forms of aniridia, there has been no significant association with PAX6 mutations in individuals with GS and the mode of inheritance of the disease had long been regarded as uncertain. Using a combination of trio-based whole-exome sequencing and Sanger sequencing in five simplex GS-affected families, we found homozygous or compound heterozygous truncating mutations (c.4672C>T [p.Gln1558(∗)], c.2182C>T [p.Arg728(∗)], c.6366+3A>T [p.Gly2102Valfs5(∗)], and c.6664+5G>T [p.Ala2221Valfs23(∗)]) and de novo heterozygous mutations (c.7687_7689del [p.Lys2563del] and c.7659T>G [p.Phe2553Leu]) in the inositol 1,4,5-trisphosphate receptor type 1 gene (ITPR1). ITPR1 encodes one of the three members of the IP3-receptors family that form Ca(2+) release channels localized predominantly in membranes of endoplasmic reticulum Ca(2+) stores. The truncation mutants, which encompass the IP3-binding domain and varying lengths of the modulatory domain, did not form functional channels when produced in a heterologous cell system. Furthermore, ITPR1 p.Lys2563del mutant did not form IP3-induced Ca(2+) channels but exerted a negative effect when co-produced with wild-type ITPR1 channel activity. In total, these results demonstrate biallelic and monoallelic ITPR1 mutations as the underlying genetic defects for Gillespie syndrome, further extending the spectrum of ITPR1-related diseases.

A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect.

Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions.

Aniridia after blunt trauma and presumed wound dehiscence in a pseudophakic eye.

This was a report about a pseudophakic patient who experienced isolated total aniridia without damage to other intraocular structures following blunt trauma to the eye. This patient had a history of uneventful cataract surgery using a small clear corneal incision (CCI). This 71-year-old male presented at our clinic with glare in his left eye. He reported that he had fallen down while drunk and struck his left eye against a stone on the road 15 days earlier. He had undergone cataract surgery on his left eye nine months before the accident at another eye clinic. Slit-lamp examination showed total aniridia in his left eye, but there was no hyphema or cells in the anterior chamber. The intraocular lens in his left eye was stable, without decentration, dislocation, or zonular dehiscence and remained in an intact capsular bag. Review of the medical records from the surgical clinic at which he had undergone cataract surgery indicated no specific findings for any intraocular structure including the iris. He had previously undergone an uneventful phacoemulsification for his left eye through a 2.2 mm CCI, followed by the implantation of a single piece acrylic intraocular lens inside an intact capsular bag. This report showed that small-sized CCIs can be opened postoperatively by trauma and that this can result in isolated total aniridia without damage to other intraocular structures.

Combined transscleral fixation of an artificial iris prosthesis with an intraocular lens.

Post-traumatic aniridia combined with aphakia may be seen after globe injury. Aside from esthetic aspects, partial or total loss of the iris tissue may also be related to various degrees of glare and photophobia. Such patients suffer from severe visual impairment secondary to aphakia. Herein we describe a novel surgical technique for the management of an aphakic eye with traumatic aniridia for a patient who underwent transscleral fixation of a custom-tailored artificial iris prosthesis combined with a rigid intraocular lens (IOL). Tight suturing of the IOL haptic eyelets on the silicone iris prosthesis and fixation of such a complex to the scleral wall may provide excellent cosmetic and functional outcomes in aphakic eyes with aniridia.

Aniridia after blunt trauma and presumed wound dehiscence in a pseudophakic eye / Aniridia após trauma contuso e deiscência presumida da incisão em um olho pseudofácico

ABSTRACT This was a report about a pseudophakic patient who experienced isolated total aniridia without damage to other intraocular structures following blunt trauma to the eye. This patient had a history of uneventful cataract surgery using a small clear corneal incision (CCI). This 71-year-old male presented at our clinic with glare in his left eye. He reported that he had fallen down while drunk and struck his left eye against a stone on the road 15 days earlier. He had undergone cataract surgery on his left eye nine months before the accident at another eye clinic. Slit-lamp examination showed total aniridia in his left eye, but there was no hyphema or cells in the anterior chamber. The intraocular lens in his left eye was stable, without decentration, dislocation, or zonular dehiscence and remained in an intact capsular bag. Review of the medical records from the surgical clinic at which he had undergone cataract surgery indicated no specific findings for any intraocular structure including the iris. He had previously undergone an uneventful phacoemulsification for his left eye through a 2.2 mm CCI, followed by the implantation of a single piece acrylic intraocular lens inside an intact capsular bag. This report showed that small-sized CCIs can be opened postoperatively by trauma and that this can result in isolated total aniridia without damage to other intraocular structures.

RESUMO Relatamos um paciente com história de cirurgia de catarata sem intercorrências usando uma pequena incisão na córnea clara (CCI), que apresentou aniridia total isolada, sem danos a outras estruturas intraoculares, após trauma contuso no olho. Um homem de 71 anos de idade apresentou-se em nossa clínica referindo brilho no olho esquerdo. Ele relatou que, 15 dias antes, havia caído enquanto estava bêbado e atingiu seu olho esquerdo contra uma pedra na estrada. Ele havia passado por uma cirurgia de catarata no olho esquerdo, nove meses antes do acidente em outro serviço. Exame de lâmpada de fenda mostrou aniridia total de olho esquerdo, sem hifema ou células na câmara anterior. A lente intraocular no olho esquerdo ficou estável, com o saco capsular restante intacto, sem descentralização, luxação ou deiscência zonular. O exame dos registros médicos do serviço em que ele havia se submetido a uma cirurgia de catarata não mostraram relatos específicos a qualquer estrutura intraocular, incluindo a íris. O olho esquerdo fora submetido à facoemulsificação sem complicações, através de um CCI de 2,2 mm, seguido pela implantação de uma lente intraocular acrílica peça única dentro do saco capsular intacto. Este relatório mostra que, mesmo pequenas CCIs podem ser abertas no pós-operatório por trauma e que isso pode resultar em aniridia total isolada, sem danos a outras estruturas intraoculares.

Combined transscleral fixation of an artificial iris prosthesis with an intraocular lens / Combinação de fixação transescleral de prótese de íris artificial com lente intraocular

ABSTRACT Post-traumatic aniridia combined with aphakia may be seen after globe injury. Aside from esthetic aspects, partial or total loss of the iris tissue may also be related to various degrees of glare and photophobia. Such patients suffer from severe visual impairment secondary to aphakia. Herein we describe a novel surgical technique for the management of an aphakic eye with traumatic aniridia for a patient who underwent transscleral fixation of a custom-tailored artificial iris prosthesis combined with a rigid intraocular lens (IOL). Tight suturing of the IOL haptic eyelets on the silicone iris prosthesis and fixation of such a complex to the scleral wall may provide excellent cosmetic and functional outcomes in aphakic eyes with aniridia.

RESUMO Aniridia pós-traumática combinada com afacia pode ser observada após lesões do globo ocular. Além do ponto de vista estético, a perda parcial ou total do tecido da íris também pode estar relacionada com vários graus de ofuscamento e fotofobia. Estes pacientes sofrem de deficiência visual grave secundária a afacia. Relata-se uma técnica cirúrgica inovadora para tratamento de um olho com afacia associada à aniridia traumática que foi submetido à fixação transescleral de uma prótese de íris artificial feita sob medida combinada com uma lente intraocular rígida (IOL). A sutura das alças da IOL sobre a prótese iriana de silicone, e a fixação desse complexo na parede escleral podem proporcionar excelente resultado estético e funcional em olhos afácicos com aniridia.

Fatty acid transport protein 1 can compensate for fatty acid transport protein 4 in the developing mouse epidermis.

Fatty acid transport protein (FATP) 4 is one of a family of six FATPs that facilitate long- and very-long-chain fatty acid uptake. Mice lacking FATP4 are born with tight, thick skin and a defective barrier; they die neonatally because of dehydration and restricted movements. Mutations in SLC27A4, the gene encoding FATP4, cause ichthyosis prematurity syndrome (IPS), characterized by premature birth, respiratory distress, and edematous skin with severe ichthyotic scaling. Symptoms of surviving patients become mild, although atopic manifestations are common. We previously showed that suprabasal keratinocyte expression of a Fatp4 transgene in Fatp4 mutant skin rescues the lethality and ameliorates the skin phenotype. Here we tested the hypothesis that FATP1, the closest FATP4 homolog, can compensate for the lack of FATP4 in our mouse model of IPS, as it might do postnatally in IPS patients. Transgenic expression of FATP1 in suprabasal keratinocytes rescued the phenotype of Fatp4 mutants, and FATP1 sorted to the same intracellular organelles as endogenous FATP4. Thus, FATP1 and FATP4 likely have overlapping substrate specificities, enzymatic activities, and biological functions. These results suggest that increasing expression of FATP1 in suprabasal keratinocytes could normalize the skin of IPS patients and perhaps prevent the atopic manifestations.