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Purpose: The purpose of this study is to study the frequency, surgical transplantation technique and outcome in patients with aniridia-related keratopathy (ARK) with two-year follow-up period. Methods: A retrospective registry-study including all ARK cases performed in Sweden and Denmark between 2001 and 2016 and registered in the Swedish Cornea Transplant Registry. Results: A total of 36 eyes of 26 patients were subjected to corneal transplantation due to ARK during 2001 to 2016. Penetrating keratoplasty (PK) was the procedure of choice in 58.3% (n = 21) of the eyes, followed by a combination of PK and limbal stem cell transplantation in 13.9% (n = 5) and keratolimbal allograft in 13.9% (n = 5). Boston keratoprosthesis was used in 8.3% (n = 3), and anterior lamellar keratoplasty in 5.6% (n = 2). Thirteen of the procedures (36.1%) were retransplantations. Two years after surgery 26 cases were available to follow-up of which 16 of the grafts were functioning (61.5%). The median visual acuity showed a trend of improvement from hand motion to counting fingers. Conclusions: A majority of the ARK cases (61.5%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes. Despite the introduction of limbal stem cell transplantation as a suitable treatment, PK was the most common surgical method in the present study.

Purpose: The purpose of this study is to study the frequency, surgical transplantation technique and outcome in patients with aniridia-related keratopathy (ARK) with two-year follow-up period. Methods: A retrospective registry-study including all ARK cases performed in Sweden and Denmark between 2001 and 2016 and registered in the Swedish Cornea Transplant Registry. Results: A total of 36 eyes of 26 patients were subjected to corneal transplantation due to ARK during 2001 to 2016. Penetrating keratoplasty (PK) was the procedure of choice in 58.3% (n = 21) of the eyes, followed by a combination of PK and limbal stem cell transplantation in 13.9% (n = 5) and keratolimbal allograft in 13.9% (n = 5). Boston keratoprosthesis was used in 8.3% (n = 3), and anterior lamellar keratoplasty in 5.6% (n = 2). Thirteen of the procedures (36.1%) were retransplantations. Two years after surgery 26 cases were available to follow-up of which 16 of the grafts were functioning (61.5%). The median visual acuity showed a trend of improvement from hand motion to counting fingers. Conclusions: A majority of the ARK cases (61.5%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes. Despite the introduction of limbal stem cell transplantation as a suitable treatment, PK was the most common surgical method in the present study.

Purpose: The purpose of this study is to study the frequency, surgical transplantation technique and outcome in patients with aniridia-related keratopathy (ARK) with two-year follow-up period. Methods: A retrospective registry-study including all ARK cases performed in Sweden and Denmark between 2001 and 2016 and registered in the Swedish Cornea Transplant Registry. Results: A total of 36 eyes of 26 patients were subjected to corneal transplantation due to ARK during 2001 to 2016. Penetrating keratoplasty (PK) was the procedure of choice in 58.3% (n = 21) of the eyes, followed by a combination of PK and limbal stem cell transplantation in 13.9% (n = 5) and keratolimbal allograft in 13.9% (n = 5). Boston keratoprosthesis was used in 8.3% (n = 3), and anterior lamellar keratoplasty in 5.6% (n = 2). Thirteen of the procedures (36.1%) were retransplantations. Two years after surgery 26 cases were available to follow-up of which 16 of the grafts were functioning (61.5%). The median visual acuity showed a trend of improvement from hand motion to counting fingers. Conclusions: A majority of the ARK cases (61.5%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes. Despite the introduction of limbal stem cell transplantation as a suitable treatment, PK was the most common surgical method in the present study.

Pathogenic variants in more than 14 genes have been implicated in monogenic diabetes; however, a significant fraction of individuals with young-onset diabetes and a strong family history of diabetes have unknown genetic etiology. To identify novel pathogenic alleles for monogenic diabetes, we performed whole-genome sequencing (WGS) on four related individuals with type 2 diabetes - including one individual diagnosed at the age of 31 years - that were negative for mutations in known monogenic diabetes genes. The individuals were ascertained from a large case-control study and had a multi-generation family history of diabetes. Identity-by-descent (IBD) analysis revealed that the four individuals represent two sib-pairs that are third-degree relatives. A novel missense mutation (p.P81S) in the PAX6 gene was one of eight rare coding variants across the genome shared IBD by all individuals and was inherited from affected mothers in both sib-pairs. The mutation affects a highly conserved amino acid located in the paired-domain of PAX6 - a hotspot for missense mutations that cause aniridia and other eye abnormalities. However, no eye-related phenotype was observed in any individual. The well-established functional role of PAX6 in glucose-induced insulin secretion and the co-segregation of diabetes in families with aniridia provide compelling support for the pathogenicity of this mutation for diabetes. The mutation could be classified as "likely pathogenic" with a posterior probability of 0.975 according to the ACMG/AMP guidelines. This is the first PAX6 missense mutation that is likely pathogenic for autosomal-dominant adult-onset diabetes without eye abnormalities.

Purpose: The purpose of this study is to study the frequency, surgical transplantation technique and outcome in patients with aniridia-related keratopathy (ARK) with two-year follow-up period. Methods: A retrospective registry-study including all ARK cases performed in Sweden and Denmark between 2001 and 2016 and registered in the Swedish Cornea Transplant Registry. Results: A total of 36 eyes of 26 patients were subjected to corneal transplantation due to ARK during 2001 to 2016. Penetrating keratoplasty (PK) was the procedure of choice in 58.3% (n = 21) of the eyes, followed by a combination of PK and limbal stem cell transplantation in 13.9% (n = 5) and keratolimbal allograft in 13.9% (n = 5). Boston keratoprosthesis was used in 8.3% (n = 3), and anterior lamellar keratoplasty in 5.6% (n = 2). Thirteen of the procedures (36.1%) were retransplantations. Two years after surgery 26 cases were available to follow-up of which 16 of the grafts were functioning (61.5%). The median visual acuity showed a trend of improvement from hand motion to counting fingers. Conclusions: A majority of the ARK cases (61.5%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes. Despite the introduction of limbal stem cell transplantation as a suitable treatment, PK was the most common surgical method in the present study.

Purpose: The purpose of this study is to study the frequency, surgical transplantation technique and outcome in patients with aniridia-related keratopathy (ARK) with two-year follow-up period. Methods: A retrospective registry-study including all ARK cases performed in Sweden and Denmark between 2001 and 2016 and registered in the Swedish Cornea Transplant Registry. Results: A total of 36 eyes of 26 patients were subjected to corneal transplantation due to ARK during 2001 to 2016. Penetrating keratoplasty (PK) was the procedure of choice in 58.3% (n = 21) of the eyes, followed by a combination of PK and limbal stem cell transplantation in 13.9% (n = 5) and keratolimbal allograft in 13.9% (n = 5). Boston keratoprosthesis was used in 8.3% (n = 3), and anterior lamellar keratoplasty in 5.6% (n = 2). Thirteen of the procedures (36.1%) were retransplantations. Two years after surgery 26 cases were available to follow-up of which 16 of the grafts were functioning (61.5%). The median visual acuity showed a trend of improvement from hand motion to counting fingers. Conclusions: A majority of the ARK cases (61.5%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes. Despite the introduction of limbal stem cell transplantation as a suitable treatment, PK was the most common surgical method in the present study.

Purpose: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). Design: Multicenter, observational study. Participants: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). Methods: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. Main Outcome Measures: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS–), molecular diagnosis, and visual acuity (VA). Results: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS– (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky–Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. Conclusions: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms

Purpose: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). Design: Multicenter, observational study. Participants: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). Methods: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. Main Outcome Measures: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS–), molecular diagnosis, and visual acuity (VA). Results: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS– (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky–Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. Conclusions: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms

There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.

Aim: To describe our results with HumanOptics IOL-ArtificialIris complex in post traumatic aphakia and aniridia.Methods: Retrospective, single-surgeon chart review of cases in which aniridia and aphakia were corrected using HumanOptics IOL-ArtificialIris complex sutured to the sclera with Gore-Tex® sutures and coupled with the Akreos® IOL (Bausch&Lomb). Results: The authors present four cases of ocular trauma with globe rupture. For every patient, posterior vitrectomy was done and an artificial iris-lens diaphragm was sutured to the sclera. All patients had a good functional and cosmetic outcome.Conclusions: Surgical implantation of the HumanOptics IOL-ArtificialIris complex coupled with the Akreos® IOL was successful in alleviating post-trauma aphakia and aniridia related visual impairment.

Introduction Aniridia is a rare, sight-threatening ocular disorder characterised by partial or complete absence of the iris. It can affect multiple ocular structures and lead to visual complications. According to our knowledge, there is currently no recent published research on aniridia in the South African population, thus it would be beneficial to investigate the prevalence of aniridia and describe the ocular and visual complications in South Africa. Therefore, the aim of this research was to determine the prevalence of aniridia among learners in visually impaired schools in central South Africa (Free State and North West) and to describe its visual and ocular complications. In order to achieve the aim, the number of participants that had partial and complete aniridia was determined using an ophthalmoscope. Thereafter, the visual and ocular complications in participants with aniridia were determined. Methods A prospective descriptive study was conducted on learners in three visually impaired schools in central South Africa. A total of 117 consenting learners were screened with an ophthalmoscope to determine the presence or absence of aniridia and only the participants identified with aniridia were further examined. The visual acuity of the participants with aniridia was determined using a logMAR visual acuity chart, the refractive error was determined using an autorefractor, the intraocular pressure was measured using an iCare tonometer to determine the risk for glaucoma and the anterior and posterior segment of the eye was examined using a slit lamp, 90D lens and gonioscopy lens to determine the complications associated with aniridia. Results for each participant were recorded and participants who required further management were referred to the local Ophthalmology clinic. Data analysis was performed by the Department of Biostatistics (University of the Free State). Prevalence was calculated by dividing the number of participants with aniridia by the total number

Aniridia is a congenital autosomal dominant, bilateral, panocular condition, caused by haploinsufficiency of the Pax6 transcription factor. Aniridia-related keratopathy (ARK) significantly affects vision and quality of life in these patients. ARK is a chronic progressive keratopathy comprising limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions and corneal vascular pannus that typically only appear after childhood. The aims were i) to evaluate the structural changes and ii) cell signaling pathways, including the Notch1, Sonic Hedgehog (SHH), mTOR and Wnt/beta-catenin cell signaling pathways in naïve and surgically treated corneas of aniridia cases with advanced ARK and comparing with normal human adult and fetal corneas and iii) to develop a corneal cell culture model of aniridia. Naïve ARK corneas removed at the time of the first transplantation and ARK corneal buttons removed after a failed keratolimbal allograft and failed centered and decentered transplantations were included. These were compared with normal human adult and fetal (10-11 and 20 weeks) corneas. Sections were studied with immunofluorescence using antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor a11 integrin and laminin a3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, a-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68); antibodies against Pax6 and keratin 13; and antibodies against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta- catenin), Sonic Hedgehog (Gli1; Hes1) and mTOR (mTOR1; rpS6) signaling pathways. An in vitro cell culture model of mutant PAX6 corneal cells, obtained with CRISPR was created to study the same signaling pathways with Western blot and RT-qPCR. All ARK corneas and transplanted corneal buttons presented sim

Aniridia is a congenital autosomal dominant, bilateral, panocular condition, caused by haploinsufficiency of the Pax6 transcription factor. Aniridia-related keratopathy (ARK) significantly affects vision and quality of life in these patients. ARK is a chronic progressive keratopathy comprising limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions and corneal vascular pannus that typically only appear after childhood. The aims were i) to evaluate the structural changes and ii) cell signaling pathways, including the Notch1, Sonic Hedgehog (SHH), mTOR and Wnt/beta-catenin cell signaling pathways in naïve and surgically treated corneas of aniridia cases with advanced ARK and comparing with normal human adult and fetal corneas and iii) to develop a corneal cell culture model of aniridia. Naïve ARK corneas removed at the time of the first transplantation and ARK corneal buttons removed after a failed keratolimbal allograft and failed centered and decentered transplantations were included. These were compared with normal human adult and fetal (10-11 and 20 weeks) corneas. Sections were studied with immunofluorescence using antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor a11 integrin and laminin a3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, a-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68); antibodies against Pax6 and keratin 13; and antibodies against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta- catenin), Sonic Hedgehog (Gli1; Hes1) and mTOR (mTOR1; rpS6) signaling pathways. An in vitro cell culture model of mutant PAX6 corneal cells, obtained with CRISPR was created to study the same signaling pathways with Western blot and RT-qPCR. All ARK corneas and transplanted corneal buttons presented sim

Aniridia is a congenital autosomal dominant, bilateral, panocular condition, caused by haploinsufficiency of the Pax6 transcription factor. Aniridia-related keratopathy (ARK) significantly affects vision and quality of life in these patients. ARK is a chronic progressive keratopathy comprising limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions and corneal vascular pannus that typically only appear after childhood. The aims were i) to evaluate the structural changes and ii) cell signaling pathways, including the Notch1, Sonic Hedgehog (SHH), mTOR and Wnt/beta-catenin cell signaling pathways in naïve and surgically treated corneas of aniridia cases with advanced ARK and comparing with normal human adult and fetal corneas and iii) to develop a corneal cell culture model of aniridia. Naïve ARK corneas removed at the time of the first transplantation and ARK corneal buttons removed after a failed keratolimbal allograft and failed centered and decentered transplantations were included. These were compared with normal human adult and fetal (10-11 and 20 weeks) corneas. Sections were studied with immunofluorescence using antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor a11 integrin and laminin a3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, a-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68); antibodies against Pax6 and keratin 13; and antibodies against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta- catenin), Sonic Hedgehog (Gli1; Hes1) and mTOR (mTOR1; rpS6) signaling pathways. An in vitro cell culture model of mutant PAX6 corneal cells, obtained with CRISPR was created to study the same signaling pathways with Western blot and RT-qPCR. All ARK corneas and transplanted corneal buttons presented sim

Aniridia is a congenital autosomal dominant, bilateral, panocular condition, caused by haploinsufficiency of the Pax6 transcription factor. Aniridia-related keratopathy (ARK) significantly affects vision and quality of life in these patients. ARK is a chronic progressive keratopathy comprising limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions and corneal vascular pannus that typically only appear after childhood. The aims were i) to evaluate the structural changes and ii) cell signaling pathways, including the Notch1, Sonic Hedgehog (SHH), mTOR and Wnt/beta-catenin cell signaling pathways in naïve and surgically treated corneas of aniridia cases with advanced ARK and comparing with normal human adult and fetal corneas and iii) to develop a corneal cell culture model of aniridia. Naïve ARK corneas removed at the time of the first transplantation and ARK corneal buttons removed after a failed keratolimbal allograft and failed centered and decentered transplantations were included. These were compared with normal human adult and fetal (10-11 and 20 weeks) corneas. Sections were studied with immunofluorescence using antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor a11 integrin and laminin a3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, a-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68); antibodies against Pax6 and keratin 13; and antibodies against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta- catenin), Sonic Hedgehog (Gli1; Hes1) and mTOR (mTOR1; rpS6) signaling pathways. An in vitro cell culture model of mutant PAX6 corneal cells, obtained with CRISPR was created to study the same signaling pathways with Western blot and RT-qPCR. All ARK corneas and transplanted corneal buttons presented sim

Aniridia is a congenital autosomal dominant, bilateral, panocular condition, caused by haploinsufficiency of the Pax6 transcription factor. Aniridia-related keratopathy (ARK) significantly affects vision and quality of life in these patients. ARK is a chronic progressive keratopathy comprising limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions and corneal vascular pannus that typically only appear after childhood. The aims were i) to evaluate the structural changes and ii) cell signaling pathways, including the Notch1, Sonic Hedgehog (SHH), mTOR and Wnt/beta-catenin cell signaling pathways in naïve and surgically treated corneas of aniridia cases with advanced ARK and comparing with normal human adult and fetal corneas and iii) to develop a corneal cell culture model of aniridia. Naïve ARK corneas removed at the time of the first transplantation and ARK corneal buttons removed after a failed keratolimbal allograft and failed centered and decentered transplantations were included. These were compared with normal human adult and fetal (10-11 and 20 weeks) corneas. Sections were studied with immunofluorescence using antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor a11 integrin and laminin a3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, a-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68); antibodies against Pax6 and keratin 13; and antibodies against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta- catenin), Sonic Hedgehog (Gli1; Hes1) and mTOR (mTOR1; rpS6) signaling pathways. An in vitro cell culture model of mutant PAX6 corneal cells, obtained with CRISPR was created to study the same signaling pathways with Western blot and RT-qPCR. All ARK corneas and transplanted corneal buttons presented sim

La aniridia es una enfermedad rara, congénita y hereditaria que afecta a la totalidad del desarrollo ocular, destacando la hipoplasia de iris como signo más llamativo, pero lleva asociada distintas complicaciones como ojo seco, catarata congénita, glaucoma, hipoplasia foveal y afectación del nervio óptico; además de poder estar relacionada con síndromes sistémicos. Nuestros objetivos son realizar una búsqueda bibliográfica sobre la relación ojo seco y aniridia, conocer la severidad de los síntomas de ojo seco en los pacientes de aniridia españoles y realizar una guía de cuidados. Metodología: fase I: revisión de artículos científicos consultando las bases de datos de Teseo, Google académico, Pubmed, ScienceDirect y la biblioteca de la Universidad de Valladolid. Se escogieron solo los que relacionaban ojo seo y aniridia. Fase II: estudio observacional descriptivo transversal. Fase I: se seleccionaron 4 artículos. Respecto a los diseños de los artículos científicos localizados hubo un estudio descriptivo de series de casos, un estudio descriptivo observacional longitudinal, un estudio descriptivo observacional transversal y un estudio de casos y controles. Fase II: se utilizó el cuestionario ocular sufarce disease index (OSDI). De los 23 encuestados, el 91,3% padecían síntomas severos de ojo seco., Máster en Enfermería Oftalmológica

La aniridia es una enfermedad rara, congénita y hereditaria que afecta a la totalidad del desarrollo ocular, destacando la hipoplasia de iris como signo más llamativo, pero lleva asociada distintas complicaciones como ojo seco, catarata congénita, glaucoma, hipoplasia foveal y afectación del nervio óptico; además de poder estar relacionada con síndromes sistémicos. Nuestros objetivos son realizar una búsqueda bibliográfica sobre la relación ojo seco y aniridia, conocer la severidad de los síntomas de ojo seco en los pacientes de aniridia españoles y realizar una guía de cuidados. Metodología: fase I: revisión de artículos científicos consultando las bases de datos de Teseo, Google académico, Pubmed, ScienceDirect y la biblioteca de la Universidad de Valladolid. Se escogieron solo los que relacionaban ojo seo y aniridia. Fase II: estudio observacional descriptivo transversal. Fase I: se seleccionaron 4 artículos. Respecto a los diseños de los artículos científicos localizados hubo un estudio descriptivo de series de casos, un estudio descriptivo observacional longitudinal, un estudio descriptivo observacional transversal y un estudio de casos y controles. Fase II: se utilizó el cuestionario ocular sufarce disease index (OSDI). De los 23 encuestados, el 91,3% padecían síntomas severos de ojo seco., Máster en Enfermería Oftalmológica

El avance tecnológico y científico en el campo de la optometría ha hecho posible una gran variedad de soluciones ante problemas visuales asociados con la sintomatología de la disminución de agudeza visual, deslumbramientos y/o la presencia de aberraciones en el ojo. Sin embargo, no todos los métodos presentan la misma eficacia, por lo que es importante valorar qué soluciones de las existentes muestran mejores resultados sin olvidar aspectos tan importantes como la comodidad y la estética, para acceder a una salud visual óptima. En este artículo serán analizadas de forma piloto la eficacia de las lentes de contacto tintadas catalogadas como morfo-funcionales (LCMF) en patologías relacionadas con anomalías del iris.

La aniridia es una enfermedad rara, congénita y hereditaria que afecta a la totalidad del desarrollo ocular, destacando la hipoplasia de iris como signo más llamativo, pero lleva asociada distintas complicaciones como ojo seco, catarata congénita, glaucoma, hipoplasia foveal y afectación del nervio óptico; además de poder estar relacionada con síndromes sistémicos. Nuestros objetivos son realizar una búsqueda bibliográfica sobre la relación ojo seco y aniridia, conocer la severidad de los síntomas de ojo seco en los pacientes de aniridia españoles y realizar una guía de cuidados. Metodología: fase I: revisión de artículos científicos consultando las bases de datos de Teseo, Google académico, Pubmed, ScienceDirect y la biblioteca de la Universidad de Valladolid. Se escogieron solo los que relacionaban ojo seo y aniridia. Fase II: estudio observacional descriptivo transversal. Fase I: se seleccionaron 4 artículos. Respecto a los diseños de los artículos científicos localizados hubo un estudio descriptivo de series de casos, un estudio descriptivo observacional longitudinal, un estudio descriptivo observacional transversal y un estudio de casos y controles. Fase II: se utilizó el cuestionario ocular sufarce disease index (OSDI). De los 23 encuestados, el 91,3% padecían síntomas severos de ojo seco., Máster en Enfermería Oftalmológica

La aniridia es una enfermedad rara, congénita y hereditaria que afecta a la totalidad del desarrollo ocular, destacando la hipoplasia de iris como signo más llamativo, pero lleva asociada distintas complicaciones como ojo seco, catarata congénita, glaucoma, hipoplasia foveal y afectación del nervio óptico; además de poder estar relacionada con síndromes sistémicos. Nuestros objetivos son realizar una búsqueda bibliográfica sobre la relación ojo seco y aniridia, conocer la severidad de los síntomas de ojo seco en los pacientes de aniridia españoles y realizar una guía de cuidados. Metodología: fase I: revisión de artículos científicos consultando las bases de datos de Teseo, Google académico, Pubmed, ScienceDirect y la biblioteca de la Universidad de Valladolid. Se escogieron solo los que relacionaban ojo seo y aniridia. Fase II: estudio observacional descriptivo transversal. Fase I: se seleccionaron 4 artículos. Respecto a los diseños de los artículos científicos localizados hubo un estudio descriptivo de series de casos, un estudio descriptivo observacional longitudinal, un estudio descriptivo observacional transversal y un estudio de casos y controles. Fase II: se utilizó el cuestionario ocular sufarce disease index (OSDI). De los 23 encuestados, el 91,3% padecían síntomas severos de ojo seco., Máster en Enfermería Oftalmológica

El avance tecnológico y científico en el campo de la optometría ha hecho posible una gran variedad de soluciones ante problemas visuales asociados con la sintomatología de la disminución de agudeza visual, deslumbramientos y/o la presencia de aberraciones en el ojo. Sin embargo, no todos los métodos presentan la misma eficacia, por lo que es importante valorar qué soluciones de las existentes muestran mejores resultados sin olvidar aspectos tan importantes como la comodidad y la estética, para acceder a una salud visual óptima. En este artículo serán analizadas de forma piloto la eficacia de las lentes de contacto tintadas catalogadas como morfo-funcionales (LCMF) en patologías relacionadas con anomalías del iris.

PurposeTo discuss problems associated with the implantation of two Morcher iris diaphragm models.MethodsWe describe the history, intraoperative complications, and postoperative complications of 5 patients with specific Morcher iris implants.ResultsWe implanted Morcher 50D devices in 1 patient and Morcher 96S devices in 4 patients. Complications included postoperative rotation, device mis-sizing, difficult intraoperative rotation, zonular dehiscence, and intraoperative hemorrhage.ConclusionArtificial iris implantation has a steep learning curve. With widespread availability on the horizon in the United States, the sharing of surgical experiences is key to achieving the best outcomes for patients.

PurposeTo discuss problems associated with the implantation of two Morcher iris diaphragm models.MethodsWe describe the history, intraoperative complications, and postoperative complications of 5 patients with specific Morcher iris implants.ResultsWe implanted Morcher 50D devices in 1 patient and Morcher 96S devices in 4 patients. Complications included postoperative rotation, device mis-sizing, difficult intraoperative rotation, zonular dehiscence, and intraoperative hemorrhage.ConclusionArtificial iris implantation has a steep learning curve. With widespread availability on the horizon in the United States, the sharing of surgical experiences is key to achieving the best outcomes for patients.

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., SCOPUS: ar.j, info:eu-repo/semantics/published

PurposeTo evaluate the safety and efficacy of Morcher 96F iris diaphragm implantation to manage small defects of the human iris.SettingJules Stein Eye Institute, UCLA, Los Angeles, California, USA.DesignProspective nonrandomized interventional case series.MethodsDemographic, preoperative, and postoperative data of patients who had implantation of the modified capsular tension ring (CTR) and followed to 1 year were reviewed. Safety measures included loss of corrected distance visual acuity (CDVA), perioperative complications, adverse events, and secondary surgical interventions. Efficacy measures included CDVA with glare, daytime and nighttime glare symptom scores, and subjective cosmesis scores.ResultsSixteen patients had CTR implantation. There was a statistically significant improvement in the median CDVA of 2.5 Snellen lines (P < .01), with 4 patients having minor decreases in CDVA for reasons unrelated to the device. There were no intraoperative complications. Three adverse events were reported: 1 ocular hypertension, 1 postoperative retinal detachment, and 1 25-degree rotation of the CTR. There were 4 secondary surgical interventions. There was a statistically significant improvement in the median CDVA with glare of 8 Snellen lines (P < .01), but 2 patients had a decrease in CDVA with glare for reasons unrelated to the device. There were statistically significant improvements in the median daytime and nighttime glare symptom scores of 5 points and 4 points, respectively (both P < .01). There was no change in cosmesis for most patients.ConclusionIris diaphragm CTR implantation was relatively safe and effective at reducing light and glare sensitivity in eyes with small iris defects.Financial disclosureNo author has a financial or proprietary interest in any material or method mentioned.

PurposeTo evaluate the safety and efficacy of Morcher 96F iris diaphragm implantation to manage small defects of the human iris.SettingJules Stein Eye Institute, UCLA, Los Angeles, California, USA.DesignProspective nonrandomized interventional case series.MethodsDemographic, preoperative, and postoperative data of patients who had implantation of the modified capsular tension ring (CTR) and followed to 1 year were reviewed. Safety measures included loss of corrected distance visual acuity (CDVA), perioperative complications, adverse events, and secondary surgical interventions. Efficacy measures included CDVA with glare, daytime and nighttime glare symptom scores, and subjective cosmesis scores.ResultsSixteen patients had CTR implantation. There was a statistically significant improvement in the median CDVA of 2.5 Snellen lines (P < .01), with 4 patients having minor decreases in CDVA for reasons unrelated to the device. There were no intraoperative complications. Three adverse events were reported: 1 ocular hypertension, 1 postoperative retinal detachment, and 1 25-degree rotation of the CTR. There were 4 secondary surgical interventions. There was a statistically significant improvement in the median CDVA with glare of 8 Snellen lines (P < .01), but 2 patients had a decrease in CDVA with glare for reasons unrelated to the device. There were statistically significant improvements in the median daytime and nighttime glare symptom scores of 5 points and 4 points, respectively (both P < .01). There was no change in cosmesis for most patients.ConclusionIris diaphragm CTR implantation was relatively safe and effective at reducing light and glare sensitivity in eyes with small iris defects.Financial disclosureNo author has a financial or proprietary interest in any material or method mentioned.

Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients., Funding Agencies|Crown Princess Margaretas Foundation for the Visually Impaired||Carmen and Bertil Regners Foundation for Research in Eye Disease||County Council of Ostergotland||Konung Gustav V and Drottning Viktorias Frimurarestiftelse||The Swedish Research Council||Aniridia Norway

Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients., Funding Agencies|Crown Princess Margaretas Foundation for the Visually Impaired||Carmen and Bertil Regners Foundation for Research in Eye Disease||County Council of Ostergotland||Konung Gustav V and Drottning Viktorias Frimurarestiftelse||The Swedish Research Council||Aniridia Norway

PurposeTo report the results of imaging using high-resolution, Fourier domain anterior segment optical coherence tomography (AS-OCT) to evaluate patients with a type 1 Boston Keratoprosthesis (KPro).MethodsWe performed a retrospective comparative study of patients in whom we implanted the Boston KPro. A total of 26 eyes of 23 patients from the Cornea Service at the University of California Davis Eye Center were included. Subjects were evaluated with the Spectralis AS-OCT (Heidelberg Engineering GmbH).ResultsPreoperative diagnoses for KPro surgery included failed corneal transplant (69%), chemical burn (23%), and aniridia (8%). The average age of patients was 63.2 years (range, 17-88 years). Fifty-four percent of the patients were female. The mean duration between the KPro surgery and the acquisition of high-resolution AS-OCT imaging was 35.8 months (range, 2-90 months). The most commonly observed finding was retroprosthetic membrane formation, which we found in 77% of KPro eyes. In 65% of KPro eyes, we identified epithelium behind the front plate, and in 54%, we identified an epithelial lip over the anterior surface of the KPro front plate. In 31% of KPro eyes, we identified periprosthetic cysts, gaps or spaces, and thinning in the corneal carrier graft.ConclusionsFourier domain AS-OCT is a useful noninvasive imaging technique in patients with a KPro and provides the ability to identify changes that are sometimes difficult to appreciate by clinical evaluation. The higher resolution Fourier domain systems may aid in the clinical diagnosis and management of pathology that might not be imaged with instruments of lower resolution. AS-OCT has the potential for monitoring the anatomic stability of an implanted KPro and may also help to monitor for complications. Moreover, high-resolution imaging may enhance our understanding of periprosthetic anatomy.

PurposeTo report the results of imaging using high-resolution, Fourier domain anterior segment optical coherence tomography (AS-OCT) to evaluate patients with a type 1 Boston Keratoprosthesis (KPro).MethodsWe performed a retrospective comparative study of patients in whom we implanted the Boston KPro. A total of 26 eyes of 23 patients from the Cornea Service at the University of California Davis Eye Center were included. Subjects were evaluated with the Spectralis AS-OCT (Heidelberg Engineering GmbH).ResultsPreoperative diagnoses for KPro surgery included failed corneal transplant (69%), chemical burn (23%), and aniridia (8%). The average age of patients was 63.2 years (range, 17-88 years). Fifty-four percent of the patients were female. The mean duration between the KPro surgery and the acquisition of high-resolution AS-OCT imaging was 35.8 months (range, 2-90 months). The most commonly observed finding was retroprosthetic membrane formation, which we found in 77% of KPro eyes. In 65% of KPro eyes, we identified epithelium behind the front plate, and in 54%, we identified an epithelial lip over the anterior surface of the KPro front plate. In 31% of KPro eyes, we identified periprosthetic cysts, gaps or spaces, and thinning in the corneal carrier graft.ConclusionsFourier domain AS-OCT is a useful noninvasive imaging technique in patients with a KPro and provides the ability to identify changes that are sometimes difficult to appreciate by clinical evaluation. The higher resolution Fourier domain systems may aid in the clinical diagnosis and management of pathology that might not be imaged with instruments of lower resolution. AS-OCT has the potential for monitoring the anatomic stability of an implanted KPro and may also help to monitor for complications. Moreover, high-resolution imaging may enhance our understanding of periprosthetic anatomy.

Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients., Funding Agencies|Crown Princess Margaretas Foundation for the Visually Impaired||Carmen and Bertil Regners Foundation for Research in Eye Disease||County Council of Ostergotland||Konung Gustav V and Drottning Viktorias Frimurarestiftelse||The Swedish Research Council||Aniridia Norway

Purpose: The aim of this study is to describe the management of cataract and refractory glaucoma in a case of congenital aniridia (AN)-1. Methods: In an 18-year-old female patient affected by congenital AN, bilateral coloboma of the zonula and lens, cataract and glaucoma, pars plana vitrectomy, cataract extraction and subsequent transcorneal ciliary body argon laser photocoagulation were performed. Results: Five years after laser treatment, the best-corrected visual acuity was 20/50 and the intraocular pressure was stable at 18 mm Hg with topical pharmacological management consisting of timolol 0.5% and latanoprost 0.005%. Conclusions: From our experience, transcorneal ciliary body photocoagulation after cataract extraction and vitrectomy could be a useful technique to manage high ocular pressure in eyes affected by congenital AN. © 2013 S. Karger AG, Basel.

Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients., Funding Agencies|Crown Princess Margaretas Foundation for the Visually Impaired||Carmen and Bertil Regners Foundation for Research in Eye Disease||County Council of Ostergotland||Konung Gustav V and Drottning Viktorias Frimurarestiftelse||The Swedish Research Council||Aniridia Norway

Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients., Funding Agencies|Crown Princess Margaretas Foundation for the Visually Impaired||Carmen and Bertil Regners Foundation for Research in Eye Disease||County Council of Ostergotland||Konung Gustav V and Drottning Viktorias Frimurarestiftelse||The Swedish Research Council||Aniridia Norway

PurposeThe migratory neural crest cell population makes a significant contribution to the anterior segment structures of the eye. Consequently, several anterior segment dysgenesis phenotypes are associated with mutations in genes expressed during neural crest development. The forkhead box D3 (FOXD3) gene encodes a forkhead transcription factor that plays an important role in neural crest specification in vertebrates and therefore may be involved in human eye disease.MethodsWe screened 310 probands with developmental ocular conditions for variations in FOXD3.ResultsSix nonsynonymous FOXD3 variants were identified. Four of these changes, c.47C>T (p.Thr16Met), c.359C>T (p.Pro120Leu), c.517A>C (p.Asn173His), and c.818_829dup (p.Arg273_Gly276dup), affected conserved regions and were observed primarily in probands with aniridia or Peters anomaly; out of these four variants, one, p.Arg273_Gly276dup, was not detected in control populations and two, p.Pro120Leu and p.Asn173His, were statistically enriched in cases with aniridia or Peters anomaly. The p.Arg273_Gly276dup variant was seen in a proband with aniridia as well as two additional unrelated probands affected with anophthalmia or congenital cataracts. The p.Asn173His variant affects Helix 2 of the DNA-binding domain and was observed in two unrelated patients with Peters anomaly or aniridia; in both cases, one parent carried the same allele.ConclusionsFOXD3 variants increase the risk of anterior segment dysgenesis phenotypes in humans. The p.Asn173His mutation affects a residue in the forkhead domain that is 100% conserved among vertebrate orthologs and is predicted to participate in protein-protein interactions. Its phenotypic effects may be modulated by transcriptional cofactors which have yet to be identified.

PurposeThe migratory neural crest cell population makes a significant contribution to the anterior segment structures of the eye. Consequently, several anterior segment dysgenesis phenotypes are associated with mutations in genes expressed during neural crest development. The forkhead box D3 (FOXD3) gene encodes a forkhead transcription factor that plays an important role in neural crest specification in vertebrates and therefore may be involved in human eye disease.MethodsWe screened 310 probands with developmental ocular conditions for variations in FOXD3.ResultsSix nonsynonymous FOXD3 variants were identified. Four of these changes, c.47C>T (p.Thr16Met), c.359C>T (p.Pro120Leu), c.517A>C (p.Asn173His), and c.818_829dup (p.Arg273_Gly276dup), affected conserved regions and were observed primarily in probands with aniridia or Peters anomaly; out of these four variants, one, p.Arg273_Gly276dup, was not detected in control populations and two, p.Pro120Leu and p.Asn173His, were statistically enriched in cases with aniridia or Peters anomaly. The p.Arg273_Gly276dup variant was seen in a proband with aniridia as well as two additional unrelated probands affected with anophthalmia or congenital cataracts. The p.Asn173His variant affects Helix 2 of the DNA-binding domain and was observed in two unrelated patients with Peters anomaly or aniridia; in both cases, one parent carried the same allele.ConclusionsFOXD3 variants increase the risk of anterior segment dysgenesis phenotypes in humans. The p.Asn173His mutation affects a residue in the forkhead domain that is 100% conserved among vertebrate orthologs and is predicted to participate in protein-protein interactions. Its phenotypic effects may be modulated by transcriptional cofactors which have yet to be identified.

Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia).

Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia).

PurposeTo evaluate the asymmetry of the anterior segment phenotype between the two eyes of a patient with Axenfeld-Rieger syndrome (ARS).MethodsThe entire database of a tertiary glaucoma practice was screened for patients with ARS. The medical records of patients with ARS were reviewed. The clinical characteristics of ocular examination of the two eyes of each patient were recorded and compared. Dental and medical information were also reviewed where available. The anterior segment phenotype was tabulated to assess asymmetry. Asymmetric anterior segment characteristics of patients with ARS were compared with reported cases in the literature.ResultsEight patients with ARS were identified from screening of more than 5,000 patients of a tertiary glaucoma practice. All patients had Axenfeld-Rieger anomaly in both eyes except one patient presented with an asymmetric phenotype of the anterior segment with features of Axenfeld-Rieger anomaly in one eye, but aniridia in the other eye. This patient had non-ocular findings including flat midface, hypodontia with lack of an upper incisor, and redundant periumbilical skin, typical for ARS. A heterozygous C>T nucleotide substitution was identified in exon 4 of the pituitary homeobox 2 (PITX2) gene, resulting in the replacement of a glutamine codon (CAG) with a stop codon (TAG) at amino acid position 67. This mutation is denoted c.199C>T at the cDNA level or p.Gln67Stop (or Q67X) at the protein level. Only three cases with asymmetric anterior segment phenotype between the two eyes of a patient with AGS have been reported in the literature.ConclusionsVariability in phenotype may occur between the two eyes of an individual affected by ARS. The current case undermines the advantage of genetic testing to correctly diagnose a rare disease.

PurposeTo evaluate the asymmetry of the anterior segment phenotype between the two eyes of a patient with Axenfeld-Rieger syndrome (ARS).MethodsThe entire database of a tertiary glaucoma practice was screened for patients with ARS. The medical records of patients with ARS were reviewed. The clinical characteristics of ocular examination of the two eyes of each patient were recorded and compared. Dental and medical information were also reviewed where available. The anterior segment phenotype was tabulated to assess asymmetry. Asymmetric anterior segment characteristics of patients with ARS were compared with reported cases in the literature.ResultsEight patients with ARS were identified from screening of more than 5,000 patients of a tertiary glaucoma practice. All patients had Axenfeld-Rieger anomaly in both eyes except one patient presented with an asymmetric phenotype of the anterior segment with features of Axenfeld-Rieger anomaly in one eye, but aniridia in the other eye. This patient had non-ocular findings including flat midface, hypodontia with lack of an upper incisor, and redundant periumbilical skin, typical for ARS. A heterozygous C>T nucleotide substitution was identified in exon 4 of the pituitary homeobox 2 (PITX2) gene, resulting in the replacement of a glutamine codon (CAG) with a stop codon (TAG) at amino acid position 67. This mutation is denoted c.199C>T at the cDNA level or p.Gln67Stop (or Q67X) at the protein level. Only three cases with asymmetric anterior segment phenotype between the two eyes of a patient with AGS have been reported in the literature.ConclusionsVariability in phenotype may occur between the two eyes of an individual affected by ARS. The current case undermines the advantage of genetic testing to correctly diagnose a rare disease.

Purpose: To investigate whether optical coherence tomography (OCT) is helpful in the diagnosis of foveal hypoplasia in children. Methods: Children with albinism and aniridia were examined with Stratus OCT 3 software 4.0.1 (Carl Zeiss Meditec, Dublin, California, USA). A qualitative examination of the macular area was performed with a 128 A-scans/second-single-scan. Macular thickness was measured quantitatively with an automatic fast macular map protocol. The average thickness/volume of the macula was presented as numerical values and as a false colour code in nine modified early treatment of diabetic retinopathy study (ETDRS) areas (A1-A9). A previously collected control group of children was used for comparison. Results: Macular thickness in 13 children with albinism and three children with aniridia was measured with OCT. Comparison with healthy children in the same population was performed. Patients with albinism and aniridia had significantly thicker central macula (A1) and foveola than children in the control group. Conclusion: OCT was found to be useful in the diagnosis of foveal hypoplasia in children.

type:text, To evaluate whether filtering surgery is effective in controlling the intraocular pressure of young aniridic patients with glaucoma, we retrospectively reviewed the charts of aniridic patients with glaucoma under the age of 40 years. We defined a good intraocular pressure control period as the time from surgery until IOP exceeded 20 mm Hg, with or without glaucoma medication. Twenty filtering surgeries (17 trabeculectomies and 3 trabeculectomies with mitomycin C) were performed on 10 eyes in 6 patients for more than 20 years. The mean good intraocular pressure control period after the filtering surgery was 14.6 months (range, 2 to 54 months). Aside from mild choroidal detachment, no other serious complications were encountered. We believe that filtering surgery is efficacious for control of intraocular pressure of young aniridic patients with glaucoma.

To evaluate whether filtering surgery is effective in controlling the intraocular pressure of young aniridic patients with glaucoma, we retrospectively reviewed the charts of aniridic patients with glaucoma under the age of 40 years. We defined a good intraocular pressure control period as the time from surgery until IOP exceeded 20 mm Hg, with or without glaucoma medication. Twenty filtering surgeries (17 trabeculectomies and 3 trabeculectomies with mitomycin C) were performed on 10 eyes in 6 patients for more than 20 years. The mean good intraocular pressure control period after the filtering surgery was 14.6 months (range, 2 to 54 months). Aside from mild choroidal detachment, no other serious complications were encountered. We believe that filtering surgery is efficacious for control of intraocular pressure of young aniridic patients with glaucoma.

To evaluate whether filtering surgery is effective in controlling the intraocular pressure of young aniridic patients with glaucoma, we retrospectively reviewed the charts of aniridic patients with glaucoma under the age of 40 years. We defined a good intraocular pressure control period as the time from surgery until IOP exceeded 20 mm Hg, with or without glaucoma medication. Twenty filtering surgeries (17 trabeculectomies and 3 trabeculectomies with mitomycin C) were performed on 10 eyes in 6 patients for more than 20 years. The mean good intraocular pressure control period after the filtering surgery was 14.6 months (range, 2 to 54 months). Aside from mild choroidal detachment, no other serious complications were encountered. We believe that filtering surgery is efficacious for control of intraocular pressure of young aniridic patients with glaucoma.

To evaluate whether filtering surgery is effective in controlling the intraocular pressure of young aniridic patients with glaucoma, we retrospectively reviewed the charts of aniridic patients with glaucoma under the age of 40 years. We defined a good intraocular pressure control period as the time from surgery until IOP exceeded 20 mm Hg, with or without glaucoma medication. Twenty filtering surgeries (17 trabeculectomies and 3 trabeculectomies with mitomycin C) were performed on 10 eyes in 6 patients for more than 20 years. The mean good intraocular pressure control period after the filtering surgery was 14.6 months (range, 2 to 54 months). Aside from mild choroidal detachment, no other serious complications were encountered. We believe that filtering surgery is efficacious for control of intraocular pressure of young aniridic patients with glaucoma.