Urrets-Zavalia syndrome following cataract surgery in dogs: A case series.

Background: In human medicine, Urrets-Zavalia syndrome (UZS) is a well-recognized but uncommon postoperative complication characterized by a fixed dilated pupil, accompanied by iris atrophy and glaucoma. Although it was originally reported in 1963 after penetrating keratoplasty surgery for keratoconus, it has been associated with various ophthalmic procedures such as cataract surgery. The condition has not been previously published in the veterinary literature. Case Description: Three client-owned diabetic dogs that developed UZS´s triad after cataract surgery are described. Despite uneventful phacoemulsification in the six eyes, five developed moderate-to-severe postoperative ocular hypertension. Although intraocular pressure (IOP) spikes were initially controlled, fixed dilated pupils accompanied by iris atrophy and chronic ocular hypertension were seen in the five affected eyes. Aggressive medical and surgical management maintained vision in three of those eyes. In one eye, uncontrolled IOP led to blindness. Conclusion: This is the first published description of UZS in dogs, occurring after phacoemulsification. Although no exact, demonstrable causative element could be determined, we believe that should be considered a triggering condition for this syndrome, as it directly affects the ocular blood flow autoregulation and intrinsic uveal tissue integrity. Until the contrary is proved, diabetes mellitus might be considered as a risk factor for developing this syndrome after cataract surgery in dogs.

A haploscope based binocular pupillometer system to quantify the dynamics of direct and consensual Pupillary Light Reflex.

This study described the development of a haploscope-based pupillometer for the parametrization of the Pupillary Light Reflex (PLR), and its feasibility in a set of 30 healthy subjects (light or dark-colored irides) and five patients diagnosed with Relative Afferent Pupillary Defect (RAPD). Our supplementary aim focused on evaluating the influence of iris colour on the PLR to decide whether a difference in PLR parameters should be anticipated when this system is used across ethnicities. All the participants underwent a customized pupillometry protocol and the generated pupil traces, captured by an eye tracker, were analyzed using exponential fits to derive PLR parameters. A Pupil Response Symmetry (PRS) coefficient was calculated to predict the presence of RAPD. The mean (SD) Initial PD during dilation (3.2 (0.5) mm) and the minimum PD during constriction (2.9 (0.4) mm) in the light iris group had a statistically significant (p < 0.001) higher magnitude compared to the dark iris group. The normal limits of the PRS coefficient ranged from - 0.20 to + 1.07 and all RAPD patients were outside the calculated normal limits. This proposed system, analysis strategies, and the tested metrics showed good short-term repeatability and the potential in detecting pupil abnormalities in neuro-ophthalmic diseases.

Congenital Microcoria: Clinical Features and Molecular Genetics.

Iris integrity is required to regulate both the amount of light reaching the retina and intraocular pressure (IOP), with elevated IOP being a major risk factor for glaucoma. Congenital microcoria (MCOR) is an extremely rare, autosomal dominant disease affecting iris development and hindering both of these functions. It is characterized by absent or underdeveloped dilator muscle fibers and immaturity of the iridocorneal angle-where the aqueous humor is drained-which play a central role in IOP regulation. The dilator muscle anomaly is manifested in pinhole pupils (<2 mm) and thin transilluminable irises, causing both hemeralopia and photoaversion. Axial myopia and juvenile open-angle glaucoma are very frequent (80% and 30% of all cases, respectively). It has been suggested that the immaturity of the chamber angle contributes to glaucoma, and myopia has been ascribed to photoaversion and elevated IOP. Though possible, these mechanisms are insufficient. The disease has been tied to chromosome 13q32.1 structural variations. In addition to compromising iris development, modification of the 13q32.1 architecture could alter signaling pathways for axial ocular length and IOP regulation. Here, we summarize the clinical, histological, and molecular features of this disease, and we discuss the possible etiology of associated anomalies.

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan.

BACKGROUND: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan. METHODS: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease. RESULTS: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys-Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy. CONCLUSIONS: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices. TRIAL REGISTRATION: Not applicable.

Gastrointestinal symptoms as an extended clinical feature of Pierson syndrome: a case report and review of the literature.

BACKGROUND: Pierson syndrome (PS) is a rare autosomal recessive disorder, characterized by congenital nephrotic syndrome and microcoria. Advances in renal replacement therapies have extended the lifespan of patients, whereas the full clinical spectrum of PS in infancy and beyond remains elusive. CASE PRESENTATION: We present the case of a 12-month-old boy with PS, manifesting as the bilateral microcoria and congenital nephrotic syndrome. He was born without asphyxia, and was neurologically intact from birth through the neonatal period. Generalized muscle weakness and hypotonia were recognized from 3 months of age. The infant showed recurrent vomiting at age 5 months of age, and was diagnosed with gastroesophageal reflux and intestinal malrotation. Despite the successful surgical treatment, vomiting persisted and led to severely impaired growth. Tulobuterol treatment was effective in reducing the frequency of vomiting. Targeted sequencing confirmed that he had a compound heterozygous mutation in LAMB2 (NM_002292.3: p.Arg550X and p.Glu1507X). A search of the relevant literature identified 19 patients with severe neuro-muscular phenotypes. Among these, only 8 survived the first 12 months of life, and one had feeding difficulty with similar gastrointestinal problems. CONCLUSIONS: This report demonstrated that severe neurological deficits and gastrointestinal dysfunction may emerge in PS patients after the first few months of life.

Microcoria due to first duplication of 13q32.1 including the GPR180 gene and maternal mosaicism.

Congenital microcoria (MCOR) is an eye anomaly characterized by a pupil with diameter below 2 mm, and is caused by underdevelopment or absence of the dilator muscle of the pupil. Two types have been described: a recessive, syndromic (Pierson syndrome OMIM 609049) and a dominant, isolated form (MCOR syndrome OMIM 156600). Fares-Taie and colleagues described inherited microdeletions in chromosome band 13q32.1 segregating with dominant microcoria in several families. The GPR180 gene is located within the smallest commonly deleted region and encodes a G protein-coupled receptor involved in smooth muscle cells growth. We here describe a patient with isolated, non-syndromic MCOR. The patient presented with a blue iris and small pupils, non-reactive to cycloplegic agents. Her mother had a milder ocular phenotype, namely a blue iris with hypoplastic crypts and mild myopia. We present a detailed clinical examination and follow up. DNA from the index patient was analyzed for the presence of chromosomal imbalances using molecular karyotyping. The genetic test revealed a small duplication of chromosome band 13q32.1. The duplication affected a 289 kb region, encompassing 11 genes including GPR180. Interestingly, the patient displays only MCOR in contrast to patients with the reciprocal deletion who present with MCOR and iridocorneal angle dysgenesis. This genetic anomaly was inherited from the mother who carries the duplication in mosaic form, which should be considered when offering genetic counselling. In summary, we describe the first 13q32.1 duplication encompassing GPR180 associated with MCOR.

Molecular mechanisms determining severity in patients with Pierson syndrome.

Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin ß2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin ß2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.

Urrets-Zavalia Syndrome following cataract surgery in a case of anterior megalophthalmos / Síndrome de Urrets-Zavalia após cirurgia de catarata em um caso de megaloftalmo anterior

ABSTRACT Intraoperative and postoperative cataract surgery in eyes with anterior megalophthalmos are challenging procedures. Herein we describe the case of a 53-year-old male with anterior megalophthalmos who developed unilateral Urrets-Zavalia Syndrome following cataract surgery.

RESUMO O intraoperatório e o pós-operatório de cirurgia de catarata em olhos com megaloftalmo anterior é desafiador. Descrevemos o caso de um homem de 53 anos com megaloftalmo anterior que desenvolveu a Síndrome de Urrets-Zavalia unilateral após cirurgia de catarata.

Urrets-Zavalia Syndrome following cataract surgery in a case of anterior megalophthalmos.

Intraoperative and postoperative cataract surgery in eyes with anterior megalophthalmos are challenging procedures. Herein we describe the case of a 53-year-old male with anterior megalophthalmos who developed unilateral Urrets-Zavalia Syndrome following cataract surgery.

Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ß2 gene.

Pierson syndrome, an autosomal recessive disorder caused by a mutation in laminin ß2 (LAMB2) gene, is characterized by congenital nephrotic syndrome and various ocular abnormalities. The ocular findings in Pierson syndrome are not well understood, because the incidence of this syndrome is very rare. We report ocular findings in a 5-month-old boy with Pierson syndrome with a novel mutation in LAMB2. We performed a pupilloplasty for his microcoria. Ophthalmic examinations after surgery revealed that he had cataract, severe retinal degeneration, and high myopia. Optical coherence tomography showed the collapse of retinal layer structures and a marked decrease of choroidal thickness. Immunohistochemistry and electron microscopy examinations revealed abnormal iris differentiation and thinning or defect of basal membranes. These results suggest that the development of the iris, lens, retina, and choroid are affected in this type of mutation.

Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane.

The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5ß2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases.