Widespread kidney anomalies in children with Down syndrome.

BACKGROUND: Rare autopsy studies have described smaller kidneys as well as urinary tract anomalies in Down syndrome. This observation has never been investigated in vivo and little is known about the possible consequences upon kidney function. Here we wish to confirm whether children with Down syndrome have smaller kidneys and to evaluate their kidney function in vivo. METHODS: This retrospective cohort study enrolled 49 children with Down syndrome, as well as 49 age- and sex-matched controls at the Queen Fabiola Children's University Hospital in Brussels, Belgium. Doppler and kidney ultrasonography, spot urine albumin to creatinine ratio, estimated glomerular filtration rate (eGFR), and anthropometric data were recorded. RESULTS: Kidney size in children with Down syndrome was smaller than age- and sex-matched controls in terms of length (p < 0.001) and volume (p < 0.001). Kidney function based on eGFR was also decreased in Down syndrome compared to historical normal. Twenty-one of the children with Down syndrome (42%) had eGFR < 90 mL/min/1.73 m2, with 5 of these (10%) having an eGFR < 75 mL/min/1.73 m2. In addition, 7 of the children with Down syndrome (14%) had anomalies of the kidney and/or urinary tract that had previously been undiagnosed. CONCLUSIONS: Children with Down syndrome have significantly smaller kidneys than age-matched controls as well as evidence of decreased kidney function. These findings, in addition to well-noted increased kidney and urologic anomalies, highlight the need for universal anatomical and functional assessment of all individuals with Down syndrome. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ciliary Body/Iris Appositioning Producing Mechanical Pupillary Defects in Carotid-Cavernous Sinus Fistula: An Overlooked Pathophysiologic Mechanism.

BACKGROUND: Variable pupillary responses have been described with carotid-cavernous sinus fistulas. These often are associated with a decrease in visual acuity and attributed to retinal ischemia. We propose a novel pathophysiologic mechanism for changes in pupillary reactivity involving anatomic changes secondary to choroidal effusion. METHODS: To demonstrate proof-of-concept, we investigated 2 consecutive patients with carotid-cavernous sinus fistulas and pupillary disturbances using repeated refractions and anterior segment ultrasound biomicroscopy. RESULTS: Ultrasound biomicroscopy demonstrated choroidal thickening and ciliary body effusion with forward rotation of the lens-iris diaphragm altering refraction and mechanically limiting iris movements. CONCLUSIONS: Where there are acute elevations in orbital venous pressure causing ciliary body effusion, changes in visual acuity and pupillary abnormalities can be produced by mechanical effects.

Decreased Corneal Sensation and Subbasal Nerve Density, and Thinned Corneal Epithelium as a Result of 360-Degree Laser Retinopexy.

PURPOSE: To assess the effects of 360-degree laser retinopexy on human corneal subbasal nerve plexus and to investigate correlations among corneal subbasal nerve plexus density, corneal epithelial thickness, and corneal sensitivity. DESIGN: Prospective, observational, nonrandomized study. PARTICIPANTS: A total of 15 eyes of 15 patients who underwent pars plana vitrectomy (PPV) with 360-degree laser retinopexy for retinal detachment (RD) and 15 eyes of 15 patients who underwent PPV for macular hole (MH) without laser treatment. METHODS: Corneal sensation, corneal epithelial thickness, and corneal subbasal nerve plexus density were assessed before surgery and 6 months after surgery via in vivo confocal microscopy, anterior segment optical coherence tomography (AS-OCT), and Cochet-Bonnet esthesiometry (Luneau Ophthalmologie, Paris, France). MAIN OUTCOME MEASURES: Corneal subbasal nerve plexus density, corneal epithelium thickness, and central corneal sensitivity. RESULTS: Compared with baselines values, the mean subbasal nerve density (P < 0.001), mean corneal epithelium thickness (P = 0.006), and mean corneal sensitivity (P < 0.001) in the RD group were significantly decreased 6 months after surgery by 74.3%, 4.7%, and 56.6%, respectively. Conversely, in the MH group there were no significant differences in the mean subbasal nerve density (P = 0.34), mean corneal epithelial thickness (P = 0.19), and mean corneal sensitivity (P = 0.42) between preoperative and 6-month postoperative values (0.7%, 0.4%, and 0.8%, respectively). The postoperative decrease in corneal subbasal nerve density after laser retinopexy was associated with a decrease in corneal epithelium thickness (r(2) = 0.42; P = 0.006) and a decrease in corneal sensitivity (r(2) = 0.48; P = 0.004). The postoperative decrease in corneal sensitivity poorly correlated with the decrease in corneal epithelial thickness (r(2) = 0.24; P = 0.045). Postoperative corneal nerve density decreased as total laser energy increased (r(2) = 0.51; P = 0.002). CONCLUSIONS: Subbasal corneal nerve plexus density decreases after 360-degree laser retinopexy and is accompanied by epithelium thinning and decreased corneal sensation. Surgeons should eschew heavy confluent retinal laser treatment, and corneal sensitivity should be assessed postoperatively to determine whether significant anesthesia has occurred. In such instances, prophylactic measures may be warranted against the development of neurotrophic ulcers.

Brushfield spots and Wölfflin nodules unveiled in dark irides using near-infrared light.

Wölfflin nodules and Brushfield spots were described essentially in light colored irides. The purpose of our study is to determine if these iris features are also present in dark irides, hidden by melanin granules of the anterior leaf of the iris. We examined iris images, taken with standard visible white, as well as with near-infrared light of children with Down syndrome and without. Using white light, Brushfield spots were seen in 21% of children with Down syndrome, and Wölfflin nodules in 12% of controls (p < 0.001), all noted in those with lightly colored irides. Brushfield spots were detected in 67% of children with Down syndrome using near-infrared light compared to 21% using white light (p < 0.001). Wölfflin nodules were detected in 19% of controls using near-infrared light compared to 12% using white light. Peripheral iris thinning was present in 63% of children with Down syndrome but in only 23% of those without (p = 0.001). Contraction furrows were less frequent in children with Down syndrome (16%) compared to controls (74%)(p < 0.001). Near-infrared light unveils Brushfield spots and Wölfflin nodules in dark irides. Clearing this discrepancy should assist in the elucidation of their pathophysiologic origin. A high prevalence of peripheral iris thinning is also present in children with Down syndrome along with a heretofore unreported reduction in iris contraction furrows.

Nonpenetrating external trabeculectomy for congenital glaucoma: a retrospective study.

OBJECTIVE: To evaluate the results of nonpenetrating external trabeculectomy (NPET) for primary congenital glaucoma (CG). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Forty-three eyes of 27 consecutive patients with primary CG. METHODS: Initial intent of NPET with intraoperative conversion to trabeculectomy in cases where aqueous humor outflow was deemed insufficient or where Schlemm's canal appeared to be absent. MAIN OUTCOME MEASURES: Intraocular pressure (IOP). Success was defined as an IOP less than 12.5 mmHg at 1 year after the procedure or later, using adjunctive pressure-lowering topical medications whenever needed. RESULTS: Mean initial measures of IOP were 18.8 mmHg. Of the 43 eyes, a total of 13 required conversion to trabeculectomy: 9 because of insufficient filtration, 3 because of an apparent absence of Schlemm's canal, and 1 because of accidental perforation. Of these 13 eyes that ultimately underwent trabeculectomy, 11 achieved successful IOP control, 3 in association with topical therapy. In 1 eye, a retinal detachment developed, and in 7 eyes, other complications were observed. Among the 30 remaining eyes that underwent NPET, 2 underwent the procedure twice, and 1 eye underwent the procedure 3 times. Postoperative complications were not noted in this NPET-only group. Mean postoperative IOP was 10.8 mmHg, with final IOP controlled in 28 of the 30 eyes (93%; P<0.0001), occasionally after repeat surgeries and in combination with topical therapy. CONCLUSIONS: Nonpenetrating external trabeculectomy may be considered as an initial procedure for some cases of primary CG. It appears to be an alternative to trabeculectomy with fewer risks of postoperative complications.

Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge-Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis).

PURPOSE: To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence. METHODS: Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications. RESULTS: Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion. CONCLUSIONS: Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology-prenatal venous thrombo-occlusion-is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic tissue hypertrophy in these syndromes clarifies physiologic mechanisms for exercise-induced muscle hypertrophy to occur via venous compression and increased capillary transudation.

Cyclodeviation of the retinal vascular arcades: an accessory sign of ocular torsion.

Assessment of ocular torsion via fundus examination is an important tool for diagnosis and management of cyclorotational disorders. The widely used disc-macula relationship for quantification of ocular torsion possesses inherent limitations, which restricts its use in some clinical scenarios. An accessory technique of fundus examination for assessing torsion is hereby proposed using vascular cues. Retinal blood vessels share common guidance signals with ganglion cell axons and are now recognised to follow retinal axonal pathways. Identification of the axis of the retinal vascular arcades can serve as a direct and accessory means to provide additional pertinent information regarding ocular cyclorotations.

Thromboembolism and congenital malformations: from Duane syndrome to thalidomide embryopathy.

OBJECTIVE: To propose a pathophysiologic mechanism to unify a variety of disparate sporadic congenital malformations. METHODS: Inductive and deductive analyses to correlate malformation laterality with asymmetries in thoracic anatomy, critical analysis of malformations with female predominance, and concepts of hydrodynamic pressure gradients in vascular growth were applied to the ensuing development of guiding tissue scaffolds for cellular proliferation, differentiation, and apoptosis. RESULTS: Duane syndrome may develop following a focal vascular insult to the sixth nerve trunk with axonal degeneration, allowing for substitutive innervation from third nerve axons to the lateral rectus muscle. Causative fibrin clots may originate from the venous system and paradoxically migrate through physiological right-to left shunts, or they may arise directly from the heart. Hence, the unilateral, left-sided, and female predominance of Duane syndrome results from the asymmetry in the thoracic anatomy and from thrombosis risk factors. Embolic occlusions may also alter local hemodynamic pressure gradients, leading to the compensatory enlargement and persistence of the fetal vasculature and may dysregulate tissue growth. Within the eye, this results in forms of Peters anomaly, unilateral congenital cataracts, and the morning glory disc anomaly, all in the vascular territory of the carotid arteries that also share a propensity for left-sided involvement in girls. Most aberrant misinnervation phenomena (eg, jaw-winking syndrome, crocodile tear syndrome, Brown syndrome, and congenital fibrosis syndrome) and, by extrapolation, the hypoplasia or dysgenesis of noncephalic anatomical structures (including limbs) may be similarly explained. Such malformations will occur more frequently under thrombogenic conditions, such as those induced by thalidomide. CONCLUSIONS: Fibrin emboli and focal hypoperfusion may explain the development of many sporadic congenital malformations.