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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 m 2 , with 5 of these (10%) having an eGFR < 75 mL/min/1.73 m 2 . 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., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Competing Interests: The authors report no conflicts of interest.

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.

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.

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., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

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.

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.

Background: A new pathophysiologic mechanism has been proposed that indicates that periorbital port-wine birthmarks (PWBs) serve as alternate collateral blood passageways when orbital venous drainage is impaired. The occlusion of such collateral venous channels could, therefore, potentially exacerbate impaired ocular venous flow and trigger the development or worsening of glaucoma in patients with Sturge-Weber syndrome. We investigated to what extent a single application of laser therapy, which occludes only the most superficial portions of a facial PWB, might affect intraocular pressure. Pressures before and after laser treatment were measured to determine pressure difference in 15 patients receiving laser treatment., Observations: The greatest pressure differences were observed in patients with a PWB closest to the eye (P = .02). Posttreatment pressures were significantly decreased, relative to pretreatment pressures, only in patients with a PWB on the eyelid compared with patients with a facial PWB not near the eyes (2.33 vs 0.75 mm Hg; P = .004). No correlation was found between change in pressure and patient age, PWB size, or number of previous treatments., Conclusions: A single laser application to a PWB does not appear to show a clinically relevant change in intraocular pressure. Further study is needed longitudinally in a broad range of patients.

Aim: To determine whether juvenile pilocytic astrocytomas WHO grade I have the potential for spontaneous malignant transformation., Methods: A literature search was performed, cross-referencing juvenile pilocytic astrocytoma, pilocytic astrocytoma, astrocytoma grade I, optic glioma, glioma, low-grade gliomas, polar spongioblastoma, gliocytoma embryonale, and malignant transformation, anaplasia or anaplastic change. Bibliographic PubMed and Google searches were performed, and reference ophthalmology and neuropathology textbooks were utilised., Results: A total of 52 purported cases of malignant transformation were found. Twenty-two of these tumours, however, did not initially match criteria for juvenile pilocytic astrocytoma WHO grade I and were excluded. Six other cases were located within the irradiated field but represented anaplasias developing independently of the primary tumour. The remaining 24 malignancies had all been previously irradiated., Conclusion: Juvenile pilocytic astrocytomas WHO grade I do not undergo spontaneous anaplastic transformation. Malignant transformations have only been demonstrated following radiation therapy. Earlier clinical and histopathological opinions regarding juvenile pilocytic astrocytomas as hamartomatous lesions are reaffirmed.

According to a new, unifying view of the pathogenesis of Sturge-Weber syndrome and related syndromes, signs and symptoms all arise from localized primary venous dysplasia, with effects of venous hypertension transmitted to nearby areas via persisting communicating venous passageways and compensatory collateral venous channels. Port-wine stains result from a vascular disorder rather than a neural disorder. Symptoms depend upon the extent and location of the venous dysplasia. This hypothesis is supported by published data and by original observations and Doppler ultrasonographic studies of orbital venous flow in patients with the Sturge-Weber syndrome. This new understanding of underlying pathophysiology also elucidates the mechanism for tissue hypertrophy. Therapies aimed at obliterating port-wine stains to minimize the cosmetic blemish will reduce collateral venous blood-flow passageways. In some instances, this reduction may worsen blood stasis within the brain and potentially exacerbate neurologic symptoms.

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.

The methods available for studying accommodation are evaluated: Donder's "push-up" method, dynamic retinoscopy, infrared optometry using the Scheiner principle, and wavefront analysis are each discussed with their inherent advantages and limitations. Based on the methodology described, one can also distinguish between causes of accommodative insufficiency. Dioptric insufficiency (accommodative lag) that remains equal at various testing distances from the subject indicates a sensory/neurologic (afferent), defect, whereas accommodative insufficiency changing with distance indicates a mechanical/restrictive (efferent) defect, such as in presbyopia. Determining accommodative insufficiency and the cause can be particularly useful when examining patients with a variety of diseases associated with reduced accommodative ability (e.g., Down syndrome and cerebral palsy) as well as in evaluating the effectiveness of various potentially accommodating intraocular lens designs.

Aims: To evaluate a possible relationship between central corneal thickness (CCT) and optic disc area in patients with primary open-angle glaucoma (POAG)., Methods: Patients with POAG underwent eye examination, optic disc imaging with the Heidelberg Retina Tomograph II (HRT II) and ultrasound corneal pachymetry. Exclusion criteria were prior ocular surgery and low-quality HRT II images (HRT standard deviation (SD) >50). Pearson's correlation coefficients were calculated to assess the associations between CCT and optic disc area., Results: 212 eyes of 137 patients with POAG were examined. In all, 66 (48%) subjects were women, 104 (76%) were Caucasian, 26 (19%) African-American and 7 (5%) other races. 72 eyes remained after excluding those with prior intraocular surgery and low-quality HRT II images. In a univariate analysis of this group, CCT was inversely correlated with optic disc surface area (Pearson's correlation coefficient r = -0.284, p = 0.036, n = 72). Mean (SD) disc area was 2 (0.53) mm(2) (n = 160). Caucasians had significantly smaller discs (p<0.001) than other races (Caucasian 1.9 (0.47) mm(2) (n = 119), African-Americans 2.4 (0.54) mm(2) (n = 31), other races 2.3 (0.45) mm(2) (n = 10))., Conclusion: CCT is inversely correlated to optic disc area. Although thicker corneas have been recognised to cause slight overestimation of true intraocular pressure (IOP), they may also indicate the presence of a substantially smaller, and thus more robust, optic nerve head. People with thinner corneas which slightly underestimate the true IOP may also have larger and more deformable optic discs.

Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of +8.00 to +25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction-corrected vision, produce clinically normal electro-retinograms, and show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.

The necessary settings and parameters were determined for ordinary camera and lens systems to faithfully reproduce out-of-focus and distorted imagery as it falls upon the retina of the human eye. Theoretic considerations of both geometric and physical optics were used to calculate the "relative blur" and distortion produced by refractive error added to ordinary camera lenses as opposed to refractive error in an arbitrary thick-lens optical system bounded by air and fluid (i.e. the eye). In both the camera and the eye, "relative blur" was determined to be directly proportional to dioptric defocus and to aperture size, and effectively independent of the focal length. Distortion of imagery was also found to be independent of the focal length. Photographs corroborate the theoretic findings. A given amount of relative blur, however, appeared somewhat greater when recorded on photographic film than when appreciated by the human eye. The Stiles-Crawford effect, the chromatic aberration of the eye, and neural processing probably each contribute to this difference. Previous investigators have grossly exaggerated blur and distortion in photographs intended to simulate ocular imagery and have drawn misleading conclusions from their results.

Purpose: To report ocular and renal findings specific to the inheritable entity called papillorenal (also known as renal-coloboma) syndrome and relate these to a common cause., Design: Observational case series and genetic study., Participants: Two unrelated probands presenting with absent central retinal vessels and 11 available family members., Testing: Doppler ultrasonographic imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations were performed. In selected cases, indocyanine green angiography, scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements, visual evoked potentials, and magnetic resonance imaging were also performed., Main Outcome Measures: Better defined characteristics of the papillorenal syndrome., Results: Numerous cilioretinal vessels were present with rudimentary or absent central retinal vessels. Superonasal visual field defects, typical for papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in two affected members of one family (with previously unsuspected renal failure in one case), and recurrent pyelonephritis was discovered in four affected members of the other family. No PAX2 mutations were detected., Conclusions: In the papillorenal syndrome, the hereditary absence of central retinal vessels may be missed, leading to confusion with isolated coloboma, low-tension glaucoma, and morning glory anomaly. Greater awareness of this syndrome will avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic counseling. We propose that the papillorenal syndrome is a primary dysgenesis that causes vascular abnormalities predominantly affecting the eye, kidney, and urinary tract, leading to hypoplasia of these structures. The absence of defects in the PAX2 gene in these families suggests that mutations in other genes may also be responsible for this syndrome.

Objective: To demonstrate spontaneous regression of large, clinically symptomatic optic pathway gliomas in patients with and without neurofibromatosis type 1 (NF-1)., Methods: Patient cases were collected through surveys at 2 consecutive annual meetings of the North American Neuro-Ophthalmology Society (NANOS) and through requests on the NANOSNET Internet listserv. Serial documentation of tumor signal and size, using magnetic resonance imaging in 11 patients and computed tomography in 2 patients, was used to evaluate clinically symptomatic optic pathway gliomas. All tumors met radiologic criteria for the diagnosis of glioma and 4 patients had biopsy confirmation of their tumors. In 3 patients, some attempt at therapy had been made many years before regression occurred. In one of these, radiation treatment had been given 19 years before tumor regression, while in another, chemotherapy had been administered 5 years before signal changes in the tumor. In the third patient, minimal surgical debulking was performed 1 year before the tumor began to shrink., Results: Spontaneous tumor shrinkage was noted in 12 patients. Eight patients did not have NF-1. In an additional patient without NF-1, a signal change within the tumor without associated shrinkage was detected. Tumor regression was associated with improvement in visual function in 10 of 13 patients, stability of function in 1, and deterioration in 2., Conclusions: Large, clinically symptomatic optic gliomas may undergo spontaneous regression. Regression was seen in patients with and without NF-1. Regression may manifest either as an overall shrinkage in tumor size, or as a signal change on magnetic resonance imaging. A variable degree of improvement in visual function may accompany regression. The possibility of spontaneous regression of an optic glioma should be considered in the planning of treatment of patients with these tumors.

A boy with a large intracranial glioma of the optic tract and probable neurofibromatosis of the first type was observed for 8 years since the age of 7 years. A series of MR scans was made over this period. A notable decrease of the tumor size was seen on its signals on the MR scans. This was paralleled by an improvement of the vision acuity, color field, and visual field on the involved eye. Patient's grandmother had an intracranial glioma of the optic nerve with a slight but stable decrease of the visual functions. The tumor shape in the grandmother and grandchild is remarkably similar. This finding in the grandmother and stability of her vision decreased from childhood permit us to propose that the tumor did not develop and even regressed with time.

Purpose: To demonstrate that currently available magnetic resonance imaging techniques may verify the absence of the abducens nerve in Duane syndrome., Methods: We performed magnetic resonance imaging in a 36-year-old woman with left Duane syndrome, type 1, using spoiled gradient recalled acquisition in the steady state to obtain high-resolution T1-weighted images through the abducens nerve in its subarachnoid segment. Scans were obtained in the axial plane from the medulla to the midbrain and then reformatted along the plane of the abducens nerve., Result: Unilateral absence of the left abducens nerve was verified using magnetic resonance imaging., Conclusion: The absence of the abducens nerve in Duane syndrome can be verified by modern magnetic resonance imaging techniques.

Purpose: To report the fluorescein angiographic and Doppler ultrasonographic findings in a patient with apparent exclusive ciliary vascular supply of the retina of both eyes., Methods: Case report., Results: The ophthalmoscopic appearance of all arterial vessels emanating from both discs was consistent with a cilioretinal origin. Retinal veins also entered each disc peripherally near the margin, leaving the central part of each disc vacant. Fluorescein angiography showed filling of all arterial vessels simultaneous with the early-phase choroidal background flush bilaterally. Color and power Doppler ultrasonographic imaging demonstrated unequivocally the absence of central retinal vessels within the optic nerves. Both discs were normal in size and excavated with central glial tissue present. The clinical history of monocular, alternating episodes of failing vision with partial resolution and the retinal pigmentation patterns bilaterally were consistent with, though not conclusive for, previous episodes of serous retinal detachments. Coincident systemic anomalies consisted of small kidneys with reduced renal parenchyma discovered on ultrasonography, along with chronic interstitial nephritis., Conclusions: The ophthalmoscopic appearance of optic discs with apparent all-cilioretinal vascular supply has been reported previously, but proof of the absence of central retinal vessels requires Doppler ultrasonographic evidence corroborated by angiographic findings, as exemplified in our case report. We describe the association of this disc anomaly with renal parenchymal disease and its distinction from colobomatous defects.