Update in Pediatric Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome (PTCS) is a rare condition in children presenting with headache and papilledema from increased intracranial pressure that can cause significant morbidity. This can be idiopathic, also known as idiopathic intracranial hypertension or primary intracranial hypertension, or can be secondary to medications and associated medical conditions. Given the threat to vision, early detection and treatment is needed in all age groups. However, identifying papilledema or pseudopapilledema in children presents unique challenges sometimes as a result of differences between prepubertal and postpubertal children, further elucidating the complex pathophysiology. Management requires brain imaging, lumbar puncture, and frequent eye exams with medical and rarely surgical treatment. Visual outcomes in children are favorable if caught early and management can be prolonged over years. Pediatric PTCS is different from adult PTCS in many ways, and this review will focus on the most updated definitions of the disease, theories of pathophysiology, management, and treatment in the pediatric population.

Axenfeld-Rieger Anomaly and Neuropsychiatric Problems-More than Meets the Eye.

OBJECTIVE: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. CASE STUDY: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. CONCLUSION: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

CUTICULAR DRUSEN: Risk of Geographic Atrophy and Macular Neovascularization.

PURPOSE: Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). METHODS: A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. RESULTS: A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. CONCLUSION: When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

Pigmented paravenous retinochoroidal atrophy associated with Vogt-Koyanagi-Harada disease: a case report.

BACKGROUND: To describe a unique case of pigmented paravenous retinochoroidal atrophy that developed several years after Vogt-Koyanagi-Harada disease. CASE PRESENTATION: A 28-year-old woman presented with gradual vision loss in both eyes and nyctalopia for 2 years. Past medical history was relevant for Vogt-Koyanagi-Harada disease since the age of 19 and positive HLA-DR4. Funduscopic examination revealed perivascular pigmentary clumping and atrophic changes radiating from the optic disks. Spectral domain optical coherence tomography through the macula demonstrated perifoveal outer retinal layers loss with cystic degeneration. Fundus autofluorescence showed zonal areas of hypoautofluorescence corresponding to the areas of atrophy. Full-field electroretinogram identified mildly reduced scotopic and photopic responses. The patient was diagnosed with pigmented paravenous retinochoroidal atrophy. CONCLUSIONS: Pigmented paravenous retinochoroidal atrophy may be acquired after Vogt-Koyanagi-Harada disease. Pathogenesis of pigmented paravenous retinochoroidal atrophy may involve inflammatory-related precursors on a background of genetic predisposition.

Vasa Vasorum Lumen Narrowing in Brain Vascular Hyalinosis in Systemic Hypertension Patients Who Died of Ischemic Stroke.

Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott-Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients.

Biallelic Mutations in GNB3 Cause a Unique Form of Autosomal-Recessive Congenital Stationary Night Blindness.

Congenital stationary night blindness (CSNB) is a heterogeneous group of non-progressive inherited retinal disorders with characteristic electroretinogram (ERG) abnormalities. Riggs and Schubert-Bornschein are subtypes of CSNB and demonstrate distinct ERG features. Riggs CSNB demonstrates selective rod photoreceptor dysfunction and occurs due to mutations in genes encoding proteins involved in rod phototransduction cascade; night blindness is the only symptom and eye examination is otherwise normal. Schubert-Bornschein CSNB is a consequence of impaired signal transmission between the photoreceptors and bipolar cells. Schubert-Bornschein CSNB is subdivided into complete CSNB with an ON bipolar signaling defect and incomplete CSNB with both ON and OFF pathway involvement. Both subtypes are associated with variable degrees of night blindness or photophobia, reduced visual acuity, high myopia, and nystagmus. Whole-exome sequencing of a family screened negative for mutations in genes associated with CSNB identified biallelic mutations in the guanine nucleotide-binding protein subunit beta-3 gene (GNB3). Two siblings were compound heterozygous for a deletion (c.170_172delAGA [p.Lys57del]) and a nonsense mutation (c.1017G>A [p.Trp339(∗)]). The maternal aunt was homozygous for the nonsense mutation (c.1017G>A [p.Trp339(∗)]). Mutational analysis of GNB3 in a cohort of 58 subjects with CSNB identified a sporadic case individual with a homozygous GNB3 mutation (c.200C>T [p.Ser67Phe]). GNB3 encodes the ß subunit of G protein heterotrimer (Gαßγ) and is known to modulate ON bipolar cell signaling and cone transducin function in mice. Affected human subjects showed an unusual CSNB phenotype with variable degrees of ON bipolar dysfunction and reduced cone sensitivity. This unique retinal disorder with dual anomaly in visual processing expands our knowledge about retinal signaling.

Ocular characteristics in a variant microcephalic primordial dwarfism type II.

BACKGROUND: Microcephalic osteodysplastic primordial dwarfism, type II (MOPD II) is a rare disease that is assumed to be caused by a pericentrin (PCNT) gene mutation. Clinical manifestations have been reported in pediatrics and neurology; however, only a few ocular findings have been documented. CASE PRESENTATION: We present three unrelated cases of MOPD II with similar facial features and short stature. Unlike the cases described in the literature, all subjects had normal birth weight and height but their growth was retarded thereafter. In addition to delayed milestones, they have a broad forehead, maxillary protrusion, long peaked nose, high nasal bridge, low-set large ears, extreme reromicrogenia, and normal-sized teeth. These three patients had similar ocular manifestations with the short axial length associated with high hyperopia more than + 9 diopters (D) and macular scarring. The oldest subject was a 20 year-old male without neurological symptoms. One female subject had developed alopecia during the previous 2 years. The other female subject had moyamoya disease, but a genetic study revealed a normal PCNT gene. CONCLUSION: This is the first report of MOPD II focusing on ocular findings, suggesting that macular dystrophy and high hyperopia are the common ocular characteristics of MOPD II. Prompt referral to an ophthalmologist is essential. Although refractive amblyopia can be treated with optical correction, visual prognosis may be poor due to maculopathy.

"Crying without tears" as an early diagnostic sign-post of triple A (Allgrove) syndrome: two case reports.

BACKGROUND: Triple A syndrome (or Allgrove syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency and autonomic/neurological abnormalities. The majority of cases are caused by mutations in the AAAS gene located on chromosome 12q13. However, the clinical picture as well as genetic testing may be complex since symptomatology is variable and mutations cannot be identified in all clinically diagnosed patients. We present two unrelated patients with triple-A syndrome illustrating the importance of alacrima as an early clinical sign. CASE PRESENTATION: A 3.5 year old girl presented with repeated hypoglycaemic myoclonic events. Adrenal insufficiency was diagnosed. In addition, alacrima, obvious since early infancy, was incidentally reported by the mother and finally lead to the clinical diagnosis of triple A syndrome. This was confirmed by positive mutation analysis of the AAAS gene. The second patient, an 8 months old boy was presented because of anisocoria and unilateral optic atrophy. MRI revealed cerebellar vermis hypotrophy. Psychomotor retardation, failure to thrive, and frequent vomiting lead to further diagnostic work-up. Achalasia was diagnosed radiologically. In addition, the mother mentioned absence of tears since birth leading to the clinical diagnosis of triple A syndrome. In contrast to the first cases genetic testing was negative. CONCLUSION: These two patients illustrate the heterogeneity of triple A syndrome in both terms, clinical expression and genetic testing. We particularly aim to stress the importance of alacrima, which should be considered as a red flag symptom. Further differential diagnosis is required in every child affected by alacrima.

Pediatric Pseudotumor Cerebri Syndrome.

Idiopathic intracranial hypertension, otherwise known as primary pseudotumor cerebri syndrome (PTCS), most frequently occurs in obese women of childbearing age. However, children may be affected as well. This review will address recent findings regarding demographics, diagnosis, and treatment of pediatric PTCS. Prepubertal children with primary PTCS have an equal sex distribution and less frequent obesity compared with adult patients. However, female gender and obesity are risk factors for primary PTCS in postpubertal children. Compared with adults, children with PTCS more frequently present with ocular motility deficits and more often have associated medical conditions that increase the risk of developing PTCS. Visual field testing may be unreliable, and the optimal modality to monitor visual function is unknown. MRI shows signs of elevated intracranial pressure (ICP) in children with PTCS similar to that of adults. It has now been established that elevated ICP in children ≤18 years old is greater than 25 cm H20 in nonobese, nonsedated children, and greater than 28 cm H2O in the remainder. Optical coherence tomography (OCT) may be used to distinguish pseudopapilledema from papilledema, monitor response to treatment in preverbal children, and identify patients with PTCS at risk for permanent visual loss. However, the precise role of OCT in the management of pediatric PTCS remains to be determined.

Guidance of Medical Care for Familial Exudative Vitreoretinopathy：Research on Rare and Intractable Diseases, Health and Labour Sciences Research Grants.

Familial exudative vitreoretinopathy is a hereditary insufficiency of retinal vascularture, which manifests a variety of vitreoretinal abnormalities, including nonvascularlized retina, abnormality of retinal vessel growing, dragged retina, retinal folds and total retinal detachment. While causative genes have been identified, cases are often sporadic. Periodic examination is necessary to find recurrence of the disease and late complications, including rhegmatogenous retinal detachment, cataract and glaucoma.

Point-of-care ultrasonography for the identification of 2 children with optic disc drusen mimicking papilledema.

We present 2 cases of asymptomatic patients who were found to have raised and blurred optic discs on physical examination, suggestive of papilledema. Evaluation in the emergency department revealed 2 well-appearing children with normal vital signs and neurologic evaluation results, without symptoms of increased intracranial pressure. Point-of-care ocular ultrasonography was performed on both children, demonstrating calcification at the optic nerve, which is diagnostic of optic disc drusen. Optic disc drusen is caused by the deposition of calcified axonal debris and is often buried within the optic disc in pediatric patients. It can cause some changes in visual acuity and visual fields, but patients who are otherwise asymptomatic can be easily diagnosed through point-of-care ultrasound, thereby sparing patients an aggressive workup if their clinical picture is otherwise reassuring.

Giant dacryocystocele and congenital alacrimia in lacrimo-auriculo-dento-digital syndrome.

The lacrimo-auriculo-dento-digital syndrome, also known as Levy-Hollister syndrome, is a rare multiple congenital dysplasia characterized by malformation of the lacrimal apparatus and by aural, dental, and digital anomalies. Since the first report in 1973, different clinical findings such as urogenital malformations and facial dysmorphism have been described in the affected patients, showing that the phenotypic spectrum of the syndrome is broad. The authors report for the first time an association among giant dacryocystocele, alacrima, and agenesis of the lacrimal puncta in a patient with lacrimo-auriculo-dento-digital syndrome.

[Lysosomal storage diseases - update and new therapeutic options]. / Lysosomale Speichererkrankungen - Update und neue therapeutische Optionen.

Lysosomal storage diseases represent a group of about 50 genetic disorders. The deficiencies of lysosomal and non-lysosomal proteins cause an accumulation of compounds which are normally degraded within the lysosome. There are currently no therapeutic options to cure patients suffering from a lysosomal storage disease. Due to their progressive nature there is considerable morbidity and mortality. Thus, an early treatment to maintain major systemic functions is of utmost importance. While so far only symptomatic therapies are in use, the newly available enzyme replacement therapies offer a real causal approach for selected storage diseases. Many of these disorders are characterised by pathognomonic eye findings. Therefore, the ophthalmological examination provides the opportunity for an early and non-invasive diagnosis and a chance to initiate early treatment. This review is intended to give a survey of the most common lysosomal storage diseases, particularly with regard to ophthalmological changes as well as illustrate new therapeutic options.

Morphological characteristics of parapapillary atrophy and subsequent visual field progression in primary open-angle glaucoma.

BACKGROUND/AIMS: To investigate the associations between the morphological characteristics of beta-zone parapapillary atrophy (ß-zone PPA) and subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG). METHODS: One hundred and twenty-one POAG eyes with ß-zone PPA along with 48 normal eyes with ß-zone PPA were included. ß-zone PPA area was calculated based on the PPA pixel area/optic-disc pixel area ratio and the optical coherence tomography (OCT)-measured disc area. ß-zone PPA margin irregularity was quantified as a function of both area (A) and perimeter (P, calculated as 1/(4πA/P²)). VF progression was defined using standard automated perimetry's guided progression analysis software. RESULTS: Of the 121 POAG eyes, 49 (40.5%) showed VF progression during the 10.1±1.9 years of follow-up. The baseline ß-zone PPA area was similar among the three groups (Progressors, Non-progressors and Controls, p=0.995). However, the ß-zone PPA irregularity index was significantly higher in the Progressors (p<0.001). The cumulative probability of VF progression was greater in the higher PPA irregularity index group (p<0.001, log-rank test). A Cox proportional hazards model showed the significant influences of optic disc haemorrhage (HR: 2.661, p=0.034) and higher baseline PPA irregularity index (HR: 1.455, p=0.007) on subsequent progression. CONCLUSIONS: In POAG eyes, baseline ß-zone PPA margin regularity was significantly associated with subsequent VF progression. Irregular margin of ß-zone PPA might be the mark of vulnerability in the parapapillary area to further glaucomatous damage.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY STUDY OF CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH EARLY-ONSET DRUSEN.

PURPOSE: To report three middle-aged cases with choroidal neovascularization (CNV) associated with early-onset drusen documented with optical coherence tomography angiography (OCTA). METHODS: Three patients with bilateral early-onset drusen were referred to our hospital. Fundus examination, fluorescein angiography, indocyanine green angiography, OCTA, and other multimodal imaging were performed. RESULTS: Case 1 involved a 47-year-old woman who presented with sudden unilateral anorthopia. She had no previous systemic pathologies. Funduscopic examination and fluorescein angiography revealed bilateral large colloid drusen accompanied by unilateral mild subretinal hemorrhage. Indocyanine green angiography revealed CNV, although it was unclear in fluorescein angiography. Optical coherence tomography angiography also showed interconnecting CNV beneath the retinal pigment epithelium. Case 2 involved a 40-year-old woman with membranoproliferative glomerulonephritis Type 3 who presented with unilateral anorthopia. On fluorescein angiography, cuticular drusen secondary to membranoproliferative glomerulonephritis were seen in both eyes. An interconnecting vascular network was revealed with OCTA and indocyanine green angiography indicating Type 1 CNV in the affected eye. Case 3 involved a 47-year-old man without any medical or family history. Predominant large colloid drusen associated with cuticular drusen were seen in both eyes. Unilateral mild serosanguinous changes were accompanied in the macula, where Type 1 CNV was detected with OCTA. CONCLUSION: All our cases with early-onset drusen showed Type 1 CNV that was detected by indocyanine green angiography or OCTA. Optical coherence tomography angiography has a potential to help noninvasively diagnose CNV in the cases of EOD.

Long-term outcomes of "open iridectomy" for secondary anterior chamber epithelial iris cysts.

Epithelial cysts run a high risk of recurrence and conversion to sheet-like ingrowth after surgical intervention. In this retrospective study, we introduced a modified iridectomy for treatment of secondary epithelial iris cysts (EICs) in the anterior chamber. Twenty-nine patients (29 eyes) aged 2-61 years received "open iridectomy" for EICs between April 1995 and July 2019. After viscodissection, most of the cyst wall was cut using a 20-gauge aspiration cutter via a 2.5-mm clear corneal incision. The residue closely adhering to the iris stroma was remained to avoid photophobia and diplopia. At 3 months, best corrected visual acuity was ≥ 20/100 in 55.5% (15/27, except two pediatric patients with poor cooperation) of patients. Among the eight patients suffering partial corneal edema preoperatively, six patients received surgery treatment at 3-6.5 months, and the cornea in the other two patients became transparent after medication. In a mean follow-up of 47.4 months, recurrence occurred in 3 patients at 7, 37, and 118 months, respectively. The percentage of treatment success was 96%, 87%, and 65% at 1, 5, and 10 years, respectively. "Open iridectomy" was effective for EICs, with a minimal invasion, less damage to the corneal endothelium, and a low recurrence rate.

The Axenfeld-Rieger Syndrome Gene FOXC1 Contributes to Left-Right Patterning.

Precise spatiotemporal expression of the Nodal-Lefty-Pitx2 cascade in the lateral plate mesoderm establishes the left-right axis, which provides vital cues for correct organ formation and function. Mutations of one cascade constituent PITX2 and, separately, the Forkhead transcription factor FOXC1 independently cause a multi-system disorder known as Axenfeld-Rieger syndrome (ARS). Since cardiac involvement is an established ARS phenotype and because disrupted left-right patterning can cause congenital heart defects, we investigated in zebrafish whether foxc1 contributes to organ laterality or situs. We demonstrate that CRISPR/Cas9-generated foxc1a and foxc1b mutants exhibit abnormal cardiac looping and that the prevalence of cardiac situs defects is increased in foxc1a-/-; foxc1b-/- homozygotes. Similarly, double homozygotes exhibit isomerism of the liver and pancreas, which are key features of abnormal gut situs. Placement of the asymmetric visceral organs relative to the midline was also perturbed by mRNA overexpression of foxc1a and foxc1b. In addition, an analysis of the left-right patterning components, identified in the lateral plate mesoderm of foxc1 mutants, reduced or abolished the expression of the NODAL antagonist lefty2. Together, these data reveal a novel contribution from foxc1 to left-right patterning, demonstrating that this role is sensitive to foxc1 gene dosage, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld-Rieger syndrome patients.

Association of Drusen Phenotype in Age-Related Macular Degeneration from Human Eye-Bank Eyes to Disease Stage and Cause of Death.

PURPOSE: To stage maculopathy, assess and quantify drusen, determine drusen subtype frequency, and compare subtypes with age-related macular degeneration (AMD) stage and cause of death using an eye-bank model of AMD. DESIGN: Cross-sectional study. PARTICIPANTS: Two thousand ninety-two human eyes from 1067 eye-bank donors, selected from a population at risk for AMD. METHODS: We analyzed donor eye tissue images (2005-2020) using both the 4- and 9-step Minnesota Grading System (MGS), an AMD grading system for eye-bank eyes corresponding to the Age-Related Eye Disease Study classification. The 9-step MGS quantifies total drusen area, hyperpigmentation, and depigmentation. We analyzed reticular pseudodrusen (RPD), basal laminar drusen (BLD), and calcified drusen (CaD) frequency within this population and explored associations with AMD stage, donor age, gender, and cause of death. Statistical analyses were performed using Wilcoxon rank-sum and chi-square tests. Testing encompassed staging eye-bank eyes using MGS analysis. MAIN OUTCOME MEASURES: Drusen subtype frequency associations with AMD stage and cause of death. RESULTS: We detected RPD in 228 (13%), BLD in 131 (7%), and CaD in 84 (5%) of the examined eyes (n = 1777). All subtypes were associated with advanced AMD (RPD: odds ratio [OR], 3.4 [95% confidence interval (CI), 2.5-4.5; P < 0.0001]; BLD: OR, 2.2 [95% CI, 1.5-3.2; P < 0.0001]; and CaD: OR, 39.1 [95% CI, 16.8-91.0; P < 0.0001]). Only the RPD subtype was associated statistically with cardiovascular death when compared with those without cardiovascular death (48% vs. 32%; OR, 2.0 [95% CI, 1.4-2.9]; P = 0.0002). CONCLUSIONS: In a large group of eye-bank eyes selected from a population at risk for AMD and graded using the 4-step and 9-step MGS, RPD, BLD, and especially CaD were associated strongly with advanced AMD. The RPD subtype was associated with a cardiovascular cause of death and may represent an ophthalmologic biomarker for cardiovascular disease.

Ocular and orbital manifestations of the inherited bone marrow failure syndromes: Fanconi anemia and dyskeratosis congenita.

PURPOSE: The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders that share the inability of the bone marrow to produce an adequate number of blood cells. The 4 most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS). All 4 syndromes have been associated with various physical abnormalities. As part of a genotype/phenotype/cancer susceptibility study, we determined the prevalence of ophthalmic manifestations in these 4 syndromes. DESIGN: Cross-sectional study of a patient cohort. PARTICIPANTS: Seventy-five patients with an IBMFS and 121 of their first-degree relatives were seen in the National Eye Institute, National Institutes of Health, from 2001 to 2007. The patient group included 22 with FA, 28 with DC, 19 with DBA, and 6 with SDS. METHODS: Every participant underwent a complete ophthalmic evaluation and digital facial photography with an adhesive paper ruler on the patient's forehead for an internal measure of scale. Interpupillary distance (IPD), inner canthal distance (ICD), outer canthal distance (OCD), palpebral fissure length (PFL), and corneal diameter (CD) were measured. Thirteen of the 22 patients with FA underwent axial length (AL) measurements by A-scan ultrasonography. MAIN OUTCOME MEASURES: Type and prevalence of ophthalmic manifestations. RESULTS: Ninety-five percent of patients with FA had at least 1 abnormal parameter, and 25% of patients had at least 4 abnormal parameters. Eighty-two percent of patients had small palpebral fissures, 69% of patients had simple microphthalmia, 64% of patients had small OCD, 55% of patients had microcornea, 28% of patients had ptosis, and 6% of patients had epicanthal folds. In patients with DC, abnormalities of the lacrimal drainage system (29%) were the most prevalent findings, followed by retinal abnormalities (pigmentary changes, retinal neovascularization, retinal detachment, exudative retinopathy) in 21%, cicatricial entropion with trichiasis and blepharitis in 7% each, and sparse eyelashes and congenital cataract in 3.5% each. No significant ophthalmic abnormalities were seen in patients with DBA or SDS. CONCLUSIONS: Syndrome-specific ocular findings are associated with FA and DC and may antedate diagnosis of the specific syndrome. Early recognition of these abnormalities is important for optimal management.

Primary megalocornea: Case report. / Megalocórnea esencial: relato de caso.

The neonate has a horizontal diameter of the cornea, usually up to 10mm with growth up to 2mm in the first 2 years of life. We report a case of megalocornea, a rare, recessive, X-linked disorder in a 3-month-old child, seeking to review what the medical literature brings information about the condition, as well as diagnostic and follow-up parameters, of its main differential diagnoses.