Unusual onset of Graves' disease associated with thymic hyperplasia in a 5-year-old girl with congenital bilateral clinical anophthalmia: diagnostic and therapeutic challenges.

OBJECTIVES: Graves' disease (GD) is a rare auto-immune disorder in pediatric population. The association between GD and thymic hyperplasia was rarely reported in children. Diagnosis and management of GD are challenging in children. CASE PRESENTATION: This report presents the case of a 5-year-old girl with a personal history of asthma and congenital bilateral isolated clinical anophthalmia who presented with acute congestive heart failure, sinus tachycardia and atypical signs of orbitopathy with edema and erythema of the lower right eyelid and excessive tearing. The diagnosis of GD was based on detecting a suppression of serum TSH level and the presence of high titers of TRAbs. Relapse occurred after 10 months of antithyroid drugs with chief complaints of palpitations, dyspnea and dysphagia. Computed tomography showed heterogeneous anterior mediastinal mass with no invasion into the surrounding tissue. The marked shrinkage of the mass after radioiodine therapy supported the diagnosis of thymic hyperplasia associated with GD. CONCLUSIONS: The presence of clinical anophthalmia may be a confusing factor for the diagnosis of Graves' ophthalmopathy. Recognition of the association between GD and thymic hyperplasia would avoid invasive diagnostic procedures and unnecessary surgical resection. Radioiodine therapy may be used in young children with repeated relapses of GD.

Clinical Characterization of Congenital Anophthalmic and Microphthalmic Cavities in Inidviduals With Craniofacial Anomalies.

OBJECTIVE: Measure the frequency of anophthalmic and microphthalmic patients with craniofacial anomalies (FCAs). DESIGN: Descriptive, cross-sectional, retrospective study. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC-USP). The medical records of patients treated at HRAC from 2000 to 2012 with a diagnosis of congenital anophthalmia or microphthalmia were examined. Patients were excluded for secondary anophthalmia, incomplete medical records, or information that could not be accessed. OUTCOME MEASURES: Frequency of anophthalmia and microphthalmia; the proportions and diagnoses of associated FCAs; impairment of ocular appendages; extracranial or facial anomalies; genetic alterations; and surgical approach. RESULTS: A total of 56 patients had anophthalmia (52.3%), 35 had microphthalmia (32.7%), and 16 patients had both (15%). Individuals with FCAs associated with microphthalmia, anophthalmia, or both totaled 74, corresponding to 69.2%. Anophthalmia was more likely than microphthalmia to be accompanied by FCAs, at 76.4% of patients ( P < 0.05). Cleft lip and palate were the main malformations associated with anophthalmia (23.64%), with microphthalmia (45%), and with both (44.44%). Reconstructive surgery was done in 63.6% of cases. The ocular attachments were compromised in 71% of cases. Extracraniofacial malformations were found in 9.3% of patients. Only 7 records contained karyotypes, and no changes directly related to anophthalmia or microphthalmia were found. CONCLUSION: Anophthalmia is more frequent than microphthalmia and is more often accompanied by FCA. Cleft lip and cleft palate are the most frequent concomitant malformations.

Unilateral Anophthalmia and Congenital Frontal Cranioschisis Associated with Extradural Neuroglial Heterotopia: new Insights into a Possible New Malformative Spectrum.

Background: Neuroglial heterotopia, characterized by mature -neuroglial tissue outside the central nervous system, has not been previously associated with cranioschisis. Case Report: A 4-year-old female patient, with left congenital anophthalmia, had a nasofrontal neuroglial heterotopia protruding through an ossification defect. Discussion: Nasofrontal cranioschisis may be associated with neuroglial heterotopias. The combination of anophthalmia and neuroglial heterotopia, previously described only once in the literature, may be part of a broader malformation spectrum that has not been properly characterized to date.

Congenital Orbital Glial Heterotopia Associated with Clinicopathological Anophthalmia: A Case Report.

Glial heterotopia (GH) is the presence of glial tissue outside the cranial cavity, without communication with the brain. The orbital location usually presents as eyelid swelling, strabismus, and proptosis. This is considered a congenital location that usually presents at birth. Its association with anophthalmia is uncommon. We report the case of a 2-day-old male neonate with left congenital intraorbital lesion presenting with massive proptosis. No eyeball could be seen. Preoperative magnetic resonance imaging disclosed a large and predominantly cystic mass occupying and protruding from the left orbit without intracranial extension. In the operating theatre, a large amount of fluid was aspirated prior to total resection of the mass. Chemical analysis of the fluid was compatible with cerebrospinal fluid. Histologically, the tumor was composed of mature neuroglial tissue and ependymal cells. Despite multiple sections, no choroid plexus or intraocular content was found. The diagnosis of GH with anophthalmia was made.

Language and nonverbal auditory processing in the occipital cortex of individuals who are congenitally blind due to anophthalmia.

Individuals with congenital blindness due to bilateral anophthalmia offer a unique opportunity to examine cross-modal plasticity in the complete absence of any stimulation of the 'visual' pathway even during development in utero. Our previous work has suggested that this complete sensory deafferentation results in different patterns of reorganisation compared with those seen in other early blind populations. Here, we further test the functional specialisation of occipital cortex in six well-studied cases with anophthalmia. Whole brain functional MRI was obtained while these human participants and a group of sighted controls performed two experiments involving phonological and semantic processing of words (verbal experiment) and spatial and identity processing of piano chords (nonverbal experiment). Both experiments were predicted to show a dorsal-ventral difference in activity based on the specific task performed. All tasks evoked activation in occipital cortex in the individuals with anophthalmia but not in the sighted controls. For the verbal experiment, both dorsal and ventral occipital areas were strongly activated by the phonological and semantic tasks in anophthalmia. For the nonverbal experiment, both the spatial and the identity task robustly activated the dorsal occipital area V3a but showed inconsistent activity elsewhere in the occipital lobe. V1 was most strongly activated by the verbal tasks, showing greater activity on the left for the verbal task relative to the nonverbal one. For individual anophthalmic participants, however, activity in V1 was inconsistent across tasks and hemispheres with many participants showing activity levels in the control range, which was not significantly above baseline. Despite the homogeneous nature of the cause of blindness in the anophthalmic group, there remain differences in patterns of activation among the individuals with this condition. Investigation at the case level might further our understanding of how post-natal experiences shape functional reorganisation in deafferented cortex.

The Nasolacrimal Drainage System in 143 Children with the Microphthalmos-Anophthalmos Complex. / Tränenwegsbefunde von 143 Kindern mit Mikrophthalmus-Anophthalmus-Komplex.

BACKGROUND: Report of clinical findings relating to the lacrimal system in congenital clinical anophthalmos and severe blind microphthalmos (MAC-complex patients). METHODS: A retrospective study of the notes of 207 consecutive patients treated surgically at least once with highly hydrophilic self-inflating expanders for MAC between 1998 and 2021. The lacrimal drainage system was always probed and irrigated under general anaesthesia before any other procedure was started. RESULTS: 64 patients were excluded due to possible misdiagnosis because of previous lid or orbit surgery elsewhere or due to missing data. The analysis therefore included 67 girls and 76 boys aged between 1 and 126 months (median age: 5 months). 72 patients presented with unilateral and 42 with bilateral anophthalmos, and 24 had unilateral and 5 bilateral microphthalmos; consequently, 286 orbits (of which, 190 with probable pathology) were available for assessment. In unilateral cases the lacrimal system on the normal side was never affected. On the anophthalmic or microphthalmic side the lacrimal system was normal in 68 orbits only (35.8%). The most frequent finding was canalicular stenosis (91 orbits; 48%). Common canaliculus stenosis was observed in 12 orbits (6.3%) and nasolacrimal duct obstruction in 9 orbits (4.7%). There were four cases of punctal aplasia, but no other anomalies. In unilateral MAC pathologic findings during lacrimal probing were found to be associated with anatomical malformation of the contralateral fellow eye. Only in unilateral anophthalmos there was a significant association with cleft lip and palate, which was not found in the three other groups. CONCLUSIONS: In congenital clinical anophthalmos the lacrimal system is affected in up to 66.5% of cases, mostly due to canalicular stenosis. Even if there is no clear evidence of an embryological connection, this association is certainly not a random finding.

Morphological Changes in the Lacrimal Gland of Anophthalmic Socket in Relation to the Contralateral Normal Eye in Male Wistar Albino Rats: A Histopathology Study.

Purpose: The purpose of the study is to analyze the structural and functional alterations of the lacrimal gland and its tear secretion post-enucleation in Wistar rats.Method: Adult male Wistar rats (n = 15) of 8-week-old were randomly assigned into three groups viz. control, sham, and experimental group (n = 5). Rats of the experimental group were subjected to enucleation of the right eye. Under aseptic surgical conditions, with sterilized forceps, right eyeball of the rats of experimental group was exposed completely out of the socket by applying pressure on the lateral canthus of the eye. Enucleation was then achieved after holding the optic nerve tightly. The surgical procedure was similar in sham group without enucleation. Quantity of tears (Basal and reflex) secreted in both eyes in rats of all groups were measured by using Schirmer's strip, pre- and post-three weeks of enucleation. The lacrimal gland was harvested to analyze histopathological (structural) alterations.Results: Pr- and post-enucleation there was no significant difference observed in the tear volume across the groups. Histopathology of the lacrimal glands from all groups showed preserved lobular architecture with serous acini arranged in lobules, intralobular and interlobular ducts, interstitial fibro collagenous tissue. There was no glandular distortion and atrophy in experimental group.Conclusion: Enucleation do not co-relate or affect the tear volume and lacrimal gland acinar microstructural changes in an anophthalmic socket co-relating to the contralateral normal functional eye.

Lacrimal drainage anomalies in Tessier cleft 3 with unilateral anophthalmos.

Bilateral Tessier cleft types 3 and 4 are rare and commonly involve the lacrimal drainage system owing to their anatomical location. Such clefts commonly present with associated ocular anomalies and include colobomatous eyelids, hypertelorism, microphthalmia, punctal or canalicular agenesis, and nasolacrimal duct obstruction or exstrophy. The current report presents an 18-month-old baby with bilateral Tessier cleft 3 with a unilateral anophthalmos, symmetrical eyelid colobomas, and lacrimal drainage anomalies. The lacrimal anomalies noted include small lacrimal sac with inferior canaliculus on the right side and upper and lower punctal and canalicular agenesis on the left side. Computed tomographic dacryocystography demonstrated unilateral lacrimal sac and bilateral maldevelopment of the bony nasolacrimal duct.

Non-syndromic anophthalmia/microphthalmia can be caused by a PORCN variant inherited in X-linked recessive manner.

Anophthalmia and microphthalmia (A/M) represent severe developmental ocular malformations, corresponding, respectively, to absent eyeball or reduced size of the eye. Both anophthalmia and microphthalmia may occur in isolation or as part of a syndrome. Genetic heterogeneity has been demonstrated, and many genes have been reported to be associated with A/M. The advances in high-throughput sequencing have proven highly effective in defining the molecular basis of A/M. Nevertheless, there are still many patients with unsolved genetic background of the disease, who pose a significant challenge in the molecular diagnostics of A/M. Here we describe a family, with three males affected with the non-syndromic A/M. Whole exome-sequencing performed in Patient 1, revealed the presence of a novel probably pathogenic variant c.734A>G, (p.[Tyr245Cys]) in the PORCN gene. Pedigree analysis and segregation of the identified variant in the family confirmed the X-linked recessive pattern of inheritance. This is the first report of X-linked recessive non-syndromic A/M. Until now, pathogenic variants in the PORCN gene have been identified in the patients with Goltz syndrome, but they were inherited in X-linked dominant mode. The ocular phenotype is the only finding observed in the patients, which allows to exclude the diagnosis of Goltz syndrome.

A rare association of right hemicerebral dysgenesis with congenital anophthalmia in a neonate.

Congenital anophthalmia is rare and can occur due to various etiologies, including genetic defects, teratogenic exposures, and vascular disruptions. We report a rare case of right-sided congenital anophthalmia and hemicerebral dysgenesis in association with ipsilateral hemicerebral vascular dysgenesis in a neonate. Postnatal neuroimaging was conspicuous for a "bare orbit sign." A unilateral cranial neurocristopathy was suspected to be an underlying etiopathology for such a diffuse defect.

Evaluation of Lacrimal Drainage Function in the Anophthalmic Socket by Dacryoscintigraphy.

PURPOSE: To investigate whether impaired lacrimal pump function is a possible cause of discharge in patients wearing an artificial eye compared with the remaining healthy eye. METHODS: Consecutive patients wearing unilateral ocular prosthesis for ≥6 months were included in this retrospective study. Excluded were any deformities of eyelids or nasal passage, socket complications such as entropion, ectropion, ptosis, infection, pyogenic granuloma, contracted socket, obstruction of nasolacrimal duct diagnosed with lacrimal irrigation and a difference greater than 2 mm in terms of protrusion between two eyes detected by Hertel exophthalmometry. Patients were asked to score the levels of tearing and mucopurulent discharge between 0 and 5 to assess lacrimal drainage function subjectively. Furthermore, dacryoscintigraphy was performed to assess the functional status of the lacrimal system objectively. RESULTS: Included were 32 subjects (12 females, 20 males; aged 32.94 ±â€Š17.62, range 13-78). Mean duration of prosthetic wearing 26.41 ±â€Š21.30 (6-72) months. The mean subjective scores of tearing and mucopurulent discharge were 1.56 ±â€Š1.67 and 1.94 ±â€Š1.63, respectively. The rate of functional stenosis was significantly higher in the anophthalmic socket side as compared to the healthy side (P = 0.002). The rates of a presac, preduct, and intraduct obstruction was notes as n = 9, n = 10, n = 1 and n = 0, n = 6, n = 2 in the anophthalmic side and the companion eye, respectively (P = 0.021). CONCLUSION: Compared to paired healthy eyes, the ocular prosthesis exhibited significantly higher rates of functional lacrimal duct obstruction, especially at the presac level. The alterations in orbital volume and tear film composition in addition to reduced corneal reflex blinking may lead to the failure of lacrimal pump function in artificial eyes.

Psychological symptoms in anophthalmic patients wearing ocular prosthesis and related factors.

Anophthalmic patients not only cause obvious functional deficits and facial deformities, but lead to poor psychological outcomes, although prosthesis wearing can offer improvements in psychological well-being to some extent. The study aimed to comprehensively evaluate the psychological symptoms and analyze related factors in anophthalmic patients wearing ocular prosthesis.Total of 150 anophthalmic patients and 120 control subjects were included in this cross-sectional study. Baseline characteristics survey and the symptom checklist-90 scale were completed by all participants to assess the psychological symptoms and analyze their related factors by multivariate analysis.The anophthalmic patients exhibited the increased levels of somatization, depression, anxiety, and hostility compared with control subjects. The most prominent symptom was hostility with the median score of 1.20. Female patients presented with higher somatization, depression, anxiety, and hostility. Marital status single was positively associated with depression, anxiety, and hostility symptoms. Lower education and cause of enucleation were related to higher levels of hostility.Anophthalmic patients wearing ocular prosthesis presented with more prominent hostility and somatization besides its higher depression and anxiety symptoms. The findings suggest that for female single anophthalmic patients with low education, especially caused by trauma, timely psychological assessment and intervention should be provided to avoid undesirable consequences.

Identification of a possible association of JAK2 in development of microphthalmia, anophthalmia, and coloboma (MAC) complex in a child with 9p deletion and duplication.

BACKGROUND: Microphthalmia, anophthalmia, coloboma (MAC) complex is a spectrum of ocular abnormalities that occur in isolation or as part of a syndrome. Genetic abnormalities have been shown to account for 80% of cases in bilateral anophthalmia or severe microphthalmia, where 25-30% were attributed to chromosomal defects in this subset of MAC patients. To date, chromosome 9 short arm (9p) abnormalities have not been shown to associate with development of MAC. PURPOSE: To report a case of MAC spectrum disorder that is related to 9p deletion and duplication. MATERIALS AND METHODS: A child who exhibited signs of MAC was evaluated retrospectively. Genetic analysis with comparative genomic hybridization (CGH) and a family pedigree was obtained from the proband. RESULTS: A 3-year-old girl with a history of an atrial septal defect, a horseshoe kidney and global developmental delay was presented. Ophthalmic examination revealed bilateral iris coloboma, bilateral choroidal-retinal coloboma, and left-sided microphthalmia. Subsequent oligonucleotide-based array CGH revealed two different sites of duplication and deletion on 9p (9p24.3 (209020_1143516)x1, 9p24.3p24.1 (1158662_6395264)x3). CONCLUSION: We present the first case of MAC spectrum disorder that is related to 9p deletion and duplication. The link between the associated genetic abnormality and the phenotypic features is yet to be established. Duplication of JAK2 gene, which is within the same region of abnormalities, may have potentiated the development of MAC spectrum disease.

Lacrimal drainage system anomalies in microphthalmia anophthalmia coloboma complex.

Purpose: To study the prevalence and types of lacrimal drainage system (LDS) anomalies inchildren with congenital microphthalmia anophthalmia coloboma (MAC) complex.Methods: This is a prospective, consecutive, non-comparative, case series of LDS anomalies in 31 children presenting with MAC complex. Previously untreated children with MAC complex, enrolled for socket surface and volume expansion during the study period from January 2017 to April 2018 were included.Results: Thirty-one patients with MAC complex were evaluated for LDS anomalies. Incidence of LDS anomalies in children presenting with MAC complex was 68% (42 of 62 lacrimal systems evaluated). Mean age of the patients at the time of examination under anaesthesia was 27 ± 25 (median 15 months, range 3-108 months). Proximal bicanalicular block (BCB) was the commonest LDS anomaly, noted in 15 (48%) cases. In patients with unilateral ocular disease (n = 20), LDS was affected in 14 (70%) patients and in 9 (45%) patients ipsilateral side LDS was affected. In patients with bilateral ocular disease (n = 11), LDS was affected in 7 (64%) patients. Three patients with unilateral anophthalmos (25%) had an ipsilateral upper canalicular block and contralateral nasolacrimal duct obstruction, of which one patient had a single canalicular wall hypoplasia along with CNLDO. No patient had punctal anomalies.Conclusions: LDS anomalies are seen in nearly two-thirds (68%) of children with MAC complex. The lacrimal drainage system anomaly is not limited to the side of the MAC complex. Commonest LDS anomaly is proximal bicanalicular blocks while punctal anomalies are unusual.

Indications for Pediatric Ocular Prosthesis Fitting at a Referral Center in the Middle East.

Trauma is the major reason for globe loss in adults; however, there are less data regarding the causes for globe loss in children. We reviewed the underlying diagnoses of children who underwent ocular prosthesis fitting over a 1-year period at a referral eye hospital in the Middle East and found retinoblastoma, trauma, and congenital microphthalmia or anophthalmia to be the most common diagnoses, respectively. Enucleation and evisceration were the most common procedures and were exclusively performed for retinoblastoma and trauma, respectively. Ocular morbidity from the most common diagnoses related to pediatric globe loss in the region could be decreased by improved family education, safety precautions, and genetic counseling.

Management of congenital microphthalmos and anophthalmos with orbital cyst.

PURPOSE: To study the effects of an individualized treatment approach to children with congenital microphthalmos and anophthalmos. METHODS: Patients with congenital microphthalmos or anopthalmos with orbital cysts who were referred to Beijing Tongren Hospital between July 2009 and July 2017 were included in this retrospective case series study. For patients ≤6 years of age, the cyst was retained to promote orbital development unless a prosthesis could not be fitted at all or disproportionate orbital growth was detected. Hydrogel orbit expanders were implanted initially if orbital volume was poor. For patients >6 years of age, the cyst was removed if it caused cosmetic problems or unsatisfactory prosthesis fitting. Eyelid procedures were performed after puberty to improve appearance. RESULTS: The study included 26 orbits of 24 patients. Of the 14 patients ≤6 years, 3 underwent cyst excision, 8 were treated with conformers only, and 3 had hydrogel orbit expander implantation initially. Of the 10 patients >6 years, 1 had the cyst removed, 5 had eyelid surgeries without removing the cyst, 3 wore an artificial eye without any surgery, and 1 used no prosthesis. During the follow-up period (range, 6 months to 8 years), 23 patients had a good cosmetic outcome and were eventually able to retain an ocular prosthesis; 1 patient could not wear prostheses but refused further treatment. No procedure-related complications were noted. CONCLUSIONS: The individualized treatment of congenital microphthalmos and anophthalmos with orbital cysts depends on the patient's age at presentation, the growth pattern of the cyst, and the volume of the affected orbit.

Bipedicle Dermis Fat Graft for Orbital Volume Augmentation and Repair of Lower Eyelid Retraction in an Anophthalmic Socket With Prior Orbital Implant Placement.

Buphthalmos can create treatment challenges for socket rehabilitation following enucleation due to compression atrophy and mechanical stretching of adnexal tissues. The authors report a case demonstrating a surgical technique for simultaneous volume augmentation of the anophthalmic socket, expansion of the conjunctival fornix, and repair of lower eyelid retraction in a patient with history of buphthalmos and a previously placed 22 mm orbital implant at the time of enucleation. The authors utilized a single-stage, bipedicle dermis fat graft. Postoperatively, the patient demonstrated improvement in lower eyelid position, lower eyelid volume, improved prosthesis fit, improved three-dimensional projection of the ocular prosthesis, and an improvement in the superior sulcus deformity. Bipedicle dermis fat grafts are an option for surgical rehabilitation of the anophthalmic socket when orbital volume deficiency, conjunctival fornix contracture, and eyelid retraction are present and an adequately sized orbital implant has previously been placed.

Reconstruction of Contracted Eye Socket With Autogenic Dermal Sphere Connected to Epidermis.

BACKGROUND: Because of the deficiency of blood circulation and soft tissue, reconstruction of the eye socket for severe conjunctival sac stenosis in anophthalmic patients is very difficult. In this article, the authors report an innovative technique for conducting a 1-stage operation to reconstruct the contracted eye socket with an autogenic dermal sphere connected to the epidermis (ADSE). METHODS: Five patients, each having a single severely contracted eye socket and conjunctival sac, were included in this study. An ADSE was transplanted into the contracted eye socket and conjunctival sac. After the operation, several observation indexes were evaluated, such as the survival and stability of implanted autologous tissue, the improvement of the contracted eye socket, and the degree of patients' satisfaction with their appearance. RESULTS: All of the implanted epidermal and dermal tissues survived well after 6 months' observation. Although somewhat absorbed, the transplanted dermal ball was plump in the eye socket, and the epithelial tissues merged well with the residual conjunctival epithelium. Moreover, the transplanted epidermis assumed a mucosal appearance in 4 of 5 patients. After reconstruction of the eye socket, the size of the conjunctival sac and depth of the eye socket were corrected sufficiently for patients to wear an ocular prosthesis. CONCLUSIONS: The implantation of an ADSE can reconstruct a severely contracted eye socket in anophthalmic patients. Because of the high survival rate and limited absorption ratio, this 1-stage operation satisfied both patients and their ophthalmologists.