Multiple Ocular Abnormalities Research Articles

TREX1 Mutations in Aicardi–Goutières Syndrome with Congenital Glaucoma

TREX1 Mutations in Aicardi–Goutières Syndrome with Congenital Glaucoma

Microphthalmia, aphakia and agenesis of the optic chiasm and tract in a wild fox squirrel (Sciurusniger)

We describe gross and histopathological features of multiple ocular and neuro-ophthalmic abnormalities in a fox squirrel (Sciurus niger). Ophthalmic findings included severe bilateral microphthalmos, with the right eye more affected than the left. Histopathology confirmed severe microphthalmia, aphakia, disorganized retinal tissue and small optic nerves, as well as agenesis of the optic chiasm and optic tract. This combination of neuro-ophthalmic abnormalities has not been previously described in wild animals.

Ophthalmologic manifestations of organoid nevus syndrome: A series of 13 cases

BackgroundThe organoid nevus syndrome is a rare neurocutaneous syndrome typified by cutaneous sebaceous nevus, seizures and epibulbar choristomas. The condition is associated with multiple ocular abnormalities. Herein, the authors aim to study and report the ophthalmic features of cases diagnosed with organoid nevus syndrome. MethodsThe authors retrospectively evaluated the records of patients with the organoid nevus syndrome who had presented to a tertiary care eye hospital in northern India. The ocular features were studied and entered in MS excel and the data were evaluated. ResultsData of 13 patients with the organoid nevus syndrome were found. All 13 patients had cutaneous features in the form of Sebaceous nevus of Jadasson, 8 patients had alopecia of the scalp area, 2 had history seizures and 10 had arachnoid cysts on neuroimaging of the head. All 13 patients had a complex choristoma involving the ocular surface. ConclusionsWe conclude that the most common ophthalmologic features associated with organoid nevus are complex choristoma of the bulbar surface, scleral coat calcification and upper eyelid coloboma.

Simultaneous Management of Retinal Detachment and Aphakia with Pars Plana Vitrectomy, Silicone Oil Tamponade and Retropupillary Iris-Claw Intraocular Lens Implantation in These Cases.

Marfan Syndrome is an autosomal dominant disease with multiple ocular abnormalities including ectopia lentis and a high incidence of rhegmatogenous retinal detachment (RRD). The management of RRD may be challenging in cases of aphakic patients with Marfan. To report on the management of four cases of simultaneous RRD and aphakia with vitrectomy, silicone oil tamponade, and retropupillary iris-claw intraocular lens (IOL) implantation in patients with Marfan that have been operated at the Jules-Gonin Eye Hospital between 2019 and 2020. Ages at presentation were 20, 30, 32, and 31 years, respectively. All patients had a history of extraction of a dislocated lens. None of the patients had a previous posterior vitrectomy. Two patients had records of previous measurements for IOL calculation by optical biometry (IOL Master, Carl Zeiss Meditec AG, Jena, Germany) about 1 year prior to the RRD development. In two cases, measurements for IOL calculation by optical biometry were based on the contralateral eye. All patients underwent 23 G vitrectomy, peripheral iridotomy, and retropupillary iris-claw IOL. No intraoperative complications were encountered. All patients had silicone oil tamponade, one of which required heavy silicone oil. Silicone oil was removed 3 months following primary surgery. Minimum follow-up was 1 year. The single surgery anatomic success rate was 100%. All patients had visual acuity of at least 0.8 at the last follow-up (1.25, 1.0, 0.8, and 0.8 respectively). The targeted refractive results were accurately achieved in all four cases postoperatively. One patient presented ocular hypertension 2 weeks after surgery due to presumed steroid response and was managed conservatively. None of the patients had silicone oil migration into the anterior chamber. Retropupillary iris-claw IOL implantation in cases of RRD and aphakia creates a barrier to tamponades from the posterior segment, effectively preventing them from entering the anterior segment of the eye. Therefore, the management of aphakia and retinal detachment with simultaneous vitrectomy and a retropupillary iris-claw IOL may be a successful strategy in reducing postoperative complications in patients with Marfan syndrome.

Detection of a novel PAX6 variant in a Chinese family with multiple ocular abnormalities

BackgroundAniridia is a congenital, panocular disease that can affect the cornea, anterior chamber angle, iris, lens, retina and optic nerve. PAX6 loss-of-function variants are the most common cause of aniridia, and variants throughout the gene have been linked to a range of ophthalmic abnormalities. Furthermore, particular variants at a given site in PAX6 lead to distinct phenotypes. This study aimed to characterize genetic variants associated with congenital aniridia in a Chinese family.MethodsThe proband and family underwent ophthalmologic examinations. DNA was sampled from the peripheral blood of all 6 individuals, and whole-exome sequencing was performed. Sanger sequencing was used to verify the variant in this family members.ResultsA novel variant (c.114_119delinsAATTTCC: p.Pro39llefsTer17) in the PAX6 gene was identified in subjects II-1, III-1 and III-2, who exhibited complete aniridia and cataracts. The proband and the proband’s brother also had glaucoma, high myopia, and foveal hypoplasia.ConclusionsWe identified that a novel PAX6 frameshift heterozygous deletion variant is the predominant cause of aniridia in this Chinese family.Trial registrationWe did not perform any health-related interventions for the participants.

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier.

Despite flaviviruses remaining the leading cause of systemic human infections worldwide, ocular manifestations of these mosquito-transmitted viruses are considered relatively uncommon in part due to under-reporting. However, recent outbreaks of Zika virus (ZIKV) implicated in causing multiple ocular abnormalities, such as conjunctivitis, retinal hemorrhages, chorioretinal atrophy, posterior uveitis, optic neuritis, and maculopathies, has rejuvenated a significant interest in understanding the pathogenesis of flaviviruses, including ZIKV, in the eye. In this review, first, we summarize the current knowledge of the major flaviviruses (Dengue, West Nile, Yellow Fever, and Japanese Encephalitis) reported to cause ocular manifestations in humans with emphasis on recent ZIKV outbreaks. Second, being an immune privilege organ, the eye is protected from systemic infections by the presence of blood-retinal barriers (BRB). Hence, we discuss how flaviviruses modulate retinal innate response and breach the protective BRB to cause ocular or retinal pathology. Finally, we describe recently identified infection signatures of ZIKV and discuss whether these system biology-predicted genes or signaling pathways (e.g., cellular metabolism) could contribute to the pathogenesis of ocular manifestations and assist in the development of ocular antiviral therapies against ZIKV and other flaviviruses.

Validity of the Red Reflex Exam in the Newborn Eye Screening Test Cohort.

The validity of the red reflex exam has yet to be tested against new methods of wide-angle imaging that may improve early detection of neonatal ocular pathology. The authors aimed to determine the validity of the pediatrician's red reflex exam using 130° wide-angle external and fundus digital imaging as a gold standard. This was a prospective cohort study of 194 healthy, term newborns enrolled in the Newborn Eye Screening Test study at Lucile Packard Children's Hospital from July 25, 2013, to July 25, 2014. Red reflex screening was performed by a pediatrician in the newborn nursery and wide-angle fundus digital imaging was performed by a neonatal intensive care unit-certified nurse. The main outcome measure was the validity of the pediatrician's red reflex exam (unweighted kappa [κ] statistic, sensitivity, specificity). Compared to no subjects with abnormal red reflex exams reported in the pediatrician's notes, 49 subjects demonstrated one or multiple ocular abnormalities on 130° wide-angle fundus imaging (κ = 0.00). The pediatrician's red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%-7.3%) and specificity of 100.0% (95% CI, 97.5%-100.0%) for the detection of ocular abnormalities. This study demonstrates the ability of wide-angle fundus imaging to detect fundus abnormalities not otherwise identified by standard newborn red reflex screening prior to hospital discharge. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:103-110.].

Altered whole-brain connectivity in albinism.

Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc.

A Survey of ocular abnormalities in Miniature Horses

To determine the incidence of ocular abnormalities in miniature horses. Descriptive study. Fifty-three miniature horses. Ophthalmic examinations were performed using diffuse and focal illumination, slit-lamp biomicroscopy and indirect ophthalmoscopy. Coat color, mane and tail color, age and gender were recorded with results of ophthalmic examination. Ocular abnormalities detected most frequently consisted of cysts arising from the posterior iris, ciliary body, and peripheral retina, curvilinear streaks of retinal pigmented epithelium extending from the peripheral temporal retina, and retinal dysplasia (folds). One miniature horse also had multiple ocular abnormalities (cornea globosa, goniosynechiae, decreased or absent and pupillary light reflexes, miotic and dyscoric pupils, iris hypoplasia, and epinuclear cataract). Ocular abnormalities were observed in horses that had a flaxen or white mane and tail color and a chocolate coat color. Abnormal ocular phenotype detected in eyes of Miniature Horses was similar to multiple congenital and hereditary ocular abnormalities reported in the Rocky Mountain Horse. Phenotypic ocular developmental abnormalities and coat, mane and tail color were most compatible with a heterozygous or homozygous effect of the Silver Dapple locus.

CASE REPORT: Unilateral eyelid lesion and ophthalmologic findings in an aardvark (Orycteropus afer): case report and literature review

To summarize the medical knowledge surrounding aardvarks to date, to describe the ophthalmic examination of a specimen with a chronic history of an upper eyelid lesion, of an assumed blind left eye, and to detail the anesthesia procedure performed. A 23-year-old aardvark was examined under general anesthesia and multiple ocular abnormalities were detected in the left eye (globe deviation, corneal opacities, iridodonesis, and aphakia). A thickening of the palpebral conjunctiva affecting the medial upper eyelid with erosion of the normal eyelid margin anatomy was identified. The adnexal lesion was resected by a wedge resection and histopathology was performed. Suture breakdown 3 days postoperatively required a second surgery, where buried sutures were used. The surgical techniques and postoperative care are discussed. The histopathology revealed mucosal hyperplasia and moderate neutrophilic and lymphoplasmacytic blepharitis. No causal organisms were identified. Following initial wound dehiscence and a modified surgical technique, the upper eyelid healed without complication and retained complete function. The eyelid lesion involved a benign inflammatory and hyperplastic pathology of unknown etiology. Adjusting routine ophthalmic surgical techniques to wildlife and zoo animals can be challenging and complicated. It is important to understand the nature of the animals being managed, their circadian cycle, and habitat, to adjust and individualize the surgical approach, instrumentation, suture material, and perioperative treatment.

Multiple kongenitale okuläre Anomalien beim Rocky Mountain Horse und beim Kentucky Mountain Saddle Horse in Europa

The study describes the prevalence of multiple congenital ocular abnormalities (MCOA) in Rocky Mountain Horses and Kentucky Moutain Saddle Horses in Europe. Materials and methods: 35 RMH und KMSH were examined between 1999 and 2010. Their coat color were chocolate (24), seal brown (7), and one each of bay, black, chestnut and palomino. Ciliary body cysts (CBC) were found in 17/35 hor- ses. Two (2/35) horses had multiple congenital ocular abnormalities consistent with anterior segment dysgenesis (ASD). None of the seal brown, black or bay horses had ocular abnormalities, while 18/24 chocolate horses had lesions. One chestnut mare had also bilateral CBC. Fourteen horses (40%) were unaffected. While the prevalence of multiple ocular abnormalities appears to be lower in Europe than in the US, the prevalence of ciliary body cysts is almost the same. Prior to breeding, RMH und KMSH should be carefully examined for the presence of CBC and MCOA. Keywords: Mountain horse, eye, congenital anomaly, anterior segment dysgenesis

Multiple Ocular Abnormalities Associated with Trisomy 4p

Ocular features associated with trisomy 4p have rarely been described. The authors have experienced multiple ocular abnormalities (bilateral cataracts, posterior synechiae, and posterior segment changes) associated with this chromosomal abnormality. It was presumed that these intraocular findings might be associated with the previous inflammatory process. In the current case, the patient recovered some useful vision after surgical removal of cataracts and intraocular lens implantations in both eyes. A detailed ophthalmic examination for patients with the autosomal imbalance is recom-mended.

Disorders of pigmentation in infants and children

Vitiligo is an autoimmune disorder characterized by ivory-white patches secondary to melanocyte destruction. The disease is inherited as autosomal dominant with variable penetrance and is estimated to affect 1–2% of the population.1 Thirty percent of patients have either a positive family history of vitiligo or a history of halo nevi or premature hair graying.2,3 Vitiligo usually affects young adults, with 50% of cases occurring before the age of 20 and 25% before the age of 8 years.4 The disease is uncommon in infancy. In most cases, symmetrical lesions develop on sunexposed areas like the dorsa of hands, the face, and neck.5 Other favored sites include body folds like the axilla and groin and body orifices such as the mouth, nose, umbilicus, genitalia, and anus. Vitiligo lesions can also arise over bony prominences like the elbows and knees. Lesions are usually variable in size and shape and consist of well-defined depigmented macules and patches. Loss of pigment may not be apparent in fairskinned individuals but may be disfiguring in blacks. Vitiligo can appear at sites of trauma or sunburn (Koebner’s phenomenon). A variant of vitiligo is the segmental type, which consists of asymmetrically distributed, depigmented macules confined to one nerve segment (Fig 1). This form is more common in children and is highly associated with autoimmune disorders and premature graying.6 Associations There is a 10–20% incidence of vitiligo in endocrine autoimmune disorders like Hashimoto’s thyroiditis, diabetes mellitus, polyendocrine deficiencies, and parathyroid abnormalities.7 In addition, patients with lymphoma, leukemia, myasthenia gravis, scleroderma, and alopecia areata have a higher incidence of vitiligo. It is estimated that 20% of patients with malignant melanoma have vitiligo, and its presence is a poor prognostic factor.2,8 Vitiligo patients are prone to multiple ocular abnormalities, including discrete depigmentation in the choroid and retinal pigment epithelium, chorioretinitis, uveitis, and iritis. The Vogt-Koyanagi-Harada syndrome is a rare disorder characterized by bilateral uveitis, alopecia, vitiligo, deafness, and possible meningeal irritation.9 The Alezzandrini syndrome consists of bilateral deafness with unilateral degenerative retinitis, unilateral vitiligo and poliosis.10 The differential diagnosis of vitiligo includes postinflammatory hypopigmentation, pityriasis alba, tinea versicolor, albinism, and the ash leaf macule of tuberous sclerosis.

A novel hereditary developmental vitreoretinopathy with multiple ocular abnormalities localizing to a 5-cM region of chromosome 5q13-q14

Background To undertake a clinical and molecular analysis of a previously unpublished kindred with a phenotypically distinct vitreoretinopathy characterized by associated ocular developmental abnormalities. Design Family genetic study. Participants A total of 23 members, both affected and unaffected, of 1 kindred with vitreoretinopathy. Method Individuals within the kindred were examined clinically and blood samples taken for DNA analysis. Genetic analysis was performed for the proximal region of chromosome 5q by means of polymerase chain reaction (PCR). Main outcome measures Detection of vitreoretinopathy and associated abnormalities. Results This novel, hereditary vitreoretinopathy, showing the classic features of vitreous pathology and early-onset retinal detachments, was associated with a variety of ocular developmental abnormalities, including posterior embryotoxon, congenital glaucoma, iris hypoplasia, congenital cataract, ectopia lentis, microphthalmia, and persistent hyperplastic primary vitreous. There were no associated systemic features. Genetic mapping with markers from the proximal region of 5q13-q14 showed linkage to a 5-cM region between the markers D5S626 and D5S2103. Conclusions The 5-cM region is within that implicated in the etiology of both Wagner and erosive vitreoretinopathies. This suggests that this novel condition may be allelic, refines the genetic mapping for vitreoretinopathies that map to 5q13-q14, and implicates a gene important not only in vitreous production but also in early ocular development.

Congenital ocular abnormalities of Rocky Mountain Horses.

OBJECTIVE: To determine the incidence and describe ocular abnormalities in a cross-section of the population of Rocky Mountain Horses. Design: Prospective study. Animals: Five-hundred and fourteen Rocky Mountain Horses. Procedure: Ophthalmic examinations were performed using a slit-lamp biomicroscope and an indirect ophthalmoscope. Intraocular pressures were measured by applanation tonometry. Eyes from six horses were obtained for histologic examination. RESULTS: Cysts of the posterior iris, ciliary body, and peripheral retina were detected most frequently (249 horses), and were always located temporally. Curvilinear streaks of retinal pigmented epithelium extending from the peripheral temporal retina marked the boundary of previous retinal detachment in 189 horses. Retinal dysplasia was detected in 125 horses. Multiple ocular anomalies were evident in 71 horses and were always bilateral and symmetrical. Affected eyes had a large, clear cornea that protruded excessively and had an apparent short radius of curvature, a deep anterior chamber, miotic and dyscoric pupil, and iris hypoplasia. Pupillary light responses were decreased or absent and pupils failed to dilate after repeated instillation of mydriatic drugs in horses with multiple ocular anomalies. Less frequently encountered abnormalities included peripheral iridocorneal adhesions and goniosynechiae. Congenital cataract was always present in eyes with multiple abnormalities. Intraocular pressures did not differ among horses with normal eyes and horses with multiple ocular abnormalities. Histologic examination of eyes corroborated the clinical appearance.

Complex limbal choristomas in linear nevus sebaceous syndrome

Objective This study aimed to describe the clinical and histopathologic findings in four patients with complex limbal choristomas associated with linear nevus sebaceous syndrome (LNSS), a rare disorder including nevus sebaceous, seizures, and mental retardation, and often accompanied by ocular anomalies. Design Small observational case series. Methods A retrospective review of the clinical and histopathologic records of four patients. Results Each of four patients had complex limbal choristomas in the setting of clinical and histopathologic LNSS. The limbal choristomas were multiple in three patients and bilateral in two patients. Most choristomas involved the superotemporal limbus (6 of 10), although nasal (3 of 10) and inferior (1 of 10) limbal tumors also were present. Three patients had significant corneal astigmatism or involvement of the central cornea requiring surgical removal of their choristomas, one accompanied by a lamellar keratoplasty and another accompanied by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient’s vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Histopathologic examination of the excised choristomas showed foci of lacrimal gland (3 of 4 patients), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Other associated ocular findings included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), scleral ectasia (1 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), and cortical visual impairment (1 of 4). Conclusions Complex limbal choristomas, although rare, can occur in the setting of LNSS and can be associated with multiple ocular and systemic abnormalities. Visual prognosis appears poor in most cases despite aggressive management.

Transgenic expression of IFN-gamma in the murine lens results in multiple ocular abnormalities and an early but self-limited inflammatory response.

The anterior chamber of the eye is known to be an immune privileged site, due to both local and systemic effects on the immune response. Injection of IFN-gamma into the anterior chamber (AC) overcomes the suppression of antigen-specific delayed hypersensitivity responses normally seen in the eye. Transgenic mice expressing increased IFN-gamma in the lens under the alpha A-crystallin promoter were produced to determine whether the proinflammatory effects of IFN-gamma would abolish immune privilege and promote loss of tolerance as has been seen in non-immune privileged tissues. Two alpha C/IFN-gamma transgenic lines are described which demonstrate multiple ocular and lenticular abnormalities some of which are developmental in origin and others that may be secondary to the inflammatory effects of IFN-gamma. A significant inflammatory cell infiltrate which is observed in the AC and vitreous from birth to 4 weeks of age, consists initially of macrophage and polymorphonuclear leukocytes and then CD4+ T lymphocytes. However, the infiltrate is essentially resolved by 6 weeks of age. Therefore, although lens-specific expression of IFN-gamma results in early loss of immune privilege, chronic uveitis does not occur probably due to the lack of continued IFN-gamma expression.

Morphologic changes in extraocular muscles of the dystrophic hamster.

Cardiomyopathic hamsters (UM-X7.1 strain) have demonstrable myopathy involving both skeletal and cardiac muscle. In addition, they have multiple ocular abnormalities. In this study, extraocular muscles were examined by light and electron microscopy. Changes observed within affected muscle fibers were variable and included coagulation necrosis, lysis of myofibrils, mitochondrial changes, and infiltration by phagocytic cells. Regenerative changes included duplication of myoblast nuclei, proliferation of sarcoplasmic reticulum, and myofibrillogenesis. The lesions are presumably myogenic in origin. The cardiomyopathic hamster may be useful as an animal model for certain types of ocular myopathy in man.