Optic nerve hypoplasia and bilateral persistent fetal vasculature due to TUBA1A tubulinopathy.

PURPOSE: To describe a case of TUBA1A-associated optic nerve hypoplasia and persistent fetal vasculature. METHODS: Observational case report. RESULTS: A female, full term infant was found to have a Dandy-Walker malformation with cerebellar and brainstem hypoplasia, ventriculomegaly, and lissencephaly. Her ophthalmic exam was notable for persistent fetal vasculature, optic nerve hypoplasia, vitreous hemorrhage, and peripheral retinal non-perfusion. Subsequent genetic testing revealed a TUBA1A genetic variant. CONCLUSION: Persistent fetal vasculature, peripheral retinal vascular abnormalities, and optic nerve hypoplasia may be associated with TUBA1A variants. These patients should be carefully evaluated with dilated retinal exam and fluorescein angiography to detect retinal perfusion abnormalities requiring treatment.

Expanding the phenotype of a neurofibromatosis type 1-like syndrome: a patient with a SPRED1 mutation and orbital manifestations.

A 4-year-old child with no medical history presented for evaluation of a small, palpable nodule near the left inferolateral rim. The lesion had a bluish hue and had been slowly enlarging over the course of several months. MRI of the orbits revealed a heterogenous and infiltrative preseptal and extraconal mass which enhanced with gadolinium, and sphenoid wing dysplasia on the left. A complete ophthalmic and physical examination failed to reveal any other stigmata of neurofibromatosis type 1 (NF1) or neurofibromatosis type 2 (NF2). An incisional biopsy of the palpable mass revealed a plexiform neurofibroma. Molecular sequencing of the NF1 and NF2 genes did not reveal causative mutations. Further investigation revealed a loss of function mutation in SPRED1 on chromosome 15. Although loss of function mutations in the SPRED1 gene are known to cause several dermatologic changes associated with the NF1-like phenotype, to our knowledge, this is the first description of a SPRED1 gene mutation resulting in ophthalmic abnormalities.

The effect of topical tetracaine eye drops on emergence behavior and pain relief after strabismus surgery.

INTRODUCTION: Pediatric strabismus surgery may be associated with postoperative nausea, vomiting, and emergence agitation (restlessness, thrashing, crying, moaning, disorientation). We hypothesize that emergence agitation after strabismus surgery is in part related to pain and that topical tetracaine ophthalmic drops can decrease the intensity and incidence of postoperative pain and emergence agitation. METHODS: Eighty-eight subjects aged 1 to 12 years scheduled for strabismus surgery were enrolled in a double-masked randomized control trial. The patients were randomized to one of three groups: Group A received normal saline drops before and after surgery; Group B received normal saline drops before and tetracaine 1% drops after surgery; Group C received tetracaine 1% drops before and after surgery. An observer masked to group assignment assessed each patient in the postanesthesia care unit (PACU) using both a behavior scale and a modified behavioral pain scale. RESULTS: Patients in Group A were found to be in significantly more pain than Groups B or C at 5 minutes after arrival to the PACU (p < 0.013). Using the behavior scale, a significantly greater proportion of patients in Group A were crying or crying and thrashing at 5, 15, and 30 minutes after arrival to the PACU (5 minutes, p < 0.019; 15 minutes, p < 0.041; 30 minutes, p < 0.021). There was no significant difference between groups in total PACU time, PACU vomiting, PACU morphine use, or pain at home. CONCLUSIONS: Postoperative strabismus surgery pain was improved by the use of preoperative, and pre- and postoperative, tetracaine drops. Emergence agitation was not fully evaluated by the behavioral scale, and therefore, the effect of tetracaine drops on emergence agitation was not clarified. This study suggests that tetracaine drops can lead to a less stressful early postoperative experience for the patient.

Anterior Chamber Pathology in Alagille Syndrome.

BACKGROUND: Alagille syndrome is an autosomal dominant disorder characterized by neonatal cholestasis, characteristic facies, and cardiac abnormalities. Ocular abnormalities include posterior embryotoxon, mosaic pattern of iris stromal hypoplasia, microcornea, optic disc drusen, and pigmentary retinopathy. We present the second report of ocular pathology in two cases of Alagille syndrome. METHODS: Gross and histologic preparations of four eyes of two patients. RESULTS: Posterior embryotoxon is seen in both cases, with iris processes extending to the embryotoxon in case 1. Case 1 exhibited distinctly abnormal iris stroma with a prominent cleft separating the anterior and posterior stroma. Lacy vacuolization of the iris pigment epithelium was seen in case 2. CONCLUSIONS: Alagille syndrome is primarily a hepatic disorder but presents with several distinct ocular pathologic features, most specifically posterior embryotoxon. This and the unusual iris stroma may be caused by improper migration of neural crest cells due to mutation in the Jagged 1 gene that causes Alagille syndrome. Patients with Alagille syndrome rarely present to ocular autopsy. Pathology findings may help us better understand the pathophysiology of the ocular abnormalities in this disorder.

Visual loss with West Nile virus infection: a wider spectrum of a "new" disease.

We describe a case of severe visual loss as a result of West Nile virus (WNV) infection. Associated headache and fever led to the proper diagnosis and management, but the findings of optic neuritis, retinitis, and uveitis were a surprising and prominent component of the patient's meningitis syndrome. Physicians diagnosing and treating patients with WNV infection should be alerted to the possibility of ocular and optic nerve involvement, which may leave permanent neuropathic residua.

Effects of extraocular muscle surgery on 15 patients with oculo-cutaneous albinism (OCA) and infantile nystagmus syndrome (INS).

PURPOSE: The purpose of this report is to characterize the clinical and electrophysiological effects of extraocular muscle surgery in 15 patients with oculo-cutaneous albinism (OCA) and infantile nystagmus syndrome (INS). Our hypothesis is that surgery on the extraocular muscles of patients with OCA and INS changes their nystagmus and their visual function. DESIGN: Interventional, prospective, cohort, noncomparative case series. METHODS: All 15 patients had surgery on all four virgin horizontal recti; three for strabismus alone, three for nystagmus alone, five for an eccentric gaze null zone alone, and four for an eccentric gaze null zone plus strabismus. All patients have been followed for at least six months. All 15 patients had the subjective outcome measure of pre- and postoperative binocular best optically corrected acuity (BBOCA). Objective outcome measures included anomalous head posture (AHP) in nine patients, eye movement recording measures of expanded nystagmus acuity function (NAFX) in 10 patients, null zone position (NUZP) and null zone width (NUZW) in 10 patients, and foveation time (FOV) in nine patients. RESULTS: The results are summarized as follows; BBOCA increased 0.1 LogMar or greater in 14 of 15 patients. In those operated on for an AHP with or without associated strabismus the AHP improved significantly (P < .01 for all). The NAFX, NUZP, NUZW, and FOV measured from eye movement recordings showed persistent, significant increases in all patients (P < .01 for all). CONCLUSIONS: This report adds to the evidence that surgery on the extraocular muscles in patients with INS has independent neurologic and visual results.

West Nile virus-associated optic neuritis and chorioretinitis.

PURPOSE: To report the new ocular and neurologic features of West Nile virus (WNV) meningoencephalitis. DESIGN: Observational case report. METHODS: A 55-year-old woman presented with headache, stiff neck, visual loss, and fever 10 days after a weekend camping trip. Examination revealed vitritis, creamy yellow circular chorioretinal lesions, and peripheral visual field loss. RESULTS: Laboratory investigation indicated the patient was suffering from WNV meningoencephalitis with neuro-ocular involvement. CONCLUSION: Ophthalmologists and infectious disease specialists should recognize that the WNV infection spectrum may include ophthalmic findings, specifically optic neuritis and multifocal chorioretinitis.

The pediatric red eye.

There is a broad differential for the pediatric red eye, which may range from benign conditions to vision- and/or life-threatening conditions. This article presents a systematic differential, red flags for referral, and treatment options.

Mitochondrial tRNA-serine (AGY) m.C12264T mutation causes severe multisystem disease with cataracts.

Progressive multisystem disease should invoke consideration of potential mitochondrial etiologies. Mitochondrial disease can affect any organ system at any time, particularly involving neurologic, cardiac, muscular, gastroenterologic, and/or ophthalmologic manifestations. We report here a 19-year-old Caucasian man who was followed since birth in multiple pediatric subspecialty clinics for myelomeningocele complications. However, he progressively developed a host of additional problems that were not readily attributable to his neural tube defect involving developmental, ophthalmologic, cardiac, muscular, endocrine, and intermediary metabolic manifestations. Clinical diagnostic testing limited to analysis for common point mutations and deletions in his blood mitochondrial DNA (mtDNA) was not revealing. Skeletal muscle biopsy revealed abnormal mitochondrial morphology and immunostaining, mitochondrial proliferation, and mildly reduced respiratory chain complex I-III activity. Whole mitochondrial genome sequencing analysis in muscle identified an apparently homoplasmic, novel, m.12264C>T transition in the tRNA serine (AGY) gene. The pathogenicity of this mutation was supported by identification of it being present at low heteroplasmy load in his blood (34%) as well as in blood from his maternal grandmother (1%). The proband developed severe nuclear cataracts that proved to be homoplasmic for the pathogenic mtDNA m.12264C>T mutation. This case highlights the value of pursuing whole mitochondrial genome sequencing in symptomatic tissues in the diagnostic evaluation of suspected mitochondrial disease. Furthermore, it is the first report to directly implicate a single mtDNA mutation in the pathogenesis of ocular cataracts and clearly illustrates the important contribution of normal metabolic activity to the function of the ocular lens.

Survey of childhood blindness and visual impairment in Botswana.

BACKGROUND/AIMS: In terms of blind-person years, the worldwide burden of childhood blindness is second only to cataracts. In many developing countries, 30-72% of childhood blindness is avoidable. The authors conducted this study to determine the causes of childhood blindness and visual impairment (VI) in Botswana, a middle-income country with limited access to ophthalmic care. METHODS: This study was conducted over 4 weeks in eight cities and villages in Botswana. Children were recruited through a radio advertisement and local outreach programmes. Those ≤ 15 years of age with visual acuity <6/18 in either eye were enrolled. The WHO/Prevention of Blindness Eye Examination Record for Children with Blindness and Low Vision was used to record data. RESULTS: The authors enrolled 241 children, 79 with unilateral and 162 with bilateral VI. Of unilateral cases, 89% were avoidable: 23% preventable (83% trauma-related) and 66% treatable (40% refractive error and 31% amblyopia). Of bilateral cases, 63% were avoidable: 5% preventable and 58% treatable (33% refractive error and 31% congenital cataracts). CONCLUSION: Refractive error, which is easily correctable with glasses, is the most common cause of bilateral VI, with cataracts a close second. A nationwide intervention is currently being planned to reduce the burden of avoidable childhood VI in Botswana.

Simultaneous bilateral intraocular surgery in children.

BACKGROUND: Simultaneous bilateral intraocular surgery (SBIS), defined as sequential bilateral intraocular surgery completed in one visit to the operating room, is a controversial topic. The reluctance of ophthalmologists to perform SBIS has been mainly attributable to concerns about bilateral catastrophic complications (endophthalmitis, expulsive hemorrhage, or retinal detachment). Herein we report our experience with SBIS in children and review the literature. METHODS: The medical records of 44 patients who underwent 48 cases of SBIS between 1994 and 2009 were reviewed. Of the 48 cases, 27 were bilateral cataract extractions, 1 including intraocular lens placement; 21 were cases of bilateral glaucoma surgeries, including goniotomy, trabeculotomy, and filtering tube placement. Bilateral surgeries were performed in one session under general anesthesia with strict aseptic separation of the 2 surgeries. RESULTS: All but one of the cataract cases were performed in patients <1 year of age, and the majority (15/27) were performed in patients < or =1 month of age. Postoperative complications included aphakic glaucoma (5 patients) and reproliferation of lens material (3 patients). The majority of patients who underwent glaucoma procedures were <1 year of age (19/21), with 4 of 21 <1 month of age. One eye developed hyphema that required anterior chamber wash out. There were no catastrophic complications from the surgery or anesthesia (death, asphyxia, cardiac or respiratory arrest, or seizures) in either group. CONCLUSIONS: Simultaneous bilateral intraocular surgery was performed safely in 48 cases during a 15-year period. In selected pediatric cases requiring bilateral intraocular surgery for glaucoma or cataract, SBIS may reduce risks related to anesthesia and delayed surgery.

Age, gender, biometry, refractive error, and the anterior chamber angle among Alaskan Eskimos.

BACKGROUND: The prevalence of angle-closure glaucoma (ACG) is greater for Eskimos/Inuit than it is for any other ethnic group in the world. Although it has been suggested that this prevalence may be due to a population tendency toward shallower anterior chamber angles, available evidence for other populations such as Chinese with high rates of ACG has not consistently demonstrated such a tendency. METHODS: A reticule, slit-lamp, and standard Goldmann one-mirror goniolens were used to make measurements in the anterior chamber (AC) angle according to a previously reported protocol for biometric gonioscopy (BG) (Ophthalmology 1999;106:2161-7). Measurements were made in all four quadrants of one eye among 133 phakic Alaskan Eskimos aged 40 years and older. Automatic refraction, dilated examination of the anterior segment and optic nerve, and A-scan measurements of AC depth, lens thickness, and axial length were also carried out for all subjects. RESULTS: Both central and peripheral AC measurements for the Eskimo subjects were significantly lower than those previously reported by us for Chinese, blacks, and whites under the identical protocol. Eskimos also seemed to have somewhat more hyperopia. There were no differences in biometric measurements between men and women in this Eskimo population. Angle measurements by BG seemed to decline more rapidly over life among Eskimos and Chinese than blacks or whites. Although there was a significant apparent decrease in AC depth, increase in lens thickness, and increase in hyperopia with age among Eskimos, all of these trends seemed to reverse in the seventh decade and beyond. CONCLUSIONS: Eskimos do seem to have shallower ACs than do other racial groups. Measurements of the AC angle seem to decline more rapidly over life among Eskimos than among blacks or whites, a phenomenon also observed by us among Chinese, another group with high ACG prevalence. This apparent more rapid decline may be due to a cohort effect with higher prevalence of myopia and resulting wider angles among younger Eskimos and Chinese.

Ocular manifestations of hepatitis C virus infection.

Approximately 3.6 million persons in the United States are infected with the hepatitis C virus (HCV), a condition with both hepatic and extrahepatic sequelae. Although no pathognomonic manifestation of HCV infection in the eye has been demonstrated, associations between HCV infection and various ocular syndromes have been reported in small case series and individual patients. At this time, the ocular manifestations of HCV infections best supported by the literature include a dry eye syndrome similar to Sjögren syndrome, and ischemic retinopathy caused by either an HCV-induced vasculitis or treatment with interferon. Patients with diabetes seem to be more susceptible to interferon retinopathy and to subsequent permanent visual loss. There have been no cases of HCV transmission via corneal transplantation, suggesting that current cadaveric screening protocols are effective in preventing this route of transmission. Screening for HCV should be considered in patients with risk factors for HCV infection who suffer from unexplained ischemic retinopathy or dry eyes.