Richard M. Robb

Refractive Errors Associated With Hemangiomas of the Eyelids and Orbit in Infancy

Asymmetrical refractive errors, both astigmatic and myopic, were associated with infantile hemangiomas of the eyelids and orbit in 46% of 37 patients who had large lesions and upper eyelid involvement predisposing to the ammetropia. The axis of the astigmatic error related to the location of the eyelid hemangioma and correlated closely with keratometric measurements of corneal astigmatism. The refractive errors tended to be stable despite eventual resolution of the hemangiomas. Efforts to combat strabismic and refractive amblyopia were rewarding in many patients. A history of complete eyelid occlusion during part of the first year of life was associated with dense amblyopia and eccentric fixation in some patients, but in other patients this history was compatible with the eventual development of useful vision. Absence of an asymmetrical refractive error in patients with eyelid and orbital hemangiomas rendered the prognosis for vision good in involved eyes.

Studies on the development of the eye cup and optic nerve in normal mice and in mutants with congenital optic nerve aplasia

Abstract With the use of quantitative histological techniques, we have described, in normal mice, the formation of a system of intercellular channels within the embryonic retina and continuing without interruption into the optic stalk. The channels develop in advance of the morphological differentiation of the retinal ganglion cells and their neurites. Moreover, they appear at predictable times during gestation and are localized along the potential route to be taken by the earliest developing fibers of the optic nerve. A functional relationship may exist between the development of the channels and the subsequent outgrowth of the optic nerve from the eye. We have also examined a series of mouse embryos homozygous for the mutant gene ocular retardation (or J ), which causes optic nerve aplasia. In the or J mutant, there is a reduction in area of these extracellular spaces and the optic nerve fails to exit from the eye. The lack of intercellular space within the mutant retina is associated with an increased number of cells which, in turn, may result from a continuing absence of normal cell death during earlier stages.

The natural course of congenital obstruction of the nasolacrimal duct.

In order to establish the rate of spontaneous resolution of congenital obstruction of the nasolacrimal duct, 50 infants, referred from a local pediatric group practice over a period of five years, were followed from the time of first symptoms until 8 to 13 months of age. Among the 50 infants, 65 nasolacrimal ducts were blocked and 58 ducts in 44 patients opened spontaneously. Only seven ducts in six patients required probing for relief of the obstruction. During the same period another seven patients from various referral sources were seen because of noninflammatory swelling of the lacrimal sac at birth. These patients were also found to have nasolacrimal duct obstruction, but early surgical intervention was required in six of the seven patients to relieve the distention of the sac.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

SUCCESS RATES OF NASOLACRIMAL DUCT PROBING AT TIME INTERVALS AFTER 1 YEAR OF AGE

OBJECTIVE The purpose of the study was to determine the success rate of probing for congenital nasolacrimal duct obstruction after 1 year of age. DESIGN A record review. PARTICIPANTS AND INTERVENTION Two hundred fifty-two patients with 303 obstructed nasolacrimal ducts underwent probing and irrigation by the author between 1971 and 1997 while under brief general anesthesia. MAIN OUTCOME MEASURES Successful outcome of probing was defined as absence of tearing and discharge in the affected eye. RESULTS The overall cure rate in all patients was 92%, varying from 88.9% to 96.8% at different age intervals up to and beyond 3 years of age. Chi-square analysis showed no significant change in cure rate with increasing age. CONCLUSION Probing for congenital nasolacrimal duct obstruction beyond 1 year of age is highly successful, and the cure rate does not vary significantly at intervals of increasing age.

Glaucoma following childhood cataract surgery.

Glaucoma has been recognized as an infrequent but serious complication following surgery for congenital and acquired cataracts in childhood. Little is known concerning the influence of factors on the risk of glaucoma such as age at surgery, type of cataract, associated ocular abnormalities, and type of surgery. We reviewed records of 240 eyes of 155 patients on whom cataract surgery had been performed between January 1965 and July 1990 at Childrens Hospital, Boston. After excluding those patients who had been followed up less than 5 years after surgery, and those who had had surgery after the age of 10 years, 125 eyes of 82 patients were included in the study group. We identified 14 eyes of 9 patients that had developed open-angle glaucoma 5.3 to 13.1 years following surgery (average 7.4 years). An additional 4 eyes of 3 patients developed angle closure glaucoma, which was diagnosed at 146, 177, 2911, and 2939 days following surgery. A fifth patient developed acute angle closure 1.7 years following primary cataract surgery and 53 days following secondary discission. All but one of the patients who developed glaucoma had cataract surgery at less than 1 year of age. Age at surgery for the entire study group averaged 1.9 years, and ranged from 25 days to 9.6 years. We conclude that patients having cataract surgery before 1 year of age are at the greatest risk of developing postoperative open-angle glaucoma. Additional increased relative risk was found in eyes with microcornea, congenital rubella syndrome, and poor pupillary dilation with 1% cyclopentolate (Cyclogyl). No significant difference was seen among the various surgical methods of cataract removal.

Alzheimer's Disease Amyloid-β Links Lens and Brain Pathology in Down Syndrome

Down syndrome (DS, trisomy 21) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21) encoding the Alzheimers disease (AD) amyloid precursor protein (APP). Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-β peptides (Aβ), early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Aβ accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Aβ pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Aβ accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Aβ aggregates (∼5 to 50 nm) identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Aβ in DS lenses. Incubation of synthetic Aβ with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Aβ accumulation as a key pathogenic determinant linking lens and brain pathology in both DS and AD.

Results of early treatment of unilateral congenital cataracts

Twelve infants with unilateral congenital cataracts treated at Boston Childrens Hospital between 1978 and 1986 have now reached the age of 3.5 years or older. All infants had cataract extractions, aphakic contact lens fitting, and occlusion of the unaffected eye by 6 months of age. Patients with posterior lenticonus or persistent hyperplastic primary vitreous were excluded from this review. Early improvement of visual acuity in the aphakic eye was monitored by preferential looking tests, and occlusion of the sound eye was adjusted accordingly. E card visual acuities are now available on all 12 children. Five patients have 20/70 or better visual acuity, three patients have between 20/100 and 20/400 vision, and four patients have less than 20/400 in the aphakic eye. Two patients whose cataract surgery was done after 4 months of age had the poorest visual results. Difficulty maintaining occlusion therapy and interruptions of contact lens wear limited the development of better vision in some patients. The visual results to date in these 12 patients suggest that early aggressive treatment of unilateral congenital cataracts is worthy of consideration in most instances.

Outcome of Treatment for Bilateral Congenital Cataracts

The outcome of treatment for bilateral congenital cataracts was studied retrospectively in a group of 51 patients. Two major categories of lens opacities were identified. In the first category, the opacities were extensive and visual impairment was evident early in the first year. These cataracts often occurred in eyes with small corneal diameters and poorly dilating pupils. Postoperative strabismus was nearly universal; nystagmus developed in over 50%; and late onset open-angle glaucoma developed in 8 of the 29 patients studied. Early surgery did not seem to abort the development of nystagmus in this group of patients. In the second category, the lens opacities were partial, often lamellar in configuration, and visual impairment was less severe. Surgery was usually performed after 3 years of age, with good visual results if the opacities were symmetrical and there was no nystagmus. No deprivation amblyopia developed in this group, even when surgery was delayed into the second decade. Strabismus developed postoperatively in about a third, but so far, no delayed open-angle glaucoma has been identified.

Optic Disc Drusen in Children

Forty children with pseudopapilledema due to optic disc drusen (31 bilateral, nine unilateral) were studied retrospectively to characterize the early natural history of this condition. The average age at the first examination was 10.2 years (range 3.6 to 19.5 years), and the mean follow-up period was 44 months. Discrete hyaline bodies or papillary calcifications were first noted in one or both eyes with pseudopapilledema at a mean age of 12.1 years in 38 of 40 cases. Decreased visual acuity due to drusen occurred in only one eye due to subretinal neovascularization. Visual fields obtained in 35 eyes (21 patients) with pseudopapilledema showed an enlarged blind spot (9), an inferior arcuate/sector/or altitudinal defect (6), or both (3) in 18 eyes. Our study suggests that discrete papillary calcifications or hyaline bodies frequently emerge and visual field deficits are commonly detectable in the second decade of life in patients with pseudopapilledema due to optic disc drusen.