A novel mutation in intron 11 of the COL2A1 gene in a patient with type 1 Stickler syndrome.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M F Goldberg.
Explore the source record for details and available documents.
The retina serves as an excellent model in which to study vertebrate CNS development. We have discovered a spontaneous mutation in the Sprague-Dawley rat that results in a novel and unusual ocular phenotype, including retinal abnormalities, that we have named Nuc1. We have previously shown that the Nuc1 mutation appears to suppress programmed cell death in the developing retina. Here we report that maturation of both the retinal neurons and the retinal vessels is abnormal in Nuc1 homozygous rats. The developmental changes in the retinal neurons and vasculature are correlated with regard to degree of abnormality. As Nuc1 homozygotes mature, focal retinal detachment begins at approximately 3 months after birth, and near total traction retinal detachment, associated with pre-retinal fibrosis and neovascularization, is evident by 18 months. Electroretinographic studies at 2.5 months of age indicate that functional retinal degeneration precedes retinal detachment. The functional abnormality is most evident in rods and the inner retina, and is present in homozygous but not heterozygous mutants. Immunocytochemical studies of rod and cone photoreceptors indicate abnormalities in rod, but not cone, photoreceptors in Nuc1 homozygotes, consistent with the electroretinographic findings. In Nuc1 animals, the Muller cells are activated. Although such activation may result from inflammation, Muller cells in Nuc1 may be reacting to a neuronal influence. It appears that the Nuc1 mutation plays a regulatory role in both developing and maturing ocular tissues. The Nuc1 mutation may also serve as an important genetic tool to explore the relationships that may exist among gliosis, normal neuronal development, and normal vascular development and how abnormalities in these associations lead to common retinal diseases.
Explore the source record for details and available documents.
PURPOSE: To report a dramatic occlusive event of the macula surrounding the foveal avascular zone, causing severe and permanent loss of vision in a child with sickle cell disease. METHODS: Case report. A nine-year-old boy with SS hemoglobinopathy and oculocutaneous albinism developed acute unilateral loss of vision. RESULTS: Ophthalmoscopy revealed a pale, milky white, thickened retinal lesion centered on the fovea in the right eye as well as foveal hypoplasia in the left eye. The presence of macular malformation associated with oculocutaneous albinism precluded formation of a cherry-red spot. Fluorescein angiography of the right eye demonstrated extensive occlusions of the arterioles surrounding the foveal avascular zone. The presence of occlusions surrounding the fovea from multiple directions suggested the possibility of central retinal artery occlusion with migration of microemboli downstream. CONCLUSION: The patient, the youngest case reported, developed an irreversible macular infarction that was not improved by an exchange erythrocyte transfusion. He was placed on a long-term monthly transfusion protocol to protect his unaffected eye.
PURPOSE: To report ocular and renal findings specific to the inheritable entity called papillorenal (also known as renal-coloboma) syndrome and relate these to a common cause. DESIGN: Observational case series and genetic study. PARTICIPANTS: Two unrelated probands presenting with absent central retinal vessels and 11 available family members. TESTING: Doppler ultrasonographic imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations were performed. In selected cases, indocyanine green angiography, scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements, visual evoked potentials, and magnetic resonance imaging were also performed. MAIN OUTCOME MEASURES: Better defined characteristics of the papillorenal syndrome. RESULTS: Numerous cilioretinal vessels were present with rudimentary or absent central retinal vessels. Superonasal visual field defects, typical for papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in two affected members of one family (with previously unsuspected renal failure in one case), and recurrent pyelonephritis was discovered in four affected members of the other family. No PAX2 mutations were detected. CONCLUSIONS: In the papillorenal syndrome, the hereditary absence of central retinal vessels may be missed, leading to confusion with isolated coloboma, low-tension glaucoma, and morning glory anomaly. Greater awareness of this syndrome will avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic counseling. We propose that the papillorenal syndrome is a primary dysgenesis that causes vascular abnormalities predominantly affecting the eye, kidney, and urinary tract, leading to hypoplasia of these structures. The absence of defects in the PAX2 gene in these families suggests that mutations in other genes may also be responsible for this syndrome.
Explore the source record for details and available documents.
PURPOSE: Ocular ischemia from polyarteritis nodosa (PAN) is rare. The authors present a case of multifocal ocular infarction from PAN. METHODS AND RESULTS: A 70-year-old woman developed hand and foot numbness followed by intermittent blurred vision and binocular horizontal diplopia. Two weeks later, she suddenly lost vision in the right eye from a central retinal artery occlusion and then developed a left anterior ischemic optic neuropathy and bilateral triangular choroidal abnormalities consistent with infarction. Her erythrocyte sedimentation rate and C-reactive protein were elevated. Although giant cell arteritis was suspected, a multiple mononeuropathy was demonstrated by electromyogram and nerve conduction velocity studies. Biopsy specimens from her sural nerve and biceps muscle showed a necrotizing vasculitis with fibrinoid necrosis, consistent with PAN. CONCLUSIONS: Polyarteritis nodosa can produce ischemia of a variety of ocular structures, including the retina, choroid, and optic nerve. In our patient, all three structures were affected. To our knowledge, this is the first reported case of the triangular sign of Amalric in PAN.
OBJECTIVE: To identify risk factors associated with higher rates of ocular complications in children with traumatic hyphema. METHODS: Consecutive inpatient records from July 1990 through December 1997 were retrospectively reviewed for all children (aged < or = 18 years) who were admitted to the Wilmer Ophthalmological Institute, Baltimore, Md, within 48 hours of a closed-globe injury leading to hyphema. Data obtained included age, sex, race, sickle cell status, initial and final visual acuities, hyphema size and intraocular pressure at presentation, the occurrence of a secondary hemorrhage, subsequent intraocular pressure elevations, and therapeutic interventions. RESULTS: Forty children fulfilled the inclusion criteria: 20 African American, 1 Asian American, and 19 white. Five of the 20 African American children had sickle cell trait, and 1 had sickle cell anemia. The rate of secondary hemorrhage was statistically higher in the African American population (P =.05), but no statistical difference existed between the rate of secondary hemorrhage in patients with and without sickle cell hemoglobinopathy. Sickle cell hemoglobinopathy was associated with a higher intraocular pressure at presentation (P =.03) and during inpatient follow-up (P =.02). CONCLUSIONS: In the setting of traumatic hyphema, African American children appear to be at greater risk for developing a secondary hemorrhage. In our patients, sickle cell hemoglobinopathy increased the risk of intraocular pressure elevation, but did not seem to increase the risk of rebleeding beyond that associated with race. Larger studies are needed to validate these observations.
Explore the source record for details and available documents.
PURPOSE: To determine if an ongoing infection control program is associated with a reduction in rates of nosocomial outbreaks of epidemic keratoconjunctivitis (EKC) and outbreak morbidity from nosocomial EKC in a large teaching eye institute. METHODS: The number of nosocomial EKC outbreaks, the number of affected patients, and the total number of patient visits were collected for each year between 1984 and 1997. An infection control program was implemented in 1992. The program included specified methods of patient screening and isolation, handwashing, instrument disinfection, medication distribution, and furlough of infected employees. The program included two levels of intensity of infection control measures, for non-outbreak and outbreak conditions. We compared rates per 100,000 patient visits of nosocomial outbreaks of EKC and affected patients for the 6-year period after the program was implemented, 1992-1997, with corresponding rates for 1984-1991. RESULTS: One, to three nosocomial outbreaks of EKC occurred annually in the period 1984-1991. After the implementation of the infection control program, no nosocomial outbreaks occurred in three of six years studied. In the pre-infection control years 1984-1991, there were 3.89 outbreaks and 54.09 affected patients per 100,000 visits, respectively. For the post-infection control years 1992-1997, the corresponding rates were 0.54 outbreaks and 5.66 affected patients per 100,000 patient visits. Rates for both outbreaks and affected patients were significantly lower for the post-implementation period (p < 0.005 and p < 0.0005, respectively). CONCLUSIONS: An ongoing infection control program was associated with decreased rates of nosocomial EKC outbreaks and outbreak morbidity from nosocomial EKC in our institute. Although several reports have described infection control measures that terminated individual outbreaks of nosocomial EKC, this study demonstrates that an ongoing infection control program may preemptively reduce nosocomial EKC outbreaks.
OBJECTIVE: To establish a communication between an obstructed retinal vein and the choroid by means of laser in eyes with nonischemic central or branch vein occlusion. METHODS: Retrospective review identified eyes with nonischemic central or branch vein occlusion, and with decreasing or persistently decreased visual acuity of 20/100 or worse for 4 months or more before treatment, that received 1 or more sessions of laser photocoagulation to create a chorioretinal anastomosis. RESULTS: Of 24 eyes with central vein occlusion, an anastomosis formed in 9 (38%) within 2 months after treatment, with visual improvement of 6 or more lines in 2 (8%) of 24 eyes, 1 to 3 lines in 5 (21%), and no improvement in 2 (8%). Of 6 eyes with branch vein occlusion, an anastomosis formed in 3 (50%) within 2 months after treatment, with visual improvement of 1 to 3 lines in 2 (33%) of 6 and no improvement in 1 (16%). No permanent, vision-limiting complications occurred during a mean follow-up of 13 months after the first treatment session or 8 months after the last session. CONCLUSIONS: Laser photocoagulation of a retinal vein and Bruch's membrane may create a chorioretinal anastomosis in some eyes with a nonischemic vein occlusion. Progression to an ischemic status may possibly be prevented with successful anastomosis formation. Marked visual improvement may occur. Treatment techniques to create reliably an anastomosis with subsequent visual improvement, while minimizing potential complications, continue to evolve.
OBJECTIVE: To assess the morphologic characteristics of the foveal abnormality in juvenile X-linked retinoschisis using the scanning retinal thickness analyzer (RTA). This characteristic foveal abnormality is present in 83% to 100% of patients with X-linked retinoschisis and has not been demonstrated histopathologically. METHODS: The RTA is a noncontact imaging device. The RTA scans an obliquely oriented slit laser beam across the macula to obtain a series of optical cross sections, which are digitized. PARTICIPANTS: The RTA was used to examine 7 eyes of 5 patients with X-linked retinoschisis. RESULTS: The RTA demonstrated foveal schisis in all eyes examined. In 2 eyes of 2 patients, a single schisis cavity, with an inner leaf in a dome-shaped configuration, was present. In 4 eyes of 3 patients, a single schisis cavity containing fine strands was present. Some of these strands partially, and others completely, bridged the cavity. In 1 eye of 1 patient, 2 separate schisis cavities with bridging strands were present in the fovea. CONCLUSIONS: Scanning RTA is a noninvasive imaging modality capable of producing optical cross sections that demonstrate the extent and structural details of the foveal schisis in X-linked retinoschisis. Scanning RTA seems to be effective in the detection, characterization, and quantification of foveal schisis.
OBJECTIVE: This study aimed to examine the characteristics of intraretinal changes associated with macular holes and epiretinal membranes by scanning retinal thickness analysis. STUDY DESIGN: The study design was a nonconsecutive case series. PATIENTS: Fifty-six eyes of patients who had either a suspected or clinically diagnosed macular hole or epiretinal membrane were recruited. INTERVENTIONS: A commercial prototype of the scanning retinal thickness analyzer (RTA) was used. It projected a laser slit beam onto the retina and scanned it, in 200 or 400 msec, across a 2- x 2-mm area, yielding multiple optical cross sections that were recorded digitally. RESULTS: Epiretinal membranes were detected, and sites of attachment could be identified. Full-thickness holes corresponded to intraretinal cavities in which the inner retinal surface was broken, usually at the center. The majority of eyes with full-thickness macular holes showed increased retinal thickness surrounding the hole. The so-called "cuff of subretinal fluid," however, often was not present by retinal thickness analysis, despite clinical diagnosis to the contrary, even though retinal thickness analysis is capable of detecting such fluid. In 20 (42%) of 47 eyes diagnosed or suspected of having macular holes, scanning retinal thickness analysis showed findings different from those reported by retinal specialists. CONCLUSIONS: Examination of macular holes with the scanning RTA provides useful information in the diagnosis of macular holes in addition to that obtained through conventional techniques. The findings support the idea that many macular holes develop in association with intraretinal cystic changes. The precise chronology of the events remains to be determined.
Explore the source record for details and available documents.
PURPOSE: To describe macular vasculopathy in incontinentia pigmenti. METHODS: Twelve baby girls with incontinentia pigmenti were examined under general anesthesia by fluorescein angiography of the macula. Nine eyes of 9 patients had sufficient detail to allow evaluation of capillary changes. Angiography was initiated as early as 3 months of age and was repeated in 7 eyes at 3- to 12-month intervals. Changes in capillary patterns were identified. RESULTS: Irregularly enlarged or distorted foveal avascular zones were noted in all 9 maculas. Sparseness of the perifoveolar capillary bed was a characteristic finding. Sequential macular angiography demonstrated non-progressive (stable) capillary closure in 2 eyes; progressive closure in another macula; progressive closure plus addition or reopening of macular capillaries in 3 eyes; and central retinal artery occlusion, with cherry-red spot formation, in 1 eye at 12 days of age. In addition, progressive tractional detachment of the macula occurred in 2 of these eyes, and progressive macular neovascularization occurred in 1 eye. CONCLUSIONS: Macular ischemia is characteristic of incontinentia pigmenti and is often progressive. It is the initiating event of a typical vasculopathy, characterized by capillary remodelling and, occasionally, by neovascularization and tractional detachment of the retina.
Explore the source record for details and available documents.
BACKGROUND AND OBJECTIVE: To investigate the incidence and patterns of posterior zones of relative decreased choroidal blood flow in patients with exudative age-related macular degeneration. PATIENTS AND METHODS: Digital indocyanine green (ICG) angiograms from 100 patients with exudative age-related macular degeneration were reviewed for the presence of posterior zones of relative decreased choroidal blood flow. The patterns of these zones and their location relative to the choroidal neovascular process were noted. RESULTS: Ninety-five percent of the angiograms displayed the presence of either a complete or an incomplete zone of relative choroidal hypoperfusion. The zone was most apparent in the early frames of the angiogram. Five different patterns of relative decreased choroidal blood flow were identified: horizontal (32%), vertical (14%), bipartite (9%), tripartite (31%), and quadripartite (9%). The choroidal neovascular process was located within or at the edge of the zone of relative choroidal hypoperfusion in all cases. CONCLUSION: Most cases of choroidal neovascularization localize to areas of relative choroidal dye nonfilling on ICG angiography. These patterns of choroidal nonfilling may have implications in the pathogenesis and management of choroidal neovascular membranes in age-related macular degeneration.
PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. METHODS: Seventy-two patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. RESULTS: Information from follow-up of 6 months or longer was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch's membrane in 15 eyes, scleral-thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged perhaps to have contributed to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physician's experience in using transscleral laser retinopexy. CONCLUSIONS: In this multicenter study, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.