Alina A. Zubcov

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.

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Improvement of Visual Acuity after Surgery for Nystagmus

PURPOSE The authors compared the preoperative and postoperative binocular visual acuities and eye movement recordings of patients who underwent eye muscle surgery consisting of the Anderson-Kestenbaum procedure or the artificial divergence procedure modeled after Cüppers, or a combination of both procedures, for the treatment of infantile nystagmus with head turn. METHODS Binocular visual acuities and eye movement recordings by electro-oculography (EOG) were compared preoperatively with those done within 3 weeks postoperatively. Shifting and broadening of the minimal intensity zone and foveation time and changing of the waveform were measured. The treatment of 6 of 18 patients was based on the artificial divergence principle; for 7 patients, treatment was in accordance with the Anderson-Kestenbaum principle; and 5 patients had combined procedures. RESULTS The improvement in binocular visual acuities was two Snellen lines or more in one of six patients in the artificial divergence group and four of five patients in the combined treatment group. The EOG recordings showed shifting of the minimal intensity zone toward the primary position in all three groups. A broadening of the minimal intensity zone occurred mostly in the artificial divergence and combined groups. Increases in foveation time and changes in waveforms from jerk to jerk with foveation were found in three of six patients in the artificial divergence group and in two of five patients in the combined group. CONCLUSION With less muscle surgery, the artificial divergence and combined operations gave better vision improvement than the Anderson-Kestenbaum operation.

Intraocular recombinant tissue- plasminogen activator fibrinolysis of fibrin formation after cataract surgery in children

PURPOSE To evaluate the efficacy and safety of intracameral recombinant tissue plasminogen activator (rt-PA) application for fibrinolysis of fibrin formation after cataract surgery in children. SETTING Johann Wolfgang Goethe-University, Department of Ophthalmology, Frankfurt am Main, Germany. METHODS This study comprised 11 eyes of 10 patients aged 3 to 13 years (mean 7.2 +/- 3.68 [SD]) who developed severe fibrin formation after cataract surgery and IOL implantation despite intensive topical steroid therapy. Under general anesthesia, fibrinolysis was performed with 10 micrograms of rt-PA 7.18 +/- 2.04 days after intraocular surgery. Follow-up included slitlamp examination, tonometry, visual acuity testing, and-ophthalmoscopy. Anterior chamber flare measurements could be performed in 6 eyes. RESULTS Complete resolution of fibrin formations occurred in 90% of the patients in these cases, no recurrent fibrinous reaction or adverse effects were noted. In 2 eyes of the same patient with a history of juvenile rheumatoid arthritis and chronic uveitis, fibrin clot dissolution was incomplete. A recurrent fibrinous formation could be observed after 2 and 4 weeks, respectively. A beginning band keratopathy excluding the central and limbal cornea was noted after 6 and 8 weeks, respectively. CONCLUSION Intraocular application of rt-PA appears to be a safe and efficacious therapeutic approach in the management of severe fibrinous reactions after pediatric cataract surgery.

Ophthalmic manifestation of congenital protein C deficiency.

Under normal conditions activated protein C is a natural anticoagulant that cleaves 2 activated coagulation factors, factor Va and factor VIIIa, thereby inhibiting the conversion of factor X to factor Xa and of prothrombin to thrombin. Additionally, activated protein C enhances tissue-plasminogen activator-mediated fibrinolysis by inhibition of plasminogen activator inhibitor-1. This results in an increase in circulatory plasminogen activator levels. Protein C deficiency, a genetic or acquired thrombophilic abnormality, has been demonstrated to predispose to episodes of potentially blinding and lethal thromboembolic events. Heterozygous-deficient subjects usually remain asymptomatic until adolescence or adulthood. In homozygous-deficient patients, protein C activity is usually less than 1% (reference range, 70%-140%), resulting in thromboembolism as early as in the neonatal period. The major clinical symptoms in affected newborn infants have been purpura fulminans, vitreous hemorrhage, and central nervous system thrombosis. The age of onset of the first symptoms has ranged from a few hours to 2 weeks after birth, usually after an uncomplicated full-term pregnancy and delivery. In contrast to the genetic form, acquired neonatal protein C deficiency occurs particularly in ill preterm babies. Typical complications of prematurity such as respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis may also be present. In the medical literature, there are only a few reports of homozygous protein C deficiency in neonates. We present 2 cases of homozygous protein C deficiency with ocular and extraocular manifestation.

Electronic recording of occlusion treatment for amblyopia: potential of the new technology

BackgroundApproximately one third of all amblyopic eyes do not reach visual acuity of 20/40 in spite of occlusion therapy. One of the reasons is a lack of adherence to therapy, which, however, could not be quantified in the past. Experience with new devices (occlusion dose monitors, ODMs) for electronic recording of occlusion has recently been reported. The aim of the present study was to evaluate the potential of the ODMs developed in the Netherlands. Various features were tested, including the reliability of the ODM recordings compared to diaries, two ODMs used simultaneously on one patch, the influence of the ambient temperature, and the specificity of the recording pattern for measurements on the eye.MethodsThe ODMs were taped to the outside of the standard occlusion patch and measured the temperature difference between their front and back surfaces. Members of the research group and the families of two patients kept occlusion diaries while using the ODMs. Recorded and written occlusion periods were compared. Measurements were carried out under various conditions: patch with one ODM tightly on the eye or detached (allowing peeping); ODMs taped to various parts of the body; two ODMs simultaneously on one patch; variation of room temperature.ResultsThere was good correspondence between the occlusion times recorded by the ODMs and those from the diaries, as well as between the recordings of two ODMs used simultaneously on one patch. High ambient temperatures (33°C to 37°C) prevented reliable ODM measurements. Measurements on other parts of the body were misclassified with probabilities between P=0.099 and P=0.325 as measurements with the patch tightly on the eye.ConclusionsIn spite of some technical limitations, the ODMs provide a chance for reliable assessment of compliance and therefore objective information on dose–response function for occlusion therapy. This will lead to a more evidence-based treatment for amblyopia.

Treatment of Manifest Latent Nystagmus

Eight patients with manifest latent nystagmus, as noted by ocular movement recordings, were examined for nystagmus reduction after surgical or optical treatment. Seven of the patients had strabismus. Five patients underwent strabismus surgery, had no tropia postoperatively, and the manifest latent nystagmus converted to latent nystagmus. Four of these five patients subsequently showed improvement in binocular visual acuity. Three patients received optical treatment; one had accommodative esotropia and, with appropriate spectacle correction, the manifest latent nystagmus was converted to latent nystagmus with improved vision. In the other two patients the manifest latent nystagmus lessened after correction with appropriate spectacles; binocular visual acuity of one of these patients improved. The possibility of converting manifest latent nystagmus to latent nystagmus by strabismus surgery is a reasonable surgical goal. In patients with manifest latent nystagmus and strabismus, surgical or optical alignment of the eyes decreases the nystagmus intensity and may also improve binocular visual acuity.

Asymmetric Horizontal Tropias, DVD, and Manifest Latent Nystagmus: An Explanation of Dissociated Horizontal Deviation/Discussion: Asymmetric Horizontal Tropias, DVD, and Manifest Latent Nystagmus

Four patients with dissociated horizontal deviation (DHD) are described and an explanation of their horizontal comitant deviations is offered. The patients had asymmetric comitant horizontal deviations dependent on the fixing eye. All of them had unequal visual acuity (VA) and asymmetric manifest latent nystagmus (MLN) documented with eye movement recordings. The subjects appear to use convergence to reduce their nystagmus when viewing with the eye having more severe nystagmus and hence poorer vision. When patients viewed with the eye having less nystagmus, little or no convergence was exhibited. We suggest that DHD may be the manifestation of an asymmetric nystagmus blockage syndrome (NBS). The dampening effect of convergence on nystagmus has been well documented in the past and seems to apply here. The patients demonstrate that a true, but asymmetric NBS, can be found with MLN.

Stereopsis after primary in-the-bag posterior chamber implantation in children

Abstract Purpose: The purpose of this study was to evaluate visual acuity and binocular function after primary posterior chamber intraocular lens (IOL) implantation in children. Patients and Methods: A retrospective chart review of 39 eyes of 31 children was performed. Fifteen eyes with traumatic, 17 with developmental, and 7 with congenital cataracts without any other ophthalmologic problems were examined before and after cataract surgery (irrigation/aspiration procedure with implantation of a posterior chamber IOL). Twelve eyes also received a posterior capsulorrhexis and anterior vitrectomy. The mean age at surgery was 6.9 ± 3 years (range, 3-12 years). Results: Twenty (51%) of 39 eyes achieved a best-corrected postoperative visual acuity of 20/40 or better (range, 20/200-20/20). The mean postoperative visual acuity was 20/40 in the traumatic and developmental cataract groups and 20/100 in the congenital cataract group. There was a positive correlation between cataract morphology and visual acuity ( P P Conclusions: After capsular bag-fixated IOL, visual acuity and binocular function in children older than 3 years were favorable and the complication rate, excluding posterior capsule opacification, was low. (J AAPOS 1999;3:227-33)