Two Cases of Oculofaciocardiodental (OFCD) Syndrome due to X-Linked BCOR Mutations Presenting with Infantile Hemangiomas: Phenotypic Overlap with PHACE Syndrome.

BACKGROUND: Oculofaciocardiodental (OFCD) syndrome is due to mutations in BCOR (BCL-6 corepressor). OFCD has phenotypic overlaps with PHACE syndrome (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac defects, Eye anomalies). Infantile hemangiomas are a key diagnostic criterion for PHACE, but not for OFCD. A previous study reported two cases of infantile hemangiomas in OFCD, but the authors could not exclude chance association. CASE PRESENTATION: We describe two novel cases of female patients (one initially diagnosed with PHACE syndrome), both of whom had infantile hemangiomas. Ophthalmological findings were consistent with oculofaciocardiodental (OFCD) syndrome. Upon genetic testing, these two females were determined to have X-linked BCOR mutations confirming OFCD syndrome diagnoses. CONCLUSION: These case reports add support to the hypothesis that infantile hemangiomas may be a feature of OFCD. BCOR may potentially be within a pathway of genes involved in PHACE syndrome and/or in infantile hemangioma formation.

Bacteriorhodopsin crystal growth in reduced gravity--results under the conditions, given in CPCF on board of a Space Shuttle, versus the conditions, given in DCAM on board of the Space Station Mir.

For the purpose of bio-electronics, bacteriorhodopsin was crystallized into two habits through liquid-liquid-diffusion, namely individual needles of up to 1.9 mm in length and needle bunch-like clusters of up 4.9 mm in total length. In both the reduced gravity experiments performed, the morphology of the individual needles (crystal form A) had improved in terms of sharp needle edges and compact needle packing, compared to the parallel ground controls. For the long duration wide range low gravity condition in the "Diffusion-controlled Crystallization Apparatus for Microgravity (DCAM)" on Mir (STS-89 up), needle bunches on average were longer there than on the ground, while the compactness of the clusters, i.e. the average ratio of clustered length to clustered width was the reverse. Some exceptionally large individuals needles were grown in DCAM. For the "Commercial Protein Crystallization Facility (CPCF)" in short duration high definition microgravity conditions during a science mission of the Space Shuttle Discovery (STS-95), size and shape of the individual needles were homogeneous and superior to those of both the parallel ground controls and the results in DCAM. In CPCF, the average volume of the individual needles in suspension was increased by 50% in microgravity compared to those in the ground control.

Posterior repositioning of glaucoma implants for anterior segment complications.

OBJECTIVE: To assess the efficacy of repositioning Baerveldt aqueous implant tubes from the anterior chamber into the vitreous cavity in the management of anterior chamber tube-related complications. DESIGN: Noncomparative case series. PARTICIPANTS: Nine eyes of eight consecutive subjects with anterior segment problems (corneal decompensation with a shallow anterior chamber or recurrent tube erosion unresponsive to conventional revision). INTERVENTION: Baerveldt implant tubes were repositioned from the anterior chamber into the vitreous cavity after pars plana vitrectomy. MAIN OUTCOME MEASURES: Preservation of visual acuity, maintenance of intraocular pressure (IOP) control, and resolution of the anterior segment problem. RESULTS: Nine eyes of eight subjects were collaboratively managed by the operating glaucoma and vitreoretinal surgeons and followed postoperatively for an average time of 17 months (range, 2-42 months). Visual acuity remained stable or improved in seven of the nine eyes. IOP remained controlled in all eyes, with an average IOP of 14.3 +/- 3.0 standard deviation mmHg (range, 10-18 mmHg). Progression of the anterior segment problem, which dictated the revision, was halted in three of five eyes with corneal decompensation and shallow anterior chambers and in all eyes with recurrent tube erosion. Postoperative complications included one successfully repaired retinal detachment occurring 9 months postoperatively. CONCLUSIONS: Repositioning of an anterior chamber Baerveldt shunt tube into the vitreous cavity is a viable option for resolving recalcitrant tube-related anterior segment complications.

Hollow-glass waveguide delivery of an infrared free-electron laser for microsurgical applications.

The purpose of this research is to deliver free-electron-laser (FEL) pulses for intraocular microsurgery. The FEL at Vanderbilt University is tunable from 1.8 to 10.8 microm. To deliver the FEL beam we used a metallic-coated hollow-glass waveguide of 530-mum inner diameter. A 20-gauge cannula with a miniature CaF2 window shielded the waveguide from water. Open-sky retinotomy was performed on cadaver eyes. The system delivered as much as 6 x 10(5) W of FEL peak power to the intraocular tissues without damage to the waveguide or to the surgical probe.

Optic nerve sheath fenestration with a novel wavelength produced by the free electron laser (FEL).

BACKGROUND AND OBJECTIVE: To determine whether 6.45-microm free electron laser (FEL) energy can successfully perform optic nerve sheath fenestration and to compare the acute and chronic cellular responses with this surgery. STUDY DESIGN/MATERIALS AND METHODS: Optic nerve sheath fenestration was performed in rabbits by using either FEL energy (< 2.5 mJ, 10 Hz, 325-microm spot size) or a knife. The optic nerve integrity and glial response were evaluated histologically acutely or 1 month postoperatively. RESULTS: The FEL at low energy effectively cut the optic nerve sheaths with minimal reaction in the underlying nerve. With FEL or knife surgical techniques, a mild astrocytic hypertrophy only adjacent to the fenestration was observed acutely in the glial fibrillary acidic protein (GFAP) -immunoreacted sections. The chronic healing responses after either technique appeared similar with: (1) a thin fibrous scar at the fenestration site, (2) cells uniformly distributed (hematoxylin and eosin), and (3) up-regulation of GFAP and S100beta in astrocytes adjacent to the fenestration site. CONCLUSION: The FEL at low energy performs an optic nerve sheath fenestration in a small space with ease. Both FEL and knife incisions cause a similar rapid glial response near the fenestration site that remains 1 month later.

Endoscopic goniotomy with the free electron laser in congenital glaucoma rabbits.

PURPOSE: Goniotomy is a surgical treatment of choice to treat primary infantile glaucoma. Goniotomy has been studied in vitro in animal and human cadaver eyes with several lasers. The objective of this study was to investigate the functional and morphologic effectiveness of goniotomy with the free electron laser in comparison with conventional needle goniotomy in early congenital glaucoma rabbits. MATERIALS AND METHODS: Ten rabbits with early congenital glaucoma underwent goniotomy over 100 to 120 degrees with a needle or the free electron laser. The wavelength was 6.45 microm, and the energy level ranged from 2.2 to 3.5 mJ at 30 Hz. Because most corneas were edematous in these rabbits, an Olympus 0.8-mm diameter endoscope was coupled to the laser waveguide or the needle and inserted into the anterior chamber filled with a viscoelastic material to perform the goniotomy. Intraocular pressures were followed up to 3 weeks before an acute goniotomy was performed in the contralateral eye. All eye specimens were processed for light microscopic evaluation. RESULTS: Incision of the pectinate ligaments and underlying trabecular meshwork was visualized through the endoscope on a video monitor during the surgeries. The mean intraocular pressure decreased after free electron laser goniotomy and after needle goniotomy, and the edematous corneas became clear in some cases. Histologic study showed successful lysing of the pectinate ligaments by the free electron laser with no obvious collateral thermal damage. However, some areas of peripheral anterior synechiae occurred. Similar results were observed in needle goniotomy cases. CONCLUSIONS: The free electron laser is capable of performing goniotomy in rabbit eyes with lower intraocular pressures in treated eyes 3 weeks after surgery. The histologic results of free electron laser goniotomy are comparable to those of conventional goniotomy. The endoscope provides beneficial visualization to perform the goniotomy in eyes with edematous corneas. The rabbit with early congenital glaucoma is also a useful infantile glaucoma surgical model.

Effect of acute intraocular pressure changes on short posterior ciliary artery haemodynamics.

BACKGROUND/AIMS: Vascular insufficiency due to abnormal autoregulation has been proposed as a major factor in the development of glaucoma. The anterior optic nerve is primarily perfused by the short posterior ciliary arteries. The autoregulatory capacity of these vessels in response to acutely elevated intraocular pressure (IOP) was examined in normal human subjects. METHODS: Colour Doppler imaging was performed on the short posterior ciliary arteries of 10 normal subjects at baseline and during four incremental IOP elevations. Using a scleral suction cup placed temporally, IOP was elevated to approximately 25, 30, 40, and 50 mm Hg. Additional measurements were performed immediately after pressure release. Systolic and diastolic flow velocities were measured and Pourcelot's resistivity index was calculated. RESULTS: Systolic and diastolic flow velocities decreased linearly with each incremental increase in IOP (p < 0.001). Pourcelot's resistivity index increased linearly with each incremental increase in IOP (p < 0.001). Changes in end diastolic velocity, peak systolic velocity, and Pourcelot's resistivity index were linearly related to changes in IOP. CONCLUSION: The normal healthy eye is not able to autoregulate to maintain PCA blood flow velocities in response to acute large elevations in IOP.

Half corneal light shield as a delivery system for standardized application of mitomycin C.

PURPOSE: The authors develop a simple and economical method of applying reproducible intraoperative doses of mitomycin C for glaucoma filtering surgery. METHODS: A three-part protocol was developed to study several properties of half corneal light shields (HCLSs). Part A tested the amount of mitomycin C (0.4 mg/ml) absorbed, the expansion dimensions attained, and the amount released to filter paper. In part B, the in vitro release of mitomycin C to an enucleated pig eye was examined. In part C, the in vivo release during intraoperative filtering surgery was tested. RESULTS: The amount of mitomycin C solution absorbed by the HCLSs ranged from 1.07 x 10(-2) mg to 1.19 x 10(-2) mg; expansion width ranged from 6.8 mm to 7.0 mm; expansion height ranged from 3.6 mm to 3.8 mm; expansion thickness was constant at 0.6 mm. The amount of solution released to filter paper ranged from 6.8 x 10(-3) mg to 8.6 x 10(-3) mg. The amount of solution transferred to the pig eye ranged from 1.0 x 10(-3) mg to 2.7 x 10(-3) mg. The amount of solution released in filtering surgery ranged from 2.0 x 10(-3) mg to 4.8 x 10(-3) mg. CONCLUSIONS: The contact surface area, the amount absorbed, and the amount released by each HCLS was reproducible. The uniform thickness theoretically provides a uniform distribution of mitomycin C. This method may allow standardization of intraoperative mitomycin C application, and may reduce the incidence of complications.

Reproducibility of laser Doppler flowmetry in the human optic nerve head.

PURPOSE: We sought to demonstrate reproducibility of the noninvasive laser Doppler flowmetry technique for measuring microvascular hemodynamics of the optic nerve head in human subjects. METHODS: Laser Doppler flowmetry was performed by four examiners on four human optic nerve heads during multiple sessions. Intersubject, interexaminer, intersession, and intrasession variabilities were calculated for velocity, blood volume, and blood flow (flux). RESULTS: Initial variability of measurements improved after 3 months' experience. The standard deviation of the intrasession variation for single readings was 18% of the velocity mean value and 24% of the flow (flux) mean value. Based on this, a sample size of 17 (power beta = 0.8, alpha = 0.05, paired t test) will demonstrate a 10% physiologic change in flux within a session if the average of five readings is used before and after the experimental perturbation. The intersession variation was 12% and 32% for velocity and flux, respectively. Because of this, a larger sample size or additional measurement sessions are required for detection of an experimental influence between two sessions. The coefficient of variation among subjects for single readings was 7% and 10% for velocity and flux, respectively. CONCLUSIONS: Reproducibility of velocity measurements is better than reproducibility of flux measurements. After experience with the method, laser Doppler flowmetry is sufficiently precise to permit feasible studies of human optic nerve head microvascular hemodynamics when physiologic perturbations are applied.

Autoregulation of human optic nerve head circulation in response to increased intraocular pressure.

The following experiments were undertaken to determine if blood flow is maintained by autoregulation in the human optic nerve head when circulation is challenged by elevated intraocular pressure, and to determine if the presence or absence of autoregulation is universal. Laser Doppler flowmetry was used to determine the average velocity, the number of moving erythrocytes, and the volume of flow in the capillary bed of the optic disc. These parameters were measured in 10 subjects at spontaneous levels of intraocular pressure (IOP), and at pressures artificially elevated to 25, 35, 45 and 55 mm Hg with a scleral suction cup. Four subjects (two who showed autoregulation and two who did not) were studied on six additional occasions to determine consistency of the findings. In these same four subjects a second location on the disc was also measured on six occasions to determine if the IOP-effect on blood flow varied by location. Of the 10 subjects initially studied, seven maintained the baseline level of blood flow over the lower part of the range of elevated intraocular pressure (evidence of autoregulation), but showed a decline in flow by the time IOP reached 45 or 55 mm Hg. Two subjects showed a linear decline in blood flow beginning with the smallest increment of elevation of IOP (no autoregulation), and one showed an uninterpretable result. The two individuals who showed the linear decline and two of those who showed efficient autoregulation were remeasured, and each showed consistently the same pattern as before when restudied on six different occasions each. However, at a different location on their discs, autoregulation was manifest in all of these four individuals. When challenged by elevated IOP, the optic nerve head typically maintains a steady-blood flow over a range of IOP, but fails to maintain the same flow by the time IOP reaches 45 or 55 mm Hg. Some disc locations, at least in some individuals, do not show this autoregulation, but exhibit a decline in blood flow linearly related to IOP, even with the modest elevation of IOP.

Ablation rate of PMMA and human cornea with a frequency-quintupled Nd:YAG laser (213 nm).

BACKGROUND AND OBJECTIVE: As an alternative to the standard excimer laser used for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas under controlled hydration. STUDY DESIGN/MATERIALS AND METHODS: The output of a frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian beam. PMMA and corneal lenticules maintained under controlled hydration were ablated until perforation was detected. RESULTS: The ablation rate of PMMA and cornea at 213 nm were similar to that at 193 nm when radiant exposure was below 200 mJ/cm2 and increased gradually between one and two times faster than that at 193 nm when radiant exposure was > 200 mJ/ cm2. CONCLUSIONS: PMMA and cornea ablation at 213 nm are similar to that at 193 nm and are different from that at 248 nm. The difference between PMMA and cornea ablation rates should be considered when using PMMA to test ablated diopter and smoothness for photorefractive surgery.

Acute IOP elevation with scleral suction: effects on retrobulbar haemodynamics.

AIMS/BACKGROUND: Mechanical and vascular factors may both contribute to glaucoma. This study investigated the relation of mechanical to vascular factors by examining how acute IOP elevation altered flow velocities in the central retinal and ophthalmic arteries. METHODS: IOP was elevated from a baseline near 14 to approximately 45 mm Hg using suction ophthalmodynamometry. During recovery from scleral suction, IOP fell to near 8 mm Hg. At each IOP, peak systolic and end diastolic velocities (PSV and EDV) were measured in the central retinal and ophthalmic arteries using colour Doppler imaging (Siemens Quantum 2000). Eleven healthy people served as subjects. RESULTS: Acute elevation in IOP had no effect upon PSV, EDV, or the derived resistance index in the ophthalmic artery: flow velocities in this vessel were identical at IOP of 8 mm Hg or 45 mm Hg. In contrast, in the central retinal artery, PSV and EDV fell, and the resistance index rose, in steady progression as IOP was acutely elevated (each p < 0.01). At IOP of 45 mm Hg, EDV was virtually absent and the resistance index was very nearly 1.0. CONCLUSION: Ophthalmic arterial haemodynamics are unrelated to acute fluctuations of the IOP over a wide range, suggesting that ocular hypertension itself cannot induce vascular dysfunction in this artery. In contrast, flow velocities in the central retinal artery were highly IOP dependent, implying that haemodynamic and mechanical factors are closely linked in this vascular bed.

Laser Doppler flowmetry measurement of changes in human optic nerve head blood flow in response to blood gas perturbations.

PURPOSE: The objective of this study was to establish the ability of laser Doppler flowmetry to detect relative changes in human optic nerve head hemodynamics caused by physiologic blood gas perturbations. METHODS: Laser Doppler flowmetry permits the noninvasive assessment of relative blood velocity, volume, and flow (flux) in a sample volume of the nerve head. Such measurements were performed in two groups of healthy subjects. The first group (n = 11) was tested during normal room air breathing and then while breathing 100% oxygen (isocapnic hyperoxia). The second group (n = 10) was also tested under normal conditions as well as during isoxic hypercapnia (+ 15% end-tidal carbon dioxide). Results were analyzed by paired t tests. RESULTS: Hyperoxia created a significant 25% (p = 0.002) decrease in optic nerve head blood flow, with blood volume decreased by 9% (p = 0.095) and blood velocity reduced by 13% (p = 0.154) compared to the room air condition. During hypercapnia, optic nerve head blood flow was increased by 28% (p = 0.012), with blood volume increased by 22% (p = 0.017) and blood velocity increased by 9% (p = 0.218) as compared to the normal room air condition. CONCLUSION: Blood flow in the optic nerve head capillaries changes in response to hyperoxia and hypercapnia as demonstrated in the brain and retina. Laser Doppler flowmetry permits the noninvasive assessment of these responses in humans under conditions within the physiologic range.

One-year follow-up results of combined mitomycin C trabeculectomy and extracapsular cataract extraction.

PURPOSE: When patients with glaucoma require cataract surgery, combined procedures offer important advantages over cataract surgery alone. Because mitomycin C has improved the success rate of a trabeculectomy in patients at high risk for filtration failure, the authors investigated whether it also would increase the survival rate of functioning filters in combined procedures. METHODS: Patients with both cataract and glaucoma underwent combined mitomycin C trabeculectomy, extracapsular cataract extraction, and intraocular lens implantation. Mitomycin C (0.5 mg/ml) was applied topically to the trabeculectomy site for 5 minutes before the cataract extraction. Intraocular pressure (IOP), visual acuity, and astigmatism were measured preoperatively and postoperatively. One-year results are available for 74 patients. RESULTS: At 1 year, 54 (73%) of 74 patients had IOPs of 15 mmHg or less without glaucoma medications. Visual acuity was 20/40 or better in 44 (60%) of 74 patients. Ten (15%) patients had a shift of more than 2 diopters of astigmatism against the rule compared with preoperative values. No notable corneal epithelial toxicity was present. Postoperative symptomatic hypotony with the wound construction occurred in 3 (4%) of 74 patients, with 1 patient requiring surgical revision. Other potential complications of mitomycin C include endothelial toxicity (1 patient had decreased vision due to endothelial folds) and wound stability (1 patient had wound rupture after direct ocular trauma). CONCLUSION: The 1-year survival rate of a functioning trabeculectomy using mitomycin C in combined glaucoma and cataract surgery is encouraging. The longer-term benefits and possible adverse effects of mitomycin C in combined procedures are unknown and continue to be investigated.

Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene.

OBJECTIVE: To diagnose the carriers and noncarriers in a family affected with Norrie disease based on molecular analysis. DESIGN: Family members from three generations, including one affected patient, two obligate carriers, one carrier identified with linkage analysis, one noncarrier identified with linkage analysis, and one female family member with indeterminate carrier status, were examined clinically and electrophysiologically. Linkage analysis had previously failed to determine the carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene with single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing. RESULTS: Ophthalmoscopy and electroretinographic examination failed to detect the carrier state. The affected individuals and carriers in this family were found to have a transition from thymidine to cytosine in the first nucleotide of codon 39 of the Norrie disease gene, causing a cysteine-to-arginine mutation. Single-strand conformation polymorphism analysis identified a patient of indeterminate status (by linkage) to be a noncarrier of Norrie disease. CONCLUSION: Ophthalmoscopy and electroretinography could not identify carriers of this Norrie disease mutation. Single-strand conformation polymorphism analysis was more sensitive and specific than linkage analysis in identifying carriers in this family.

Systemic diseases associated with nonarteritic anterior ischemic optic neuropathy.

PURPOSE: We investigated, in nonarteritic anterior ischemic optic neuropathy, the prevalence of various systemic diseases before or at its onset and the incidence of subsequent morbidity and mortality. METHODS: We investigated prospectively the presence of systemic diseases before or at the onset of nonarteritic anterior ischemic optic neuropathy in 406 patients. The information was obtained by complete medical history and physical examination. The prevalence rates of systemic diseases in young, middle-aged, and elderly groups were compared with those in the general population. We also analyzed the influence of systemic diseases on subsequent morbidity and mortality. RESULTS: Compared with the prevalences reported in the general population, our patients in each of the three age groups showed a significantly higher prevalence of arterial hypertension (P < or = .02), diabetes mellitus (P < .01), and gastrointestinal ulcer (P < or = .02). Also, middle-aged and elderly patients showed a significantly higher prevalence of ischemic heart disease (P < .01) and thyroid disease (P < .01). Middle-aged patients had significantly higher rates of chronic obstructive pulmonary disease and cerebrovascular disease (P < or = .01). After onset of anterior ischemic optic neuropathy, patients with both arterial hypertension and diabetes mellitus had a significantly higher incidence of cerebrovascular disease (P < .01). CONCLUSIONS: Nonarteritic anterior ischemic optic neuropathy is a multifactorial disease in which some systemic diseases may act as predisposing factors and others as precipitating factors. Patients with anterior ischemic optic neuropathy show no significant increase in mortality, but those with both arterial hypertension and diabetes mellitus have significantly (P < .01) increased incidence of cerebrovascular disease.

Experimental endoscopic goniotomy. A potential treatment for primary infantile glaucoma.

PURPOSE: The purpose of this study is to determine if an endoscope would improve visualization of the anterior chamber angle and facilitate goniotomy in a surgical cloudy corneal model of primary infantile glaucoma. METHODS: A 23-gauge needle coupled to a 0.8-mm diameter flexible endoscope entered the anterior chamber of porcine cadaver eyes through a corneal incision near the limbus. Internal structures were observed on a videoscreen and recorded as the needle approached and incised pectinate ligaments near Schwalbe's line. The eyes were then prepared for light microscopy and scanning electron microscopy. RESULTS: Internal structures were clearly visualized on the videoscreen during the goniotomy. The incision of pectinate ligaments was accompanied by the iris falling back and opening of the trabecular meshwork compared with the untreated portion of the angle. This was confirmed histopathologically. CONCLUSIONS: An endoscope coaxially coupled to a goniotomy needle tip allows visualization of the anterior chamber angle during goniotomy in the pig despite the presence of a cloudy cornea. The porcine anterior chamber angle is a useful animal model for studying the surgical treatment of primary infantile glaucoma.