Dynamic In Vivo Chest X-ray Dark-Field Imaging in Mice.

X-ray grating interferometry is a powerful emerging tool in biomedical imaging, providing access to three complementary image modalities. In addition to the conventional attenuation modality, interferometry provides a phase modality, which visualizes soft tissue structures, and a dark-field modality, which relates to the number and size of sub-resolution scattering objects. A particularly strong dark-field signal originates from the alveoli or air sacs in the lung. Dark-field lung radiographs in animal models have already shown increased sensitivity in diagnosing lung diseases, such as lung cancer or emphysema, compared to conventional X-ray chest radiography. However, to date, X-ray dark-field lung imaging has either averaged information over several breaths or has been captured during a breath hold. In this paper, we demonstrate the first time-resolved dark-field imaging of a breath cycle in a mechanically ventilated mouse, in vivo, which was obtained using a grating interferometer. We achieved a time resolution of 0.1 s, visualizing the changes in the dark-field, phase, and attenuation images during inhalation and exhalation. These measurements show that the dark-field signal depends on the air volume and, hence, the alveolar dimensions of the lung. Conducting this type of scan with animal disease models would help to locate the optimum breath point for single-image diagnostic dark-field imaging and could indicate if the changes in the dark-field signal during breath provide a diagnostically useful complementary measure.

Phase contrast X-ray imaging for the non-invasive detection of airway surfaces and lumen characteristics in mouse models of airway disease.

We seek to establish non-invasive imaging able to detect and measure aspects of the biology and physiology of surface fluids present on airways, in order to develop novel outcome measures able to validate the success of proposed genetic or pharmaceutical therapies for cystic fibrosis (CF) airway disease. Reduction of the thin airway surface liquid (ASL) is thought to be a central pathophysiological process in CF, causing reduced mucociliary clearance that supports ongoing infection and destruction of lung and airways. Current outcome measures in animal models, or humans, are insensitive to the small changes in ASL depth that ought to accompany successful airway therapies. Using phase contrast X-ray imaging (PCXI), we have directly examined the airway surfaces in the nasal airways and tracheas of anaesthetised mice, currently to a resolution of approximately 2 microm. We have also achieved high resolution three-dimensional (3D) imaging of the small airways in mice using phase-contrast enhanced computed tomography (PC-CT) to elucidate the structure-function relationships produced by airway disease. As the resolution of these techniques improves they may permit non-invasive monitoring of changes in ASL depth with therapeutic intervention, and the use of 3D airway and imaging in monitoring of lung health and disease. Phase contrast imaging of airway surfaces has promise for diagnostic and monitoring options in animal models of CF, and the potential for future human airway imaging methodologies is also apparent.

Off-axis photorefractive eye screening in children.

PURPOSE: To determine the utility of mass photoscreening for detecting visual anomalies in young, school-age children. SETTING: Seventy elementary schools in Alabama, Florida, Georgia, North Carolina, and Virginia, USA. METHODS: An off-axis photorefractive technique was used to screen 14,591 children in kindergarten, first, and fourth grades in 70 schools in 5 southeastern states in the United States. RESULTS: A total of 14,075 (96.5%) of the screenings yielded analyzable photographs. Overall, 647 (4.6%) children had significant ocular findings; significant was defined as hyperopia 2.50 diopters (D) or more, myopia 1.00 D or more, anisometropia 1.00 D or more, astigmatism 2.00 D or more, media opacity 1.0 mm or more in diameter, or 5 degrees or more or 10.00 prism diopters or more of ocular misalignment. Another 950 (6.7%) had possibly significant findings, defined as the sign being present but in an amount less than that considered significant. The most common refractive error was myopia (4.5%), followed by anisometropia (3.1%), hyperopia (2.9%), and astigmatism (1.0%). Alignment problems were found in 1.7% and media opacities in 0.1%. Among the 1.0% with other ocular anomalies were cases of anisocoria greater than 2.0 mm or irregular pupils, ptosis greater than 2.0 mm, and subconjunctival hemorrhages. In all, 202 children had significant anomalies thought to predispose to amblyopia, including 196 with significant anisometropia and 6 with significant lens opacities. At a screening cost of $5 per child for the whole study, the cost of identifying these children with potentially blinding eye disease was $361 each. CONCLUSION: Mass photoscreening may be used to detect amblyogenic conditions in children early enough to prevent blindness with timely and appropriate treatment.

Cataract surgery and intraocular lens implantation in children.

As in the past, the current literature on childhood cataracts demonstrates the need for early diagnosis, surgical treatment that is quite different from adult cataract surgery, and prompt and adequate optical correction, as well as long-term and conscientious amblyopia therapy in cases of uniocular cataract. The choice of optical correction continues to generate controversy. Contact lenses, intraocular lenses, and epikeratophakia all have their advocates. Although contact lenses are still the most common option, interest in using intraocular lenses in children has grown. Over the past year, however, two disturbing reports of complications due to intraocular lens implants were published. Treatment of childhood cataracts remains more challenging than treatment of cataracts in adults, and indications for particular approaches to optical rehabilitation in the pediatric population continue to evolve.

The correction of unilateral aphakia in children treated for orbital rhabdomyosarcoma.

The survival rate of children with localized orbital rhabdomyosarcoma is now greater than 90% 3 years after diagnosis as a result of advances in radiation and chemotherapy. Ninety percent of these children develop cataracts within 1 to 4 years after the completion of radiotherapy. The correction of aphakia in these children is complicated by the concurrent keratoconjunctivitis and dryness associated with radiotherapy. Three patients with a diagnosis of orbital rhabdomyosarcoma underwent treatment for uniocular cataract. Two of the patients were unable to use extended wear contact lenses. Both underwent epikeratophakia with poor results. One patient who had clinically significant ocular drying prior to cataract extraction underwent successful implantation of an intraocular lens as a primary procedure, with excellent visual results. Clinicians should be aware of the difficulties associated with contact lens wear and epikeratophakia tissue lenses in children who have had high doses of radiation for orbital rhabdomyosarcoma. Such patients are probably best served by primary intraocular lens implantation or by preservation of the posterior capsule at the time of cataract extraction to allow secondary lens implantation if contact lens wear is unsuccessful.

Combined cataract extraction and epikeratophakia in children.

Nineteen children between the ages of 2 1/2 and 6 1/2 years who had cataracts not associated with trauma and who were judged to be poor candidates for contact lens wear underwent combined cataract extraction and epikeratophakia, followed by intensive amblyopia therapy. Follow-up ranged from 6 months to 7 years. In these monocularly aphakic children, three (16%) of the original 19 procedures failed and the tissue lenses were removed; two of these were repeated successfully. The success rate for the surgery was 86% (18/21) and 95% (18/19) for the patients. Postoperative visual acuity of 20/50 or better was achieved in six (33%) of the 18 patients with successful surgery. Another 11 (61%) achieved between 20/60 and 20/200. Postoperative astigmatism ranged between 0 and 4 diopters, with an average of 1.7 diopters. The results demonstrate that epikeratophakia can be successfully combined with cataract extraction in children with visually significant non-traumatic cataracts and that the majority of such children demonstrate an improvement in visual acuity.

Update on epikeratophakia in children.

Epikeratophakia continues to be an extremely attractive option for younger children with unilateral aphakia who are noncompliant users of contact lenses but who are young enough to benefit from amblyopia therapy. The epikeratophakia procedure is much safer than IOL implantation. The epikeratophakia tissue lens is especially useful for children with traumatic aphakia and corneal lacerations because the lens can strengthen and smooth the cornea as well as correct the aphakia. This allows much quicker rehabilitation than could be accomplished with contact lenses. The epikeratophakia procedure may be combined with a cataract extraction and should be in those children with acquired cataracts who demonstrate contact lens noncompliance in an office trial of contact lens insertion before operation. Epikeratophakia should be used with caution in neonates and young infants because of the rapid growth of the eye. Extended-wear contact lenses are a safer option for these children, and epikeratophakia can be performed as a secondary procedure if and when problems with contact lens compliance arise. Surface ocular problems such as uncontrolled dry eyes or severe blepharitis will continue to be incompatible with the survival of epikeratophakia tissue lenses. Children who are treated with high doses of radiation for orbital tumors such as rhabdomyosarcomas invariably develop radiation cataracts, which can occur before the onset of radiation keratitis. These children do not do well with epikeratophakia tissue lenses. Likewise, children with severe metabolic disturbances who are not healthy or gaining weight have a diminished chance of graft healing, as do children with poor vision in whom oculodigital autostimulation produces persistent epithelial defects, which prevent survival of the tissue lens.(ABSTRACT TRUNCATED AT 250 WORDS)

The nationwide study of epikeratophakia for aphakia in older children.

A nationwide study of epikeratophakia for aphakia in older children was conducted from March 1984 to March 1986. Sixty-three patients, 8 to 18 years of age, underwent this procedure in 65 eyes. Twenty-eight patients had congenital cataracts and 35 had traumatic cataracts. Fifty-one of the 65 eyes were aphakic at the time of surgery (secondary procedures). All surgeries were successful; no tissue lenses were lost or removed. Postoperatively, 73% of the patients were within 3 diopters (D) of emmetropia. The patients with congenital cataracts gained an average of one Snellen line of best-corrected visual acuity; patients with traumatic cataracts lost an average of one Snellen line of best-corrected visual acuity. In older pediatric patients, epikeratophakia appears to be a safe and effective procedure for the correction of aphakia.

Prediction of aphakic refractive error in children.

Formulas created to predict the optical requirements of the aphakic eye have been tested mainly in adult eyes. The accuracy of these formulas in shorter pediatric aphakic eyes was examined using retrospective analysis of 17 aphakic pediatric patients. The Sanders-Retzlaff-Kraff contact lens formula, used previously to predict required lens powers for epikeratophakia, consistently underestimated the required aphakic correction in the shorter eyes, which may have been responsible in part for the large undercorrections obtained previously in patients under one year of age. The Hoffer-Colenbrander and Binkhorst theoretical formulas, Donzis-Kastl-Gordon percentage change formula, and a linear regression formula derived from the present data (LIN), were significantly more accurate. The differences between these formulas were not significant. The use of one of these formulas should facilitate prediction of required epikeratophakia lenticule power or intraocular lens power in young children.

The nationwide study of epikeratophakia for aphakia in adults.

In the nationwide study of epikeratophakia, 154 ophthalmic surgeons who had attended a training course performed 519 procedures for the correction of aphakia in adults: 310 of the eyes had 30 or more days of follow-up after suture removal. Of 229 eyes, 172 (75%) were within 3 diopters of emmetropia after surgery. Of 259 eyes, 245 (95%) demonstrated improved uncorrected visual acuity; 138 (53%) improved by four or more Snellen lines. Of 265 eyes, 209 (78%) achieved within two lines or improved their best corrected visual acuity. Of the 119 patients who achieved or improved their preoperative best corrected visual acuity, 110 (92%) were within two Snellen lines or better by 30 to 60 days after suture removal. Of the 127 patients with more than three months of follow-up after suture removal, 124 (98%) of those between 18 and 70 years of age but only 13 of 23 (54%) of those between 81 and 87 years of age achieved within two lines or better of their best corrected visual acuity. Corneal astigmatism measured by keratometry changed from a preoperative mean (+/- S.D.) of 2.1 +/- 1.8 diopters to a postoperative mean of 2.7 +/- 2.6 diopters. Of the 519 tissue lenses, 22 (4%) were removed, and one third of these patients underwent a second, successful epikeratophakia procedure.

The nationwide study of epikeratophakia for aphakia in children.

In the nationwide study of epikeratophakia, 97 surgeons performed a total of 335 procedures in 314 eyes for the correction of aphakia in children under the age of 8 years 1 month. Fifteen children underwent bilateral surgery. Thirty-six tissue lenses were removed and 21 of these eyes underwent a second epikeratophakia procedure. Overall, the success rate for procedures was 89%, and with repeated surgery it was 95% for eyes. Seventy-three percent of the patients were within 3 diopters of emmetropia after surgery. Visual acuity results in patients able to provide verbal responses to the illiterate E, Allen card, or Snellen line chart testing showed improvement in most cases. The safety of epikeratophakia makes it a desirable option for the correction of aphakia in children who are spectacle or contact-lens intolerant, and the permanence of the correction eliminates the problem of optical noncompliance.

The nationwide study of epikeratophakia for myopia.

In the nationwide study of epikeratophakia, 116 ophthalmic surgeons performed 352 procedures for the correction of myopia; 256 of the eyes had 30 or more days of follow-up after suture removal. Of 204 eyes, 153 (75%) were within 30% of emmetropia after surgery. Of 208 eyes, 202 (97%) had postoperative best corrected visual acuity within two Snellen lines or better of their preoperative visual acuity. All but one patient improved uncorrected visual acuity. Of the 120 patients who equaled or improved their preoperative best corrected visual acuity, 116 (97%) were within two Snellen lines of their preoperative measurement between 30 and 60 days after suture removal. Corneal astigmatism changed from a preoperative mean (+/- S.D.) of 1.4 +/- 0.8 diopters to a postoperative mean of 2.6 +/- 2.1 diopters. Of 352 tissue lenses, 36 (10%) were removed, largely as a result of inaccurate power, decay, or failure to reepithelialize, and 17 of these eyes underwent a second successful epikeratophakia procedure.

Secondary cataracts in infants after lensectomies.

Three infants, one who was two weeks old, and two who were two months old, underwent lensectomy and vitrectomy in a total of four eyes for congenital cataracts by means of an automated suction cutter. Two patients with unilateral opacities underwent combined cataract extraction and epikeratophakia, and one with bilateral congenital cataracts underwent cataract extractions and was fit with extended wear contact lenses. In all cases, the surgery involved at least a 5-mm posterior capsulotomy with a shallow anterior vitrectomy, and was uneventful. Three of the four eyes developed new opacities that required surgical removal three to five months after the original surgery. Cytological evaluation of the specimen obtained from one patient showed this material to be lens epithelium. In all three cases, the material grew without the support of the posterior capsule; in one patient the material appeared to have seeded onto the iris. This previously unreported complication in infants with congenital cataracts who have undergone posterior capsulotomy and anterior vitrectomy emphasizes the need for frequent retinoscopies on such patients. The absence of the posterior capsule does not guarantee that these children will not develop secondary growth of lens epithelium which may obstruct the visual axis.

Interface opacities in epikeratophakia.

Although small, peripheral, cystic, or putty-gray infiltrates were observed along the suture tracks in 20 of 100 pediatric patients after epikeratophakia at Louisiana State University Medical Center, New Orleans, they progressed to clinically significant opacities in only three. In one, the interface material was curetted and the lenticule was reattached. The removed material was identified histologically as epithelial cells in varying states of degeneration. In a second case, the graft became hazy and the opacity involved most of the interface. The lenticule was removed, and epikeratophakia was again performed. On the posterior surface of the removed lenticule was a multilayered epithelium that had infiltrated into adjacent stromal lamellae. In the third case, a clear cyst resolved without intervention over a five-year period. These cases illustrate the importance of meticulous removal of all surface epithelium and the necessity for copious irrigation of epithelial debris intraoperatively. Epithelial ingrowth should not be confused with bacterial infection. Such opacities can be treated by curettage or aspiration of the invading material or removal of the epikeratophakia lenticule if spontaneous resolution does not occur.

Long-term follow-up of refractive and keratometric results of pediatric epikeratophakia.

To examine the long-term stability of epikeratophakia and its effect on the development of young eyes, the change in corneal curvature and refractive error over time were reviewed in pediatric patients who underwent epikeratophakia for optical correction of aphakia. Over an average follow-up time of 28.0 months, corneal curvature flattened by 1.15 diopters, or 0.53 D/yr. The average change in refractive error was -2.81 D over 23.6 months, or 1.49 D/yr. Patients younger than 1 year of age at surgery became significantly more myopic over the period of follow-up (4.75 D) than patients older than 1 year of age at surgery (2.24 D). These changes are consistent with the corneal flattening and increase in axial length expected from normal growth. Aphakic infants corrected to emmetropia with epikeratophakia will likely require correction of myopia in later childhood.

Epikeratophakia in children with traumatic cataracts.

Epikeratophakia provides a permanent optical correction for aphakia in children with congenital or traumatic cataracts; suturing the epikeratophakia graft onto the cornea eliminates the problems of contact lens or spectacle non-compliance in these young and generally uncooperative patients and provides tectonic support to scarred and irregular corneas. Eighteen children under the age of six years underwent epikeratophakia for the correction of aphakia after the removal of trauma-induced cataracts. Graft success rate was 88%; the average change in keratometry in the patients with successful grafts was 14.82 +/- 2.0 diopters. In the 13 patients eligible for visual acuity tabulation, preoperative acuities ranged from light perception to 20/200, and postoperative acuities ranged from hand motions to 20/30. Ten (77%) had acuities of 20/80 or better. Poor results in three patients with less than 20/200 acuities were likely the results of non-compliance with amblyopia therapy. Present work indicates that in cases of traumatic cataract, the epikeratophakia procedure facilitates amblyopia therapy and decreases the astigmatism in scarred and irregular corneas.

Five year follow-up of epikeratophakia in children.

Epikeratophakia alters the anterior curvature of the cornea by the addition of a machine-carved donor lenticule. Since March 1980, 88 patients under eight years of age have had epikeratophakia, with at least six months of follow-up. Eighty percent of the original surgeries were successful; some failed grafts were replaced successfully, so that in all, 89% of the patients had successful grafts. The average increase in curvature of the cornea was 14.7 diopters, and the average spectacle overcorrection was +0.56 diopters. In these growing eyes, we documented a myopic shift of 1.5 diopters per year. Visual acuity results varied with the timing of refractive surgery, density of the amblyopia, and the parents' ability to maintain the patching schedule. The largest group of children were those who had unilateral traumatic cataracts. In this group, 7 of 15 patients who had surgery under 4 years of age had final verbal acuities of 20/40 or better. Long-term follow-up has demonstrated that epikeratophakia safely and successfully corrects refractive errors in aphakic children either as a primary procedure, or as a secondary procedure after cataract extraction.

Epikeratophakia in children.

Epikeratophakia was performed in 61 children for the correction of aphakia after the removal of unilateral congenital or traumatic cataracts; 51 patients (54 grafts) have more than 6 months follow-up. In the first 27 grafts, 8 (30%) failed, but in the last 27 grafts, only 2 (7%) failed, largely due to improved surgical and tissue handling techniques. The average increase in corneal refractive power for the early patients was 12.68 +/- 4.63 D with an average overrefraction of +0.45 +/- 5.60 D. The last half of the patients showed an average increase of 14.83 +/- 4.83 D, with an average overrefraction of -0.00 +/- 5.20 D. Visual acuity results in patients with traumatic cataracts have been the most satisfactory, with the majority of patients obtaining useful vision. It also appears that in patients with congenital cataracts, the younger the patient at the time of surgery, the greater the chance for a good visual result. Some improvement in vision has been seen in all of the children with successful grafts, even those beyond the age when amblyopia therapy would be considered to have some potential for therapeutic effect. By attaching the correction permanently on the eye, epikeratophakia facilitates the vigorous occlusion therapy required after cataract extraction in these children.

Oral fluorescein angioscopy in aphakic children.

Seven children who had undergone removal of congenital cataracts were evaluated postoperatively for cystoid macular edema during outpatient visits. Fluorescein was administered orally in a fruit juice cocktail, and the eyes examined by angioscopy 10-20 minutes and 45-60 minutes after dye ingestion. No evidence of macular leakage was observed in any of the 11 eyes examined. It appears that this diagnostic procedure is feasible in young patients, and that the incidence of cystoid macular edema after congenital cataract extraction may be less than has been previously reported.

Preliminary visual results of pediatric epikeratophakia.

Although cataract surgery is feasible in children with unilateral cataracts, visual rehabilitation depends on optical correction and conscientiously maintained amblyopia therapy. Epikeratophakia for the correction of aphakia was performed in 47 children (50 grafts). Postoperative keratometry readings showed an average increase of 12.68 diopters in early patients. With new tissue-handling techniques, the last eight patients showed an average increase of +16.80 D, with -0.64-D overrefraction for emmetropia. Visual results indicate that epikeratophakia is an effective primary procedure for patients with unilateral traumatic cataracts and that it is superior to leaving vision uncorrected in children who have had unilateral congenital cataracts removed and are contact-lens intolerant. Further studies with younger patients will be necessary to define its role in neonates; however, individual results demonstrate that good vision is obtainable with epikeratophakia.