The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

["Fragebogen zum Kindlichen Sehvermögen (FKS)". Assessment of quality of life with the German version of the Children's Visual Function Questionnaire]. / Fragebogen zum Kindlichen Sehvermögen (FKS). Die deutsche Version des "Children's Visual Function Questionnaire"--ein Instrument zur Erfassung der Lebensqualität sehbeeinträchtigter Kinder.

BACKGROUND: The assessment of quality of life plays an increasing role in ophthalmology. Standardized questionnaires such as the National Eye Institute Visual Function Questionnaire (NEI-VFQ) are useful instruments to evaluate the impact of ophthalmological diseases on the quality of life in adults. In children and infants, different instruments are needed, partly because of the changing developmental stages with age. Felius and colleagues developed a questionnaire to assess the quality of life in young children with visual impairment, the Children's Visual Function Questionnaire (CVFQ). It was validated in the United States. Our aim was to translate and adapt the questionnaire to make it applicable for the German-speaking countries. METHODS: Two independent groups in the ophthalmology departments of the University of Frankfurt and the University of Freiburg translated the questionnaire into German. In cooperation with the authors of the CVFQ, a consensus adaptation was created, which was then reexamined by the two German groups to establish the adaptation presented here. RESULTS: The German adaptation, like the original instrument, exists in two versions, one for infants and children <3 years of age and one for children > or =3 years. Besides vision and general health, the questionnaire assesses the following quality-of-life domains: competence, personality, family impact, and treatment. The first data for patients with an ophthalmological diagnosis (amblyopia and occlusion treatment, and aphakia with contact lens treatment) were collected and compared with data of children without visual impairment. CONCLUSION: The translated CVFQ provides an instrument for those in German-speaking countries to assess the quality of life in visually impaired children. The data sample shows its applicability for assessing the influence of diseases of the visual system and their treatment on the patients' and families' lives.

Re-recession of the medial rectus muscles in patients with recurrent esotropia.

PURPOSE: Retrospective evaluation of changes in ocular motility after surgical re-recession of the medial rectus (MR) muscles as treatment of recurrent esotropia (ET). METHODS: We describe 115 patients (age, 11 months-77 years; median, 11.1 years; 83 children and 32 adults) with an average amount of non-accommodative ET before surgery of 18.7 PD (SD = 8.8 PD). Preoperative alignment, amount of re-recession, distance from insertion to the limbus, and postoperative alignment and versions were collected. RESULTS: In most cases, MR muscles were re-recessed to a fixed distance of 12 mm from the limbus, with unilateral re-recessions in cases with relatively small ET (typically < 20 PD) and bilateral re-recessions in cases with larger amounts of ET (typically > 20 PD). No clear relation was found between the amount of re-recession and the change in alignment in prism diopters. The success rate (esotropia [ET] < or = 10 PD or exotropia [XT] < or = 8 PD) 4 weeks to 8 months after surgery was 85%, with 4 patients still showing ET and 13 patients showing XT. Incidence of XT was higher for bilateral than for unilateral re- recessions. Significant underaction of the MR muscles was noted in 7% of the patients. None of the undercorrected patients and only 1 of the overcorrected patients were adults. Among adults, incidence of MR underaction was 4%. Long-term follow-up (8-120 months; median, 25 months) data from 59 patients indicated that good stability in alignment can be expected. CONCLUSION: The results support the notion that MR re-recession to 12 mm from the limbus successfully corrects recurrent ET up to 35 PD and that it is particularly effective in adults.

Effect of stimulus size on static visual fields in patients with retinitis pigmentosa.

PURPOSE: To determine the effect of stimulus size on sensitivity of patients with retinitis pigmentosa (RP) as measured by automated static perimetry. DESIGN: Comparative case series. PARTICIPANTS: Thirty-nine patients with RP and a control group of 10 healthy volunteers. METHODS: Automated static perimetry (full threshold programs 24-2 or 30-2) was performed twice on one eye of each participant using stimulus sizes III (0.43 degrees diameter) and V (1.72 degrees diameter). Data from the same 50 test locations were used from each field. MAIN OUTCOME MEASURES: At each location, for each participant, the size effect was computed as the difference (in decibels) in sensitivities for sizes V and III, and the average sensitivity was computed as the mean of sensitivities for the two sizes. RESULTS: For both patient and control groups, the size effect was negatively correlated with average sensitivity (r(2) > 0.124; P: < 0.001). The mean size effect was significantly greater for the patient group than for the control group: 8.6 (+/- 3.6) dB versus 5. 4 (+/- 2.2) dB (t = 18.0; P: < 0.001). The percentage of abnormal locations (more than 8 dB below mean normal) tended to be lower for size V than for size III, with a mean of 67% for size V versus 95% for size III. The percentage of absolute defects was also lower for size V than for size III, with a mean of 35% for size V versus 54% for size III. CONCLUSIONS: In damaged regions of the visual fields of patients with RP, increase in stimulus size from III to V can produce abnormally large increases in perimetric sensitivity. Size III may be more useful than size V for detection of field abnormality, whereas size V may be more useful than size III for observing progression of advanced RP.

Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy.

Blue cone monochromacy (BCM) is an X-linked ocular disease characterized by poor visual acuity, nystagmus, and photodysphoria in males with severely reduced color discrimination. Deletions, rearrangements and point mutations in the red and green pigment genes have been implicated in causing BCM. We assessed the spectrum of genetic alterations in ten families with BCM by Southern blot, polymerase chain reaction, and sequencing analysis, and the phenotype was characterized by ophthalmoscopy, fluorescein angiography, and a battery of tests to assess color vision in addition to routine ophthalmological examination. All families showed clinical features associated with BCM. Acuities were reduced in all affected males, and photopic b-wave was reduced by more than 90% in seven families. In three families, however, the photopic b-wave response showed uncharacteristic relative preservation of 30-80% (of the clinical low-normal value). The color vision was unusually preserved in two affected males, but this was not correlated with photopic electroretinography retention. Progressive macular atrophy was observed in affected members of two BCM families while the rest of the families presented with normal fundus. In nine families deletions were identified in the gene encoding the red-sensitive photopigment and/or in the region up to 17.8 kb upstream of the red gene which contains the locus control region and other regulatory sequences. In the same nine families the red pigment gene showed a range of deletions from the loss of a single exon to loss of the complete red gene. In one family no mutation was found in the exons of the red gene or the locus control region but showed loss of the complete green gene. No association was observed between the phenotypes and genotypes in these families.

Photopic temporal processing in retinitis pigmentosa.

PURPOSE: The relation between early changes in the photopic flicker electroretinogram (ERG) and photopic psychophysical changes in retinitis pigmentosa (RP) is poorly understood. Here, abnormalities in foveal and extrafoveal temporal contrast sensitivity functions (TCSFs) were studied in a group of carefully selected patients with RP who had relatively preserved macular function. The psychophysical results were compared with changes in the timing of the multifocal ERG. METHODS: Subjects were patients with RP who had acuity > or =20/32 and no visual field defects within 6 degrees from the fovea. Maxwellian-view and direct-view optical systems were used to obtain foveal and extrafoveal TCSFs under a range of test conditions, including high retinal illuminances that yielded temporal contrast sensitivity independent of mean retinal illuminance. TCSFs were described using log sensitivity and corner frequency parameters. RESULTS: Foveal TCSFs in these patients showed overall reductions in sensitivity but no frequency-dependent defects. Also, no macular defects were found in the timing of the multifocal ERG. TCSFs from extrafoveal locations in moderate field defects, obtained at retinal illuminances that were sufficient to render flicker sensitivity independent of effective mean luminance, showed reductions in overall sensitivity as well as changes in temporal tuning. The multifocal ERGs from these extrafoveal locations showed signs of temporal slowing. CONCLUSIONS: Changes in temporal tuning (both psychophysical and electroretinographic) were found only within visual field scotomas, whereas changes of the log sensitivity parameter were found also in the relatively preserved foveas of this group of patients with early stage RP.

Bilateral macular atrophy in blue cone monochromacy (BCM) with loss of the locus control region (LCR) and part of the red pigment gene.

PURPOSE: To describe unusual macular abnormalities in a family with blue cone monochromacy (BCM, or X-linked incomplete achromatopsia) and deletion of about 9.5 kb comprising part of the red pigment gene and the region upstream of the red pigment gene. METHODS: The molecular structure of the red and green pigment genes and the locus control region (LCR) upstream of the red gene were studied for deletions, rearrangements and point mutations by Southern blot analysis and PCR. Four affected males (ages 33, 45, 51, and 59) and a carrier female (age 58) were examined by funduscopy and fluorescein angiography. Extensive color vision testing as well as rod and cone electroretinography (ERG) were performed on two of them. RESULTS: Analysis showed that the 6 kb proximal red gene region, exon 1 and about 3.1 kb of intron 1 of the red gene are deleted in this family. Exons 2-6 of the red gene, all the exons of the green gene and the Tex 28 gene were present. Four affected males had bilateral macular changes, including three with overt atrophy. All had visual acuity of 20/200 and their color vision was typical for BCM, with the absence of long- and middle-wavelength sensitive cone function. The ERG showed normal rod responses, whereas the photopic cone and 30-Hz flicker responses were >95% reduced. CONCLUSIONS: We report the unusual association between macular atrophy and BCM resulting from the loss of an approximately 9.5 kb region encompassing the LCR, proximal red gene promoter elements and exon 1 of the red gene. However, loss of the LCR and promoter is not sufficient to explain the phenotype since we have observed other BCM families with similar deletions who do not exhibit macular changes.

Functional characteristics of blue-on-yellow perimetric thresholds in glaucoma.

PURPOSE: Blue-on-yellow (B-on-Y) perimetry assesses the S-cone visual field under yellow adaptation. Glaucomatous field defects have been shown to appear earlier and to be larger in B-on-Y perimetry than in standard perimetry. An upper limit to the use of B-on-Y perimetry is set by the separation of the S-cones from the M- and L-cones. But, because the S-cones may also input to the luminance channel, the actual separation of the color and luminance channels is unknown. Here, the relative sensitivities of the color and luminance channels under B-on-Y test conditions are measured. METHODS: In 15 eyes with early glaucoma, 19 risk eyes, and 10 normal eyes, B-on-Y thresholds were measured from 0 degrees to 20 degrees eccentric and were compared to pure chromatic (B-in-Y) and achromatic (Y-on-Y) thresholds, obtained under identical yellow adaptation. RESULTS: In normals, B-on-Y thresholds were found to coincide with B-in-Y thresholds; Y-on-Y values were 0.5 log (at 20 degrees) to 0.9 log (at 0 degrees) higher. In the pathologic groups, the differences between B-in-Y and Y-on-Y thresholds were smaller. Pathologic threshold elevation is on average 1.8 times larger for chromatic than for achromatic stimuli. In some cases, the luminance channel takes over detection of the B-on-Y stimulus. CONCLUSIONS: In normals, the B-on-Y stimulus is mediated by the color channel. Takeover of detection by the luminance channel might impose limits on following color defects with B-on-Y perimetry. This takeover may occur before the S-cones become less sensitive than the M- and L-cones and might indicate S-cone input to the luminance channel.

Peripheral cone contrast sensitivity in glaucoma.

Colour vision tests for detection of glaucomatous damage frequently suffer from two problems: most tests are confined to foveal vision, whereas defects tend to appear first extrafoveally; and the modulation directions in colour space are not optimal. This paper deals with peripheral testing à la Yu, Falcao-Reis, Spileers and Arden [(1991) Investigative Ophthalmology and Visual Science, 32, 2779-2789], and investigates whether there are modulation directions that show preferential sensitivity reduction in glaucoma. In 14 eyes with early glaucoma, 17 risk eyes and 10 normals, 12 deg peripheral colour contrast thresholds were determined for L, M, S, L-M and L+M test directions. Threshold elevations were correlated in all test directions, with S modulation yielding the largest elevations.

Relationship between spectral transmittance and slit lamp color of human lenses.

PURPOSE: To study the relationship between subjective lens color as observed with slit lamp biomicroscopy and spectral transmittance of the lens. To propose a model for this relationship to derive quantitative information on lens pigmentation from slit lamp observation. METHODS: Twenty-nine normal lenses, from donors aged 14 to 86 years, were used. The fraction of light transmitted from a narrow beam was measured as function of wavelength. The spectra were fitted with the one-parameter TL model of Pokorny et al. The relationship between this parameter and the color grading from Chylack et al. (lens opacity classification system III nuclear color score) was established. RESULTS: After slight adaptation of the TL model, the shapes of the transmittance spectra corresponded closely to the TL model (average residual error 0.05 log units). Log transmittance and lens opacity classification system nuclear color score were closely related (r = 0.90, 0.77, and 0.55 for 400, 500, and 602 nm, respectively). CONCLUSIONS: A mathematical relationship between TL parameter and lens opacity classification system nuclear color score could be established to predict lens transmittance from lens opacity classification system nuclear color score. This relationship was successful in predicting the correction for lens absorption needed in blue-on-yellow perimetry.

Oculokinetic perimetry compared with standard perimetric threshold testing.

To calibrate oculokinetic perimetry (OKP) as developed by Damato in terms of conventional perimetric threshold values, 33 eyes with either glaucoma or ocular hypertension were tested with a standard Humphrey Field Analyzer using the Central 30-2 test and twice with a 26-point OKP chart. The frequency of seeing of the OKP test spot was plotted against 30-2 thresholds. This showed a weak relation between the two tests. Subsequently eyes that were considered to have had poor fixation were omitted, but false positive and false negative results still occurred in 19 remaining eyes. To check whether Troxler's effect (local adaptation) might have caused false positives, 6 subjects were tested with OKP, controlling the fixation times. Increasing the fixation time from 'very short' to 2 and 5 seconds yielded more 'not seen' responses in OKP. False negative data were found to occur preferentially in border areas of visual defects. The average frequency of seeing curve over all data showed a 50% frequency of seeing for the OKP stimulus at a 14.6 dB equivalent conventional threshold value. The spreading of the curve was 7 dB (95% confidence interval 28 dB).

Discrepancies between single stimulus and multiple stimulus visual field examinations with the Peritest semi-automated perimeter in glaucoma patients.

In a total of 24 randomly selected eyes of glaucoma patients, tested with the automated (single stimulus) and the manual (multiple stimulus) modes of the semi-automated Peritest perimeter, the numbers and depths of defects were compared as estimated with these two different measurement strategies. It was found that with the manual technique considerably less defects were detected than with the automated strategy.