Remote image based retinopathy of prematurity diagnosis: a receiver operating characteristic analysis of accuracy.

BACKGROUND/AIMS: Telemedicine offers potential to improve the accessibility and quality of diagnosis of retinopathy of prematurity (ROP). The aim of this study was to measure accuracy of remote image based ROP diagnosis by three readers using receiver operating characteristic (ROC) analysis. METHODS: 64 hospitalised infants who met ROP examination criteria underwent two consecutive bedside procedures: dilated examination by an experienced paediatric ophthalmologist and digital retinal imaging with a commercially available wide angle camera. 410 images from 163 eyes were reviewed independently by three trained ophthalmologist readers, who classified each eye into one of four categories: no ROP, mild ROP, type 2 prethreshold ROP, or ROP requiring treatment. Sensitivity and specificity for detection of mild or worse ROP, type 2 prethreshold or worse ROP, and ROP requiring treatment were determined, compared to a reference standard of dilated ophthalmoscopy. ROC curves were generated by calculating values for each reader at three diagnostic cut-off levels: mild or worse ROP (that is, reader was asked whether image sets represented mild or worse ROP), type 2 prethreshold or worse ROP (that is, reader was asked whether image sets represented type 2 prethreshold or worse ROP), and ROP requiring treatment. RESULTS: Areas under ROC curves ranged from 0.747-0.896 for detection of mild or worse ROP, 0.905-0.946 for detection of type 2 prethreshold or worse ROP, and 0.941-0.968 for detection of ROP requiring treatment. CONCLUSIONS: Remote interpretation is highly accurate among multiple readers for the detection of ROP requiring treatment, but less so for detection of mild or worse ROP.

Neuronal ceroid lipofuscinosis. Diagnosis by semithin plastic-embedded sections of peripheral blood lymphocytes from a patient with a normal blood smear.

Neuronal ceroid lipofuscinosis is an important diagnostic consideration in a school-aged child with progressive blindness. Neurologic symptoms and signs may appear late, and the retinopathy is not specific. Ultrastructural abnormalities have been demonstrated in many body tissues, but skin has been claimed to be the most reliable. Light and electron microscopic examinations of WBCs have also been helpful in several instances. In the case reported, the skin biopsy specimen and light microscopy of a peripheral blood buffy coat failed to disclose diagnostic changes. Examination of semithin sections of plastic-embedded peripheral blood provided the answer.

Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective.

Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.

Amblyopic eyes have longer reaction times.

The RT (reaction time) to a 0.25 degree spot of light was measured monocularly on 25 normal subjects and 36 strabismic patients. The overall mean RT and the delta RT (difference in RT between the right and left eyes) for the 19 strabismic patients without amblyopia did not differ significantly from that of the normal subjects. The overall mean RT of the dominant eyes of the 17 amblyopic patients did not differ significantly from that of either the faster of slower eyes of the normal subjects. The overall mean RT of the amblyopic eyes was significantly longer than that of the normal subjects. The delta RT was significantly larger in the amblyopic patients. A regression analysis of the visual acuity of the amblyopic eye and the delta RT showed that the data was best fit by a linear equation. The coefficient of correlation was +0.82. Additional experiments showed that the longer Rt of the amblyopic eyes was not caused by eccentric fixation or by the reduced visual acuity.

Stereo-discrimination between diplopic images in clinically normal observers.

When retinal disparity exceeds the limits for fusion, the resulting images are perceived as diplopic. In a stereo test that allowed comparison of crossed and uncrossed disparity sensitivities, 74% of the subjects perceived convergent disparities more readily than divergent disparities. This asymmetric sensitivity to disparity did not appear to be related to measurements of phoria, vergence amplitudes, or clinical measurements of stereo acuity.

Acuity card assessment of visual function in the cryotherapy for retinopathy of prematurity trial.

The primary outcome measure of the effectiveness of cryotherapy in the original design of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was the anatomic status of the retina, as documented by fundus photography 3 months and 12 months after infants had received treatment. The authors describe the addition of a measurement of visual function, the Acuity Card procedure, to the CRYO-ROP study. After training, four visual-acuity testers attempted to measure monocular grating acuity in all randomized infants and approximately one fourth of the natural-history infants in the study, tested at 1 year postcryotherapy or 1 year postterm. In 95% of infants on whom testing was attempted, monocular acuity values from each eye were obtained. Interobserver test-retest results on 25 eyes of 13 randomized infants agreed to within one octave or better in all but one of the eyes. The high testability rate and good interobserver agreement suggest that the Acuity Card procedure has been a successful method of assessing visual function in the CRYO-ROP study.

The nystagmus blockage syndrome. Congenital nystagmus, manifest latent nystagmus, or both?

We have carefully studied, by quantitative oculography, a patient with the nystagmus blockage syndrome (NBS), and two patients with a similar disorder of eye movements that might be mistaken clinically for NBS. Our recordings revealed two distinctly different abnormalities present in a single patient with NBS. Our NBS patient exhibited congenital nystagmus (CN) waveforms when viewing at distance; the CN did not damp with convergence on a near target. When the patient allowed one eye to become esotropic, however, the nystagmus damped considerably and abruptly changed from CN to manifest latent nystagmus (MLN). This peculiar transition from CN to MLN has not been described previously. The appearance of MLN in a case with ongoing CN suggests that two different mechanisms may underlie NBS, since the only other case documented with eye movement recordings showed no transition to MLN. Because the diagnosis of NBS usually is made on evidence of clinical signs alone, it is probable that these two types have been combined indiscriminately and presented as one syndrome. In addition, our discovery of two mechanisms discernable only by quantitative recording suggests that NBS has been diagnosed inappropriately in patients with clinically similar but oculographically different eye signs. Further quantitative studies are required to fully define NBS and to determine if these are the only two mechanisms found in this syndrome.

Renal transplantation after Streptococcus pneumoniae-associated hemolytic uremic syndrome.

Of the several causes of nondiarrheal hemolytic uremic syndrome (HUS), infection with Streptococcus pneumoniae is infrequent, but important, because of its unique pathogenesis. A comprehensive literature review found 37 well-documented cases of S pneumoniae-associated HUS (SP-HUS), only 2 of which progressed to end-stage renal disease (ESRD). We report the third such child, and the first to receive a renal transplant following SP-HUS. Her course illustrates several unique characteristics of SP-HUS common to previous patients reported in the literature, including a greater duration of oligoanuria compared with cases not progressing to ESRD, the significant adverse effect of unwashed blood products, and a possible influence of female gender on outcome. Clinicians caring for children with SP-HUS should be aware of these differences and modify therapy appropriately to avoid known risk factors for poor outcome, specifically the use of unwashed blood products.

Hemodialysis followed by continuous hemofiltration for treatment of lithium intoxication in children.

Hemodialysis is the usual recommended treatment for severe lithium intoxication; however, rebound of lithium levels may require repeated hemodialysis treatments. We proposed that the addition of continuous hemofiltration after hemodialysis would prevent rebound by providing ongoing clearance of lithium. We report two pediatric patients with lithium intoxication treated by hemodialysis followed by continuous venovenous hemofiltration with dialysis (CVVHD). Both patients were symptomatic at presentation and had initial lithium levels more than three times the usual therapeutic range. Hemodialysis followed by CVVHD resulted in rapid resolution of symptoms, followed by continuous clearance of lithium without requiring repeated hemodialysis sessions. Both patients had return of normal mental status during CVVHD treatment, and neither patient experienced complications of hemodialysis or CVVHD. Total duration of treatment with hemodialysis followed by CVVHD was 34.5 hours for the first patient and 26 hours for the second patient. We conclude that hemodialysis followed by CVVHD is a safe and effective approach to the management of lithium intoxication in children.

Lipopolysaccharide induces time-dependent increases in prostaglandin H synthase-2 and cytosolic phospholipase A2 mRNA in cultured human microvessel-derived endothelial cells.

The effect of lipopolysaccharide (LPS) upon the cellular content of mRNA for several enzymes associated with the arachidonic acid cascade was determined in human microvessel-derived endothelial cells. Cells were treated with either vehicle or 10 ng/mL LPS for up to 24 h. Reverse transcription followed by DNA amplification and Southern blotting were used to quantify mRNA for prostaglandin H synthase-1, prostaglandin H synthase-2, cytoplasmic PLA2, and a group II secretory PLA2. LPS treatment resulted in an increase in prostaglandin H synthase-2 mRNA after 4 h with a second peak occurring at 12 h of incubation. The expression of prostaglandin H synthase-1 mRNA was not altered by LPS treatment. An increase in cytoplasmic PLA2 mRNA but not group II PLA2 mRNA was seen after 12 h. These data demonstrate that LPS can increase mRNA production for the inducible form of prostaglandin H synthase and for cytoplasmic PLA2 in a time-dependent manner in human microvessel-derived endothelial cells. These multiple, specific increases in the prostaglandin H synthase-2 and phospholipase A2 mRNA values suggest a complex interaction between bacterial LPS and the endothelial cell eicosanoid system.

Establishment and characterization of a line of adipose-derived human microvascular endothelial cells (HADMEC-5) transformed by simian virus 40 large T antigen expression: application to endotoxin research.

This paper reports the establishment and initial characterization of an immortalized line of human, adipose tissue-derived microvascular endothelial cells. Transfection of primary endothelial cell cultures was accomplished by the introduction of a plasmid, which contained simian virus 40 large T antigen DNA as well as a Rous sarcoma viral promoter region. One emergent colony, termed HADMEC-5, was isolated and has been passaged 45 times to date. The cells express simian virus 40 large T antigen protein, are immunohistochemically positive for factor VIII-related antigen, bind Ulex europaeus lectin, and accumulate Dil-labeled acetylated low density lipoprotein. The HADMEC-5 line demonstrates a highly proliferative growth rate in the absence of supplemental growth factors, when compared with primary cultures of nontransformed endothelial cells. HADMEC-5 growth remains serum dependent, but exhibits a lower serum requirement than nontransformed cells. The transformed cells grow well upon a variety of matrix compounds and in a variety of growth media. When grown upon Matrigel, the HADMEC-5 cells form three dimensional tube-like structures. The HADMEC-5 line was also tested for its ability to produce eicosanoids in response to bacterial lipopolysaccharide. The transformed cells, tested at passages 7 and 45, displayed a dose-dependent production of prostaglandin E2 in response to lipopolysaccharide in a manner similar to that seen in primary cell cultures. Threshold sensitivity to lipopolysaccharide was 10 pg/mL of media. The HADMEC-5 cell line represents a unique model in which to investigate lipopolysaccharide interactions with microvessel-derived endothelial cells and is of potential value in the study of other aspects of endothelial cell physiology.

Pathophysiology of ovine smoke inhalation injury treated with extracorporeal membrane oxygenation.

An ovine model was used to study the pathophysiology of smoke inhalation injury treated with extracorporeal membrane oxygenation (ECMO). Smoke inhalation is characterized by leukocyte-oxygen free-radical mediated acute lung injury. Treatment with ECMO was by extracorporeal venoarterial or venovenous perfusion using a venous drainage reservoir, roller pump, heat exchanger, and membrane lung oxygenator capable of oxygen delivery to and carbon dioxide removal from a patient. Blood-foreign surface interactions are known to occur during ECMO. We examined the effects of ECMO on circulating leukocytes, oxygen free-radical activity, thromboxane release, and gas exchange after smoke inhalation injury. Animals treated with smoke and ECMO had significantly increased circulating thromboxane B2 levels and oxygen free-radical activity compared with sham-treated animals and animals treated with smoke and mechanical ventilation (MV). Likewise, there was a significant increase in lung wet-to-dry weight ratios in animals treated with smoke and ECMO compared with those treated with smoke and MV. These data may account for the initial deterioration in native lung function after the initiation of ECMO and imply that ECMO may potentiate the pathophysiology of smoke inhalation injury.

Direct trauma to the superior oblique tendon following penetrating injuries of the upper eyelid.

We report two cases of direct trauma to the superior oblique tendon after penetrating injury of the upper eyelid with hook-shaped tools. Both patients originally presented with a Knapp type VII superior oblique palsy, but one patient severed the superior oblique tendon proximal to the trochlea, whereas the other patient engaged the distal reflected segment of the tendon with the hook and pulled it forward into the upper eyelid.

Maternal intrauterine herpes simplex virus infection leading to persistent fetal vasculature.

Herpes simplex virus can cause serious ocular and systemic disease in the neonate. The mode of transmission to the neonate is usually from the maternal birth canal to the fetus intrapartum; but much more rarely, hematogenous transplacental infection can affect the developing fetus months prior to birth. Persistent fetal vasculature occurs when there is persistence of the fetal ocular vasculature, which normally regresses prior to birth. To our knowledge, we report the first case of serologically proven intrauterine herpes simplex virus infection associated with bilateral persistent fetal vasculature in a surviving term infant. Arch Ophthalmol. 2000;118:837-840

Color perimetry.

Seven subjects were studied to determine the reproducibility of color isopters utilizing a Tubingen perimeter with targets equated for radiant energy and separate for heterochromatic flicker luminance. Achromatic threshold recognition of targets for equal luminance gave smaller isopters with longer wavelengths (red). Color recognition thresholds, on the other hand, showed large blue, midzone red and green, and small yellow isopters. The target recognition and color recognition thresholds for equal energy targets gave smaller red isopters. The data support Traquair's contention that all color isopters would be equivalent if hue, saturation, and intensity were equated. Clinically, the detection of subtle peripheral and central field defects might reside in the use of appropriately selected equally bright-colored targets.

Congenital nystagmus surgery. A quantitative evaluation of the effects.

Nystagmus intensities at various gaze angles were studied both preoperatively and postoperatively, using accurate ocular motility recordings, in three cases of congenital nystagmus. In addition to shifting the nystagmus null, the surgery broadened the null region and resulted in an overall reduction in nystagmus intensity at all gaze angles. Surgical rotation also resulted in improved visual acuity in all cases. The postoperative acuity at 0 degrees was better than the preoperative acuity at both 0 degrees and the patient's preferred gaze angle (ie, the preoperative null angle). This was not only for the two patients who showed an improved preoperative acuity with their head turn but also for the patient whose preoperative acuity did not substantially improve with her preferred head turn. Eye movement recordings have made it possible to accurately determine the amount of surgery required and to predict acuity increases even when undetectable during the preoperative clinical examination.

Herpes simplex retinitis.

Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed.

Paradoxical pupillary responses in congenital stationary night blindness.

Three unrelated boys, ages 2, 6, and 10 years, who have congenital stationary night blindness with myopia and a Schubert-Bornschein-type electroretinogram finding, were found to show a "paradoxical" pupillary constriction in darkness. When examining room lights are turned out, the patient's pupils briskly constrict and slowly dilate. Older night blind male relatives of these boys did not show this abnormal constriction to darkness.

Retrolental Fibroplasia. II. Pathologic correlation.

Retinas of 142 eyes from 71 premature infants on whom autopsies had been done were studied by gross observation and by using PAS-stained whole mount, trypsin-digest, and conventional histological techniques. With these techniques, vascular pathologic condition was correlated with fluorescein angiograms in living infants with acute retrolental fibroplasia. The specific lesions seen in acute phase were a major arteriovenous shunt in the eye, microvascular changes including tufting, and obliteration of capillaries around arteries and veins. Regression occurred by vascular budding from the anterior edge of the shunt. Observations on vascularization in the normal indicated a variability of the level of maturation of the retinal vasculature, only roughly correlated with gestational age.

The correlation of visual function with posterior retinal structure in severe retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity previously reported reduced incidence of both poor structural and functional outcomes after cryotherapy. We compared the results in 304 eyes of patients in the randomized portion of the trial in whom both structural and functional assessments were performed 12 months after randomization. Two hundred fifty-five eyes (83.9%) had concordant outcomes: 153 eyes had favorable structural and functional outcomes and 102 eyes had unfavorable structural and functional outcomes. Twenty-nine eyes (9.5%) had discordant outcomes: 20 eyes had favorable structural and unfavorable functional outcomes and nine eyes had unfavorable structural and favorable functional outcomes. The small number of discordant outcomes could generally be accounted for by three factors: (1) retinal abnormalities beyond those considered in the photographic grading system (12 eyes), (2) nonretinal visual pathway disease (five eyes), or (3) false-positive and false-negative results in the measurement systems used to evaluate structure and function (five eyes). In 20 eyes (6.6%), photographs could not be graded or the visual acuity was untestable. We conclude that the appearance of the posterior pole of the eye correlates well with grating acuity in the 12-month-old infant with a history of severe retinopathy of prematurity.