Purpose: Hemophagocytic syndrome (HS) is a rare disease with a spectrum of ocular findings. The authors report a unique funduscopic presentation of HS in a neonate and a discussion of diagnosis, typical features, management, and outcome. Methods: Single case report with retrospective analysis of the published literature of patients with HS and ocular findings from 1950 to present using the key terms hemophagocytic, lymphohistiocytosis, ocular, and ophthalmic. Literature search from 1950 to the present was performed through PubMed/MEDLINE and the Cochrane database. Requirement for inclusion was that the article or abstract was written in English. Results: A 4-week-old neonate with HS demonstrated bilateral discrete white dots within the retina, which resolved incompletely over the course of the next months but showed increased pigmentation. Conclusion: With so few documented ophthalmic cases of HS in existence, the ocular findings at this point can be seen as diverse and variable. However as more cases are reported, hopefully this will allow for increased recognition of the ophthalmic manifestations and sequelae and in turn lead to improved treatment of this disease.

was detected in 32 of 100 subjects. The sensitivity of the method was 56 (82.4%) of 68 and the specificity was 30 (93.8%) of 32. The PPV was 96.6%; NPV, 76.9%. Conclusions: The sensitivity of the method was low. The ROP that was missed was peripheral stage 1 or stage 2 disease in peripheral zone 2 or zone 3. This was largely due to the technical limitations of the speculum-camera interface preventing a better view of the periphery. The ROP cases that were missed by the photographic examination regressed spontaneously on follow-up. No disease more posterior to peripheral zone 2 was overlooked. These results detail the accuracy of the method employing the technique of photoscreening as a potential substitute for detailed ophthalmological examination. At present there are clear technical limitations to such a substitution. The study is part of an ongoing project to determine the feasibility of employing neonatal nurses trained to take digitized images of the premature infant’s retina and telemeter the results to be read by an experienced ophthalmologist remote from the site. Arch Ophthalmol. 2001;119:268-272

Purpose: Plus disease is defined as arteriolar tortuosity and venous dilation greater than that of a standard published photograph. This study examines the tortuosity of arterioles in this image using computer-based image analysis, and compares these values to expert interpretations of an independent set of retinal images.

PURPOSE: To examine the relationship between rate of vascular change and plus disease diagnosis.DESIGN: Retrospective observational case-control study.METHODS: Wide-angle images were taken bilaterally from 37 infants at 31 to 33 weeks and 35 to 37 weeks postmenstrual age (PMA). The semi-automated Retinal Image multiScale Analysis system was used to measure parameters for all arteries and veins: integrated curvature, diameter, and tortuosity index. A reference standard diagnosis (plus vs not plus) was defined for each eye by consensus of 5 experts at 35 to 37 weeks PMA. Weekly rate of change in parameters was compared in eyes with plus vs not plus disease. Receiver operating characteristic area under the curve (AUC) was calculated for plus disease detection based on 1) weekly rates of parameter change between 31 to 33 weeks and 35 to 37 weeks PMA and 2) parameter values at 35 to 37 weeks only.RESULTS: Weekly rates of change in all venous parameters were significantly different in eyes with plus vs not plus disease, particularly for tortuosity index (P < .0004) and diameter (P = .018). Using weekly rate of change, AUC for plus disease detection was highest for venous tortuosity index (0.819) and venous diameter (0.712). Using the 35 to 37-week PMA image only, AUC was highest for venous integrated curvature (0.952) and diameter (0.789).CONCLUSION: Rate of change in venous, but not arterial, parameters is correlated with plus disease development in this data set. This did not appear to contribute information beyond analysis of an image at 35 to 37 weeks PMA only. (Am J Ophthalmol 2010;150:468-475. (C) 2010 by Elsevier Inc. All rights reserved.)

PURPOSETo report an infant with inflicted neurotrauma who exhibited bilateral circumferential macular folds.METHODSBedside ophthalmic examination and fundus photography using RetCam-II (Clarity Medical Systems, Pleasanton, CA).RESULTSBoth pupils were miotic and nonreactive. External and anterior segments showed no abnormality. The fundus showed bilateral diffuse multilaminar retinal, subhyaloid, and vitreous hemorrhages. Distinctive macular folds were noted bilaterally.CONCLUSIONCircumferential macular folds are most commonly found in abused infants, although it has been suggested that they may be associated with Terson syndrome and severe crush injury.

Telemedicine has potential to improve quality and delivery of medical care, particularly in image-oriented specialties where decisions are based on appearance of morphological features during examination. In the ophthalmology domain, nearly all published telemedicine studies have measured accuracy against a gold standard of ophthalmoscopic examination. The purposes of this study are to examine difficulties in defining an absolute gold standard and to compare diagnostic speed in a representative disease, retinopathy of prematurity. We compare results from ophthalmoscopic and telemedicine examinations by the same physicians. In 180 (86.5%) of 208 eyes, the two examinations produced the same diagnosis. In some discrepancies, there was rationale suggesting that telemedicine may have provided a more accurate diagnosis than ophthalmoscopic examination. The quantity and nature of these disagreements has important implications for evaluation of telemedicine systems in image-based specialties, and for the definition of gold standards in future studies.

PURPOSE To review findings from the authors' published studies involving telemedicine and image analysis for retinopathy of prematurity (ROP) diagnosis.METHODS Twenty-two ROP experts interpreted a set of 34 wide-angle retinal images for presence of plus disease. For each image, a reference standard diagnosis was defined from expert consensus. A computer-based system was used to measure individual and linear combinations of image parameters for arteries and veins: integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) for plus disease diagnosis were determined for each expert. Sensitivity and specificity curves were calculated for the computer-based system by varying the diagnostic cutoffs for arterial IC and venous diameter. Individual vessels from the original 34 images were identified with particular diagnostic cutoffs, and combined into composite wide-angle images using graphics editing software.RESULTS For plus disease diagnosis, expert sensitivity ranged from 0.308-1.000, specificity from 0.571-1.000, and AUC from 0.784 to 1.000. Among computer system parameters, one linear combination had AUC 0.967, which was greater than that of 18 of 22 (81.8%) experts. Composite computer-generated images were produced using the arterial IC and venous diameter values associated with 75% under-diagnosis of plus disease (ie, 25% sensitivity cutoff), 50% under-diagnosis of plus disease (ie, 50% sensitivity cutoff), and 25% under-diagnosis of plus disease (ie, 75% sensitivity cutoff).CONCLUSIONS Computer-based image analysis has the potential to diagnose severe ROP with comparable or better accuracy than experts, and could provide added value to telemedicine systems. Future quantitative definitions of plus disease might improve diagnostic objectivity. (J AAPOS 2009;13:438-445)

Retinopathy of prematurity (ROP) is a vasoproliferative disorder affecting low birth weight infants. Although timely diagnosis and treatment can significantly reduce the risk of severe complications, ROP remains a leading cause of childhood blindness worldwide. Limitations of current disease management strategies include extensive travel and logistical coordination requirements for ophthalmologists and neonatologists, decreasing availability of adequately trained ophthalmologists at the point of care, variability in how retinal findings are diagnosed and documented, and a growing need for ROP care worldwide. Store-and-forward telemedicine is an emerging technology by which medical data are captured for subsequent interpretation by a remote expert. This has potential to improve accessibility, quality, and cost of ROP management. In this article, we summarize the current evaluation data on applications of telemedicine for ROP, particularly involving the diagnostic accuracy and reliability of remote image interpretation by experts. We also address challenges such as the cost-effectiveness of telemedicine, and highlight potential barriers to implementation of these systems. Understanding these principles is essential to determine future directions in research and development of telemedicine systems for ROP, as well as for other ophthalmic diseases.

PURPOSE: To compare the speed of retinopathy of prematurity (ROP) diagnosis using standard indirect ophthalmoscopy with that of telemedicine.DESIGN: Prospective, comparative study.METHODS: Three study examiners (2 pediatric retinal specialists [R.V.P.C., T.C.L.] and I pediatric ophthalmologist [M.F.C.]) conducted ROP diagnosis via standard indirect ophthalmoscopy and telemedicine. Each examiner performed: 1) standard ophthalmoscopy on 72 to 150 consecutive infants at his respective institution and 2) telemedical diagnosis on 125 consecutive deidentified retinal image sets from infants from an at,risk population. Time for ophthalmoscopic diagnosis was measured in 2 ways: 1) time spent by the examiner at the infant's bedside and 2) mean total time commitment per infant. Time for telemedicine diagnosis was recorded by computer time stamps in the web,based system. For each examiner, nonparametric statistical analysis (Mann-Whitney U test) was used to compare the distribution of times for examination by ophthalmoscopy vs telemedicine.RESULTS: Mean (+/- standard deviation [SD]) times for ophthalmoscopic diagnosis ranged from 4.17 (+/- 1.34) minutes to 6.63 (+/- 2.28) minutes per infant. Mean (+/- SD) times for telemedicine diagnosis ranged from 1.02 (+/- 0.27) minutes to 1.75 (+/- 0.80) minutes per infant. Telemedicine was significantly faster than ophthalmoscopy (P < .0001). The total time commitment by ophthalmologists performing bedside ophthalmoscopy for ROP diagnosis, including travel and communication with families and hospital staff, was 10.08 (+/- 2.53) minutes to 14-42 (+/- 2.64) minutes per infant.CONCLUSIONS: The ophthalmologist time requirement for telemedical ROP diagnosis is significantly less than that for ophthalmoscopic diagnosis. Additional time requirements associated with bedside ROP diagnosis in, creased this disparity. Telemedicine has potential to alleviate the time commitment for ophthalmologists who manage ROP. (Am J Ophthalmol 2009;148:136-142. (C) 2009 by Elsevier Inc. All rights reserved.)

Purpose: We studied clinical phenotyping and TEAD1 expression in mice and humans to gain a better understanding of the primary origin in the pathogenesis of circumpapillary dysgenesis of the pigment epithelium.Design: Observational case series and experimental study.Participants: Three female patients from an affected family were included for phenotypic study. Mice and human tissues were used for biochemistry and immunohistochemistry studies.Methods: We performed genetic analyses and longitudinal clinical, imaging, and electrophysiologic studies in a 3-generation family. Western blotting and immunohistochemistry were used to detect TEAD1 expression in mice and human retinal tissues.Main Outcome Measures: Autofluorescence and optical coherence tomography (OCT) imaging were compared and reviewed from 3 patients. TEAD1 expression was compared in different tissues from mice and human samples.Results: A point mutation at T1261 in TEAD1 was detected in the mother. Autofluorescence and OCT imaging studies revealed choroid is involved earlier than retinal pigment epithelium (RPE). From immunoblot analysis, we discovered that TEAD1 and its cofactors YAP65 and FOXA2 are expressed in the choroid. Immunohistochemical analysis on frozen sections of mouse retina supports immunoblot results.Conclusions: The primary cellular origin of circumpapillary dysgenesis of the pigment epithelium is within the choroid instead of the pigment epithelium. The loss of the RPE and photoreceptors in later stages of the disease is a secondary consequence of choroidal degeneration. Studies of the downstream targets of TEAD1 in choroidal cells will provide promising new research opportunities for the development of treatments for choroidal diseases.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:971-980 (C) 2009 by the American Academy of Ophthalmology.

Telemedicine is an emerging technology with potential to improve care for retinopathy of prematurity (ROP). This study evaluates parental perceptions about digital imaging and telemedicine for ROP care.

PURPOSE To demonstrate a methodology for generating composite wide-angle images of plus disease in retinopathy of prematurity (ROP), using quantitative analysis of expert opinions. METHODS Thirty-four wide-angle retinal images were independently interpreted by 22 ROP experts as "plus" or "not plus." All images were processed by the computer-based Retinal Image multiScale Analysis (RISA) system to calculate two parameters: arterial integrated curvature (AIC) and venous diameter (VD). Using a reference standard defined by expert consensus, sensitivity and specificity curves were calculated by varying the diagnostic cutoffs for AIC and VD. From these curves, individual vessels from multiple images were identified with particular diagnostic cutoffs, and were combined into composite wide-angle images using graphics-editing software. RESULTS The values associated with 75% underdiagnosis of true plus disease (i.e., 25% sensitivity cutoff) were AIC 0.061 and VD 4.272, the values associated with 50% underdiagnosis of true plus disease (i.e., a 50% sensitivity cutoff) were AIC 0.049 and VD 4.088, and the values associated with 25% underdiagnosis of true plus disease (i.e., 75% sensitivity cutoff) were AIC 0.042 and VD 3.795. Composite wide-angle images were generated by identifying and combining individual vessels with these characteristics. CONCLUSIONS Computer-based image analysis permits quantification of retinal vascular features, and a spectrum of abnormalities is seen in ROP. Selection of appropriate vessels from multiple images can produce composite plus disease images corresponding to expert opinions. This method may be useful for educational purposes, and for development of future disease definitions based on objective, quantitative principles.