Incidence and Early Course of Retinopathy of Prematurity.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new. insight into the development of ROP.

OCULAR INVOLVEMENT IN HEMOPHAGOCYTIC SYNDROME: A NOVEL FUNDUSCOPIC MANIFESTATION AND REVIEW OF THE LITERATURE.

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.

Plus disease in retinopathy of prematurity: quantitative analysis of vascular change.

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.

Bilateral circumferential macular folds in inflicted childhood neurotrauma.

PURPOSE: To report an infant with inflicted neurotrauma who exhibited bilateral circumferential macular folds. METHODS: Bedside ophthalmic examination and fundus photography using RetCam-II (Clarity Medical Systems, Pleasanton, CA). RESULTS: Both 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. CONCLUSION: Circumferential 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.

Telemedical diagnosis of retinopathy of prematurity: accuracy of expert versus non-expert graders.

BACKGROUND/AIMS: To assess accuracy of telemedical retinopathy of prematurity (ROP) diagnosis by trained non-expert graders compared with expert graders. METHODS: Eye examinations (n=248) from 67 consecutive infants were captured using wide-angle retinal photography (RetCam-II, Clarity Medical Systems, Pleasanton, California, USA). Non-expert graders attended two 1-h training sessions on image-based ROP diagnosis. Using a web-based telemedicine system, 14 non-expert and three expert graders provided a diagnosis for each eye: no ROP, mild ROP, type 2 pre-threshold ROP or treatment-requiring ROP. All diagnoses were compared with a reference standard of dilated indirect ophthalmoscopy by an experienced paediatric ophthalmologist. RESULTS: For detection of type 2 or worse ROP, the mean (range) sensitivities and specificities were 0.95 (0.94-0.97) and 0.93 (0.91-0.96) for experts, 0.87 (0.71-0.97) and 0.73 (0.39-0.95) for resident non-experts, and 0.73 (0.41-0.88) and 0.91 (0.84-0.96) for student non-experts, respectively. For detection of treatment-requiring ROP, the mean (range) sensitivities and specificities were 1.00 (1.00-1.00) and 0.93 (0.88-0.96) for experts, 0.88 (0.50-1.00) and 0.84 (0.71-0.98) for resident non-experts, and 0.82 (0.42-1.00) and 0.92 (0.83-0.97) for student non-experts, respectively. CONCLUSIONS: Mean sensitivity and specificity of trained non-experts were lower than that of experts, although several non-experts had high accuracy. Development of methods for training non-expert graders may help support telemedical ROP evaluation.

Parental perceptions toward digital imaging and telemedicine for retinopathy of prematurity management.

BACKGROUND: 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. METHODS: During a 1-year period, one parent of each infant who underwent wide-field retinal imaging for ROP was given a questionnaire designed to evaluate parental perceptions using a 5-point Likert-type scale. Five items assessed perceptions toward digital retinal imaging, and ten items assessed attitudes toward telemedicine. Construct validity of the questionnaire was examined using factor analysis. Responses were summarized using descriptive and correlational statistics. RESULTS: Forty-two parents participated. Factor analysis extracted two factors explaining 79% of the total variance in digital retinal imaging items (Cronbach's alpha = 0.843), and three factors explaining 63% of the total variance in telemedicine items (Cronbach's alpha = 0.631). Among digital imaging items, the highest mean (+/-SD) score was for "digital pictures of my child's retinopathy should be included in the permanent medical record" (4.4 +/- 0.6), and the lowest was for "digital cameras and computers are reliable" (3.8 +/- 0.8). Among telemedicine items, the highest mean (+/-SD) score was for "technology will improve the quality of medical care for my child" (4.3 +/- 0.6), and the lowest was for "technology will make it harder for a patient and doctor to establish a good relationship" (2.6 +/- 1.1). CONCLUSIONS: Parents reported positive perceptions about telemedical ROP diagnosis, but expressed some preference for face-to-face care. Telemedicine has potential to alter the nature of the patient-physician relationship.

Image analysis for retinopathy of prematurity diagnosis.

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.

Telemedicine for retinopathy of prematurity diagnosis: evaluation and challenges.

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.

Cellular and molecular origin of circumpapillary dysgenesis of the pigment epithelium.

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.

Speed of telemedicine vs ophthalmoscopy for retinopathy of prematurity diagnosis.

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 1 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 increased this disparity. Telemedicine has potential to alleviate the time commitment for ophthalmologists who manage ROP.

uPA is upregulated by high dose celecoxib in women at increased risk of developing breast cancer.

BACKGROUND: While increased urokinase-type plasminogen activator (uPA) expression in breast cancer tissue is directly associated with poor prognosis, recent evidence suggests that uPA overexpression may suppress tumor growth and prolong survival. Celecoxib has been shown to have antiangiogenic and antiproliferative properties. We sought to determine if uPA, PA inhibitor (PAI)-1 and prostaglandin (PG)E2 expression in nipple aspirate fluid (NAF) and uPA and PGE2 expression in plasma were altered by celecoxib dose and concentration in women at increased breast cancer risk. METHODS: NAF and plasma samples were collected in women at increased breast cancer risk before and 2 weeks after taking celecoxib 200 or 400 mg twice daily (bid). uPA, PAI-1 and PGE2 were measured before and after intervention. RESULTS: Celecoxib concentrations trended higher in women taking 400 mg (median 1025.0 ng/mL) compared to 200 mg bid (median 227.3 ng/mL), and in post- (534.6 ng/mL) compared to premenopausal (227.3 ng/mL) women. In postmenopausal women treated with the higher (400 mg bid) celecoxib dose, uPA concentrations increased, while PAI-1 and PGE2 decreased. In women taking the higher dose, both PAI-1 (r = -.97, p = .0048) and PGE2 (r = -.69, p = .019) in NAF and uPA in plasma (r = .45, p = .023) were correlated with celecoxib concentrations. CONCLUSION: Celecoxib concentrations after treatment correlate inversely with the change in PAI-1 and PGE2 in the breast and directly with the change in uPA in the circulation. uPA upregulation, in concert with PAI-1 and PGE2 downregulation, may have a cancer preventive effect.

Retinopathy of prematurity management using single-image vs multiple-image telemedicine examinations.

PURPOSE: To compare performance of single-image vs multiple-image telemedicine examinations for retinopathy of prematurity (ROP) diagnosis. DESIGN: Prospective comparative study. METHODS: A total of 248 eyes from 67 consecutive infants underwent wide-angle retinal imaging by a trained neonatal nurse at 31 to 33 weeks and/or 35 to 37 weeks postmenstrual age (PMA) at a single academic institution. Data were uploaded to a web-based telemedicine system and interpreted by three masked retinal specialists. Diagnoses were provided based on single images, and subsequently on multiple images, from both eyes of each infant. Findings were compared to a reference standard of indirect ophthalmoscopy by a pediatric ophthalmologist. Primary outcome measures were recommended follow-up interval, presence of plus disease, presence of type-2 or worse ROP, and presence of visible peripheral ROP. RESULTS: Among the three graders, mean sensitivity/specificity for detection of infants requiring follow-up in less than one week were 0.85/0.93 by single-image examination and 0.91/0.88 by multiple-image examination at 35 to 37 weeks PMA. Mean sensitivity/specificity for detection of infants with type-2 or worse ROP were 0.82/0.95 by single-image examination and 1.00/0.91 by multiple-image examination at 35 to 37 weeks PMA. Mean sensitivity/specificity for detection of plus disease were 1.00/0.86 by single-image examination and 1.00/0.87 by multiple-image examination at 35 to 37 weeks PMA. There were no statistically-significant intragrader differences between accuracy of single-image and multiple-image telemedicine examinations for detection of plus disease. CONCLUSIONS: Single-image and multiple-image telemedicine examinations perform comparably for determination of recommended follow-up interval and detection of plus disease. This may have implications for development of screening protocols, particularly in areas with limited access to ophthalmic care.

Telemedical diagnosis of retinopathy of prematurity intraphysician agreement between ophthalmoscopic examination and image-based interpretation.

OBJECTIVE: To evaluate the intraphysician agreement between ophthalmoscopic examination and image-based telemedical interpretation for retinopathy of prematurity (ROP) diagnosis, when performed by the same expert physician grader. DESIGN: Prospective, nonrandomized, comparative study. PARTICIPANTS: Sixty-seven consecutive premature infants who underwent ROP examination at a major university medical center whose parents consented for participation. METHODS: Infants underwent standard dilated ophthalmoscopy by one of two pediatric ophthalmologists, followed by retinal imaging with a commercially available wide-angle fundus camera by a trained neonatal nurse. Study examinations were performed at 31 to 33 weeks postmenstrual age (PMA) and/or 35 to 37 weeks PMA. Images were uploaded to a Web-based telemedicine system developed by the authors. After a 4- to 12-month period, telemedical interpretations were performed in which each physician graded images from infants upon whom he had initially performed ophthalmoscopic examinations. Diagnoses were classified using an ordinal scale: no ROP, mild ROP, type 2 prethreshold ROP, and treatment-requiring ROP. MAIN OUTCOME MEASURES: Absolute intraphysician agreement and kappa statistic between ophthalmoscopic examination and telemedical interpretation were calculated by eye. All intraphysician discrepancies were reviewed, and underlying causes were classified by eye as no ROP identified by ophthalmoscopic examination, no ROP identified by telemedical interpretation, discrepancy about presence of zone 1 ROP, discrepancy about presence of plus disease, or other discrepancy in classification of ROP stage. RESULTS: Absolute intraphysician agreement between ophthalmoscopic examination and telemedical interpretation was 86.3%. The kappa statistic for intraphysician agreement between examinations ranged from 0.657 (substantial agreement) for diagnosis of treatment-requiring ROP to 0.854 (near-perfect agreement) for diagnosis of mild or worse ROP. Among 206 eye examinations (103 infant examinations), there were 28 (13.6%) intraphysician discrepancies in diagnosis, 8 of which resulted from uncertainty about presence of zone 1 disease and 4 from uncertainty about presence of plus disease. CONCLUSIONS: Intraphysician agreement between ophthalmoscopic examination and telemedical interpretation for ROP was very high. Neither examination modality appeared to have a systematic tendency to overdiagnose or underdiagnose ROP. Diagnosis of zone 1 disease and plus disease were major sources of clinically significant discrepancies.

Plus disease in retinopathy of prematurity: development of composite images by quantification of expert opinion.

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.

Cost-utility analysis of telemedicine and ophthalmoscopy for retinopathy of prematurity management.

OBJECTIVE: To evaluate the cost-effectiveness of telemedicine and standard ophthalmoscopy for retinopathy of prematurity (ROP) management. METHODS: Models were developed to represent ROP examination and treatment using telemedicine and standard ophthalmoscopy. Cost-utility analysis was performed using decision analysis, evidence-based outcome data from published literature, and present value modeling. Visual outcome data were converted to patient preference-based time trade-off utility values based on published literature. Costs of disease management were determined based on 2006 Medicare reimbursements. Costs per quality-adjusted life year gained by telemedicine and ophthalmoscopy for ROP management were compared. One-way sensitivity analysis was performed on the following variables: discount rate (0%-7%), incidence of treatment-requiring ROP (1%-20%), sensitivity and specificity of ophthalmoscopic diagnosis (75%-100%), percentage of readable telemedicine images (75%-100%), and sensitivity and specificity of telemedicine diagnosis (75%-100%). RESULTS: For infants with birth weight less than 1500 g using a 3% discount rate for costs and outcomes, the costs per quality-adjusted life year gained were $3193 with telemedicine and $5617 with standard ophthalmoscopy. Sensitivity analysis resulted in ranges of costs per quality-adjusted life year from $1235 to $18,898 for telemedicine and from $2171 to $27,215 for ophthalmoscopy. CONCLUSIONS: Telemedicine is more cost-effective than standard ophthalmoscopy for ROP management. Both strategies are highly cost-effective compared with other health care interventions.

Celecoxib concentration predicts decrease in prostaglandin E2 concentrations in nipple aspirate fluid from high risk women.

BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib. METHODS: Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib. RESULTS: In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE2 levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE2 concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03). CONCLUSION: In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE2 production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE2 are of interest, in order to minimize the celecoxib dose required to have an effect.

Evaluation of a computer-based system for plus disease diagnosis in retinopathy of prematurity.

OBJECTIVE: To measure accuracy and reliability of the computer-based Retinal Image Multiscale Analysis (RISA) system compared with those of recognized retinopathy of prematurity (ROP) experts, for plus disease diagnosis. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Eleven recognized ROP experts and the RISA image analysis system interpreted a set of 20 wide-angle retinal photographs for presence of plus disease. METHODS: All experts used a secure Web site to review independently 20 images for presence of plus disease. Images were also analyzed by measuring individual computer-based system parameters (integrated curvature [IC], diameter, and tortuosity index) for arterioles and venules and by computing linear combinations and logical combinations of those parameters. Performance was compared with a reference standard, defined as the majority vote of experts. MAIN OUTCOME MEASURES: Diagnostic accuracy was measured by calculating sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) for plus disease diagnosis by each expert, and by each computer-based system parameter, compared with the reference standard. Diagnostic agreement was measured by calculating the mean kappa value of each expert compared with all other experts and the mean kappa value of each computer-based system parameter compared with all experts. RESULTS: Among the 11 experts, sensitivity ranged from 0.167 to 1.000, specificity ranged from 0.714 to 1.000, AUC ranged from 0.798 to 1.000, and mean kappa compared with all other experts ranged from 0.288 to 0.689. Among individual computer system parameters, arteriolar IC had the highest diagnostic accuracy, with sensitivity of 1.000; specificity, 0.846; and AUC, 0.962. Arteriolar IC had the highest diagnostic agreement with experts, with a mean kappa value of 0.578. CONCLUSIONS: A computer-based image analysis system has the potential to perform comparably to recognized ROP experts for plus disease diagnosis.

Telemedical retinopathy of prematurity diagnosis: accuracy, reliability, and image quality.

OBJECTIVE: To prospectively measure accuracy, reliability, and image quality of telemedical retinopathy of prematurity (ROP) diagnosis. METHODS: Two-hundred forty-eight eyes from 67 consecutive infants underwent wide-angle retinal imaging by a trained neonatal nurse at 31 to 33 weeks' and/or 35 to 37 weeks' postmenstrual age (PMA) using a standard protocol. Data were uploaded to a Web-based telemedicine system and interpreted by 3 expert retinal specialist graders who provided a diagnosis (no ROP, mild ROP, type 2 prethreshold ROP, treatment-requiring ROP) and an evaluation of image quality for each eye. Findings were compared with a reference standard of indirect ophthalmoscopy by an experienced pediatric ophthalmologist. RESULTS: At 35 to 37 weeks' PMA, sensitivity and specificity for diagnosis of mild or worse ROP were 0.908 and 1.000 for grader A, 0.971 and 1.000 for grader B, and 0.908 and 0.977 for grader C. Sensitivity and specificity for diagnosis of type 2 prethreshold or worse ROP were 1.000 and 0.943 for grader A, 1.000 and 0.930 for grader B, and 1.000 and 0.851 for grader C. At 35 to 37 weeks' PMA, weighted kappa for intergrader reliability was 0.791 to 0.889, and kappa for intragrader reliability for detection of type 2 prethreshold or worse ROP was 0.769 to 1.000. Image technical quality was rated as "adequate" or "possibly adequate" for diagnosis in 93.3% to 100% of eyes. CONCLUSION: A telemedicine system using nurse-captured retinal images has the potential to improve existing shortcomings of ROP management, particularly at later PMAs.