Sensitivity and specificity of the iVue iWellnessExam™ in detecting retinal and optic nerve disorders

Figures & data

Figure 1 Category 1 iWellness™ OU report for subject J749, with a normal healthy retina and ganglion cell complex.

Figure 2 Category 2 iWellnessExam™ report OS for subject J893.

Notes: Monocular report provides multiple high-resolution sections through the macula, in which both retinoschisis and a macular hole (scan 7) OS are identifiable. Despite the thickened central volume on the full retinal thickness map, the ganglion cell complex maintains its integrity and appears intact in the optical coherence tomography scans, with normal thickness shown on the ganglion cell complex map. See OU report, Figure 3.

Figure 3 Category 2 iWellness™ OU report for subject J893.

Notes: Retained symmetry of ganglion cell complex OD/OS, despite central retinal elevation with retinoschisis OS. In this case, the OU report helps to rule out the likelihood of optic nerve disease while simultaneously documenting retinal disease.

Figure 4 Category 3 iWellness™ OU report for subject J835.

Notes: 10 micron superior/inferior asymmetry OS, and 12 micron inferior asymmetry OD/OS. In this case, the OU report highlights the asymmetry both within the OS and between OD/OS. No retinal disease is apparent. See OS report, Figure 5.

Figure 5 Category 3 iWellness™ report OS for subject J835.

Notes: The high-resolution scans through the macula support the reviewer’s ability to assess the retina. In this case, the tilted scans depict a staphyloma, but the outer retina appears healthy, intact, and free of pathology. Hence, this subject “passed” the retinal screening but “failed” the optic nerve screening, with thinning of inferior ganglion cell complex OS (see OU report, Figure 4).

Figure 6 Category 4, iWellness™ OU report of subject J899.

Notes: OU report identifies an extremely thin ganglion cell complex OD and OS (more than 3 standard deviations below average), despite minimal intraocular or interocular asymmetry. Neurosensory retinal detachment OD is detected on both high-resolution scans displayed; pigment epithelial detachment is indicated in the horizontal scan OD, top-left, red arrow. Full retinal thickness maps show areas of retinal thickening superior nasal OD and OS (indicated by red arrows). These may also be serous detachments, which should be scanned in detail once identified on screening.

Table 1 Subject demographics by gender, ethnicity, and age

Demographics	Normal	Disease	Total
Gender
Female	94	53	147
Male	32	48	80
Ethnicity
African American	25	54	79
Caucasian	58	16	74
Asian	29	6	35
Hispanic	12	23	35
Other	2	2	4
Age
<35	78	5	83
36–50	22	12	34
51–65	22	39	61
66–80	3	33	36
≥81	1	12	13
Min	18	23
Max	82	95
Average	35.5	63.5
SD	15.1	14.2

Table 2 iWellnessExam sensitivity and specificity, on expert review

	Sensitivity			Specificity
	Any disease	Retinal disease	Optic nerve disease	Normal
Test (+)	97	64	45	1
Test (−)	4	3	5	125
	96.0%	95.5%	90.0%	99.2%

Table 3 iVue iWellnessExam receiver operator characteristic on expert review

	Any disease	Retinal disease	Optic nerve disease
False positive rate	0.008	0.008	0.008
True positive rate	0.960	0.955	0.900
Accuracy	0.978	0.979	0.966
Positive predictive value	99.0%	98.5%	97.8%
Negative predictive value	96.9%	97.7%	96.2%

Table 4 Pathologies encountered

Retinal diseases identified (subjects in category 2 or 4)
Diabetic retinopathy (DR)	14
Non-proliferative DR	11
Proliferative DR	3
Age-related macular degeneration (AMD)	16
Dry AMD	16
Wet AMD	0
Epiretinal membrane (ERM)	12
Macular hole	5
Clinically significant macular edema (CSME)	5
Clinically serous chorioretinopathy	3
Cystoid macular edema	2
Central retinal vein occlusion	4
Branch retinal vein occlusion	2
Hypertensive retinopathy	1
Myopic degeneration	8
Pigment epithelial detachment	2
Retinitis pigmentosa	2
Acute macular neuroretinopathy	1
Choroidal ectasia	1
Diffuse unilateral subacute neuroretinitis	1
Idiopathic vasculitis with hard exudates	1
Isolated, idiopathic cotton wool spot	1
Pericentral glial scar w/hemorrhage	1
Retinoschisis, macular	1
Toxoplasmosis	1
X-linked juvenile retinoschisis	1
	85
Optic nerve diseases identified (subjects in category 3 or 4)
Glaucoma	45
Open angle glaucoma	42
Narrow angle glaucoma	2
Mixed mechanism glaucoma	1
Non-glaucomatous neuroretinopathy	3
Diffuse unilateral subacute neuroretinitis	1
Optic disc drusen	1
	50

Table 5 Accuracy in the identification of both disease conditions, on expert review

	Retinal disease	Optic nerve disease	GCC abnormal 2° to retinal disease*
Under-detected	3	5	3
Over-reported	2	4	4

Abbreviation:

* GCC = Ganglion Cell Complex

Figure 7 Ganglion cell complex measurement reflects a subset of cells different to those used for the peripapillary retinal nerve fiber layer (RNFL) assessment.

Notes: Axons at the 12 o’clock, 6 o’clock, and nasal aspects of the optic nerve head are not represented in the ganglion cell complex measurement. However, the ganglion cell complex offers a magnified assessment of cells traveling in the papillomacular bundle. This particular region often fails to reach statistical significance on retinal nerve fiber layer (RNFL) assessment, owing to the thinner caliber of axons in this region. © Reprinted with permission OptoVue.

Figure 8 Category 2 subject (J728) with severe retinal distortion, interfering with retinal segmentation and ganglion cell complex thickness map and measurements.

Notes: Clinician inspects spectral domain optical coherence tomography scans directly in order to assess the retinal nerve fiber layer. Vertical slice (top-right) shows symmetric superior/inferior retinal nerve fiber layer thickness.

Figure 9 Category 2 subject (J911) with an epiretinal membrane and vitreomacular traction.

Notes: The traction creates an artificially thickened measurement of the ganglion cell complex, with distortions appreciated on the thickness map. Observation of the superior/inferior symmetry of the ganglion cell complex on the vertical scan (top right) and the integrity of the ganglion cell complex in the 7 (numbered) horizontal high resolution slices provides sufficient data to suggest a normal ganglion cell complex with overlying inner retinal distortion.