A proposal for an updated staging system for LCHADD retinopathy

Figures & data

Figure 1. First row; fundus images representing from stage 1 to 4. Second row representing fundus autofluorescence start from speckle hypoautofluorescence mostly within vascular arcades in stage 2A progressing to nearly total dense hypoautofluorescence towards periphery in stage 4 (red arrow) third row demonstrates cross-sectional OCT scan of central macular area comparing each stages, severe attenuation of choroid was observed by OCT in stage 3B.(yellow arrow) fourth and fifth rows showing scotopic ERG and photopic ERG response respectively, amplitude of b wave gradually decline in more advance stages.

Table 1. Clinical staging based on multimodality ophthalmological findings of patients with LCHADD chorioretinopathy.

Stage		Fundus		FfERG	Wide field FAF	OCT
		Posterior pole	Periphery			Retinal findings	Choroidal findings
1		normal		normal	normal	normal	normal
2	A	pigmentary deposition in the macular area		Normal	speckled hypo/hyperautofluorescence mostly within posterior pole and vascular arcades	normal to thickening of RPE-Bruch complex in macular, mild attenuation of EZ/RPE can be observed	normal
	B		more prominent pigmentary deposition spreading beyond the vascular arcades into the midperiphery	mildly to moderately decreased ffERG	speckled hypoautofluorescence beyond vascular arcades to the midperiphery	normal to thickening of RPE-Bruch complex in central fovea, mild attenuation of EZ/RPE can be observed	normal
3	A	partial chorioretinal atrophy, relative sparing of the central macula	pigmentary deposition beyond arcades and to periphery	mild to moderately decreased ffERG	Progressive enlargement of hypo autofluorescence from RPE loss (usually multiple well-demarcated nummular lesions) in macular area out towards the mid-periphery, with a meshwork of residual RPE hyperautofluorescence sparing	Progressive outer retina (EZ, RPE-Bruch membrane, ONL) attenuation, outer retinal tubulation	choroidal thickness normal or mild thinning
	B			moderate to severely decreased ffERG	enlargement areas of hypoautofluorescence toward mid-periphery with a meshwork of residual RPE hyperautofluorescence sparing	progressive outer retinal atrophy, outer retinal tubulation	progressive choroidal atrophy sparing central fovea (abrupt transition zones)
4		extensive atrophy of the posterior pole, totally loss central island in some cases, posterior staphyloma	pigmentary changes and progressive atrophy toward periphery	moderate to severely decreased ffERG to non-recordable	enlargement area of hypoautofluorescence with some degree of intact peripheral retina	extensive outer retinal atrophy, outer retinal tubulation	extensive choroidal atrophy sparing central fovea in most cases

*concurrent ocular findings which can be observed at Stage 2 and higher; CNV: choroidal neovascularization, ERM: epiretinal membrane, CME: cystoid macular edema.

LCHADD: long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency, ffERG: full-field electroretinography, FAF: fundus autofluorescence, OCT: optical coherence tomography, RPE: retinal pigment epithelium, EZ: ellipsoid zone, ONL: outer nuclear layer.

Table 2. A comparison of patient staging between the two systems of grading.

Case	Age	Side	VA (logMAR)	Tyni staging	New staging	Concurrent findings	Case	Age	Side	VA (logMAR)	Tyni staging	New staging	Concurrent findings
1	2	OD	NA	1	1		21	16	OD	0.50	4	4	ERM, CME
		OS	NA	1	1				OS	0.60	4	4	ERM, CME
2	3	OD	NA	2	2A		22	16	OD	−0.10	2	2A
		OS	NA	2	2A				OS	−0.22	2	2A
3	3	OD	NA	3	3A		23	17	OD	−0.10	1	1
		OS	NA	3	3A				OS	0.00	1	1
4	4	OD	NA	2	2A		24	17	OD	0.10	2	2B
		OS	NA	2	2A				OS	0.00	2	2B
5	7	OD	0.00	2	2A		25	17	OD	1.30	3	3B
		OS	0.00	2	2A				OS	1.00	3	3B
6	7	OD	−0.10	2	2A		26	17	OD	0.80	3	4	CNV
		OS	0.00	2	2A				OS	1.30	3	4	CNV
7	7	OD	0.00	1	1		27	18	OD	0.20	3	3A	CME
		OS	−0.10	1	1				OS	0.20	3	3A	CME
8	7	OD	0.30	3	3A		28	18	OD	0.10	2	2B	CNV
		OS	0.20	3	3A				OS	1.00	3	2B	CNV, ERM, CME
9	9	OD	0.50	3	3A	ERM, CME	29	18	OD	0.20	3	3B
		OS	0.40	3	3A	ERM, CME			OS	0.20	3	3B
10	9	OD	−0.10	1	1		30	18	OD	0.00	3	3A
		OS	−0.10	1	1				OS	−0.10	3	3A
11	10	OD	0.10	1	1		31	21	OD	1.00	4	4	CME
		OS	0.00	1	1				OS	0.70	4	4	CNV, CME
12	11	OD	−0.22	1	1		32	24	OD	0.00	3	3B	CME
		OS	−0.22	1	1				OS	0.70	3	3B	CNV, CME
13	11	OD	0.30	2	2A		33	24	OD	0.40	4	4	ERM, CME
		OS	0.00	2	2A				OS	0.20	4	4	ERM, CME
14	11	OD	−0.10	1	1		34	26	OD	−0.10	1	1
		OS	−0.22	1	1				OS	−0.10	1	1
15	12	OD	0.00	2	2B		35	27	OD	0.30	3	4	CNV, CME
		OS	0.00	2	2B				OS	2.10	4	4	CME
16	12	OD	0.10	2	2B		36	28	OD	0.20	3	3B	ERM, CME
		OS	0.30	2	2B				OS	0.10	3	3B	ERM, CME
17	13	OD	−0.10	2	2A		37	29	OD	1.60	4	4	CNV, ERM, CME
		OS	−0.10	2	2A				OS	0.20	4	4	ERM, CME
18	13	OD	−0.10	2	2A		38	30	OD	1.60	4	4	CME
		OS	−0.10	2	2A				OS	1.60	4	4	ERM, CME
19	15	OD	−0.10	1	1		39	31	OD	0.10	1	1
		OS	−0.10	1	1				OS	−0.10	1	1
20	15	OD	0.00	2	2A		40	36	OD	0.30	4	4
		OS	0.00	2	2A				OS	0.30	4	4	CNV

CNV: choroidal neovascularization, ERM: epiretinal membrane, CME: cystoid macular edema.