Genetic Testing of Inherited Retinal Disease in Australian Private Tertiary Ophthalmology Practice

Figures & data

Table 1 Demographics of All Patients and as Categorised by Age (Less Than 45 Years of Age, 45 Years or Older)

	Less Than 45 Years of Age	45 Years of Age or Older	Total	p-value
	(n=221)	(n=243)	(n=464)
Age, years median (IQR)	28 (20–36)	60 (53–69.5)	46 (28–60)
Gender, n (%)				<0.01
Male	128 (57.9%)	111 (45.7%)	239 (51.5%)
Female	93 (42.1%)	132 (54.3%)	225 (48.5%)
Duration of care, months, median (IQR)	1 (0–40)	13 (0–84)	5 (0–63.25)
Less than 12 months	135 (61.1%)	117 (48.1%)	252 (54.3%)	<0.01
12 months or more	86 (38.9%)	126 (51.9%)	212 (45.7%)
Genetic testing performed, n (%)	29 (13.1%)	15 (6.2%)	44 (9.5%)	0.01
Clinical Diagnosis, n (%)
Panretinal pigmentary retinopathies	137 (62%)	147 (60.5%)	284 (61.2%)	0.78
Retinitis pigmentosa/rod-cone dystrophy	99 (44.8%)	122 (50.2%)	221 (47.6%)
Cone-rod dystrophy	11 (5.0%)	9 (3.7%)	20 (4.3%)
Cone dystrophy	9 (4.1%)	11 (4.5%)	20 (4.3%)
Other Panretinal pigmentary retinopathies†	18 (8.1%)	5 (2.3%)	23 (5.0%)
Macular dystrophies	53 (24%)	84 (34.6%)	137 (29.5%)	<0.01
Macular atrophy/dystrophy with flecks	26 (11.8%)	30 (12.3%)	56 (12.1%)
Macular atrophy/dystrophy without flecks	20 (9%)	25 (10.3%)	45 (9.7%)
Other macular dystrophies ‡	7 (3.2%)	29 (11.9%)	36 (7.8%)
Stationary diseases	19 (8.6%)	4 (1.6%)	23 (5%)	<0.01
Congenital stationary night blindness	13 (5.9%)	1 (0.4%)	14 (3%)
Achromatopsia/dyschromatopsia	6 (2.7%)	3 (1.2%)	9 (1.9%)
Hereditary vitreoretinopathies	9 (4.1%)	5 (2.1%)	14 (3%)	0.28
Familial exudative vitreoretinopathy	7 (3.2%)	3 (1.2%)	10 (2.2%)
X-linked retinoschisis	2 (0.9%)	2 (0.8%)	4 (0.9%)
Other ¥	3 (1.2%)	3 (1.2%)	6 (1.3%)

Notes: †Other Panretinal pigmentary retinopathies include: Bietti’s crystalline corneoretinal dystrophy (n=1), choroideremia (n=5), Leber’s congenital amaurosis (n=7), Retinitis punctata albescens (n=3), S-cone/Goldman favre (n=4), gyrate atrophy (n=2), and “bilateral retinal dystrophy” as the documented diagnosis on the patient’s clinical records (n=1). ‡ Other macular dystrophies include Best’s vitelliform macular dystrophy (n=17), benign concentric annular macular dystrophy (n=5), butterfly-shaped pattern dystrophy (n=7), central areolar choroidal dystrophy (n=1), and bull’s eye maculopathy (n=5), and “macular dystrophy” as the documented diagnosis on the patient’s clinical records (n=1). ¥ Other clinical diagnoses include Wagner’s vitreoretinopathy (n=2), abetalipoproteinaemia (n=1), late-onset retinal degeneration (n=1), Batten disease with retinal involvement (n=1), and mucopolysaccharidosis II with retinal involvement (n=1).

Abbreviation: IQR; interquartile range.

Figure 1 Suspected mode of inheritance of inherited retinal disease, based upon genetic test results, family history of inherited retinal disease, or clinicians’ suspected mode of inheritance (as documented). Data presented as n, (%).

Figure 2 Documented reasons for absence of genetic test results, n (%). Awaiting geneticist and test results indicate patient has been referred for genetic testing, however, has not been seen or has not received results yet. “Not further specified” indicates that counselling regarding genetic testing was not documented on patients’ clinical records. Results presented as n, (%).

Table 2 Univariate and Multivariate Logistic Regression Assessing Predictors of Having Genetic Testing Results Among Patients

	Univariate Analysis		Multivariate Analysis
	OR (95% CI)	p-value	OR (95% CI)	p-value
Gender
Male	Ref		-	-
Female	0.79 (0.422–1.477)	0.46
Age
45 or over	Ref		Ref
Less than 45	2.30 (1.196–4.408)	0.01	2.95 (1.502–5.807)	<0.01
Duration of care
Less than 12 months	Ref		Ref
12 months or over	4.62 (2.225–9.603)	<0.01	5.48 (2.598–11.569)	<0.01

Table 3 Frequency of Genes Identified During Genetic Testing

Causative Genes Identified	Frequency Identified in Testing^†	% of Cohort (n=44)	Pathogenic (P), Likely Pathogenic (LP), Variant of Unknown Significance (VUS)^‡
ABCA4	6	13.6%	P: 100%
BEST1	3	6.8%	P: 50%; LP: 50%
USH2A	3	6.8%	VUS: 33%; LP: 66%
CRB1	2	4.5%	P: 50%; LP: 50%
MFRP	2	4.5%	LP: 100%
RHO	2	4.5%	P: 100%
BBS1	1	2.2%	P: 100%
BBS9	1	2.2%	P: 100%
CHM	1	2.2%	LP: 100%
CNGA3	1	2.2%	P: 100%
CRX	1	2.2%	LP: 100%
CSPP1	1	2.2%	P: 100%
EYS	1	2.2%	P: 100%
IFT2	1	2.2%	P: 100%
INPP5E	1	2.2%	P: 100%
FSCN2	1	2.2%	P: 100%
MT-ND5	1	2.2%	P: 100%
MT-TL1	1	2.2%	LP: 100%
NMNAT1	1	2.2%	LP: 100%
PEX7	1	2.2%	LP: 100%
PRPF8	1	2.2%	P: 100%
PRPS1	1	2.2%	P: 100%
RGR	1	2.2%	VUS: 100%
RP1	1	2.2%	LP: 100%
RP1L1	1	2.2%	P: 100%
RPGR	1	2.2%	P: 100%
SPATA7	1	2.2%	VUS: 100%
Disease-causing variant not identified	15	34.1%	N/A

Notes: ^†Pathogenicity was determined based on the genetic testing report obtained from the testing laboratory and/or geneticist or genetic counsellor and not by the respective clinician. ^‡ Some patients had multiple genes identified.