Table 4 Clinical approach to diagnosis of patients with negative ERGs.
Features in patient history | |
Ocular history | • CSNB patients have stationary, congenital visual impairment, and are associated with myopia. XLRS usually presents in childhood. Rapidly progressive visual loss aged 4–8 can be seen in juvenile Batten disease. Acquired conditions usually have much later onset of symptoms |
• More acute/subacute onset of symptoms in adult (e.g. photopsia, night blindness) could reflect autoimmune (including paraneoplastic) disorders or inflammatory/vascular disorders. Some genetic conditions can present in adulthood | |
• History of IOFB or penetrating injury may point towards siderosis | |
General medical history | • Specific neurological/neuromuscular/metabolic systemic diagnoses |
• Medication history to include quinine, vigabatrin (and methanol) | |
• Known diagnosis or symptoms suggestive of cancer or melanoma | |
• Dietary insufficiency or intestinal or liver disease that could result in VAD | |
Family history | • Male with X-linked pedigree suggests X-linked genes (RS1, NYX, CACNA1F) |
• Other generations not affected in autosomal recessive diseases (unless pseudodominance/consanguinity) | |
• Dominant family history in CRX-related disease | |
Features on non-invasive retinal imaging | |
Colour fundus imaging, OCT, AF | • Myopic changes in CSNB |
• Schisis in XLRS (sometimes macular outer retinal atrophy in adult) | |
• Bull’s eye maculopathy and progressive degeneration in CLN3-associated Batten disease | |
• Range of changes possible in CRX-related retinopathy, but symmetric | |
• Sheen in Oguchi disease; small white dots in fundus albipunctatus and in VAD | |
• Outer retinal abnormalities, non-specific thinning, pigmentary changes possible in autoimmune and inflammatory retinopathies, often asymmetric | |
• Typical pale depigmented lesions in Birdshot chorioretinopathy. Inflammatory conditions may have cystoid macular oedema | |
• Inner retinal OCT hyper-reflectivity and swelling in CRAO followed by loss of inner retinal layers over weeks months. Widespread haemorrhages in CRVO | |
• Evidence of trauma or IOFB in siderosis | |
FFA, ICG | • FFA can delineate ischaemia/leakage in retinovascular/inflammatory disease |
• ICG can help in choroidal diseases; hypofluorescent lesions in Birdshot | |
Features relating to ERGs | |
Are the abnormalities bilateral and symmetric? | • Genetic diseases, systemic drug toxicities, and Vitamin A deficiency should give symmetric abnormalities |
• Ocular siderosis and central retinovascular occlusions are usually unilateral | |
• Paraneoplastic, inflammatory, autoimmune conditions may be unilateral or bilateral, and can be asymmetric | |
Is the DA 10 a-wave normal-sized or subnormal? | • Normal-sized in CSNB, XLRS |
• Normal-sized in CRAO and CRVO and certain drug toxicities | |
• May be normal-sized in MAR, but can be variable in other inflammatory and autoimmune retinopathies (including CAR) | |
• Can be normal or subnormal in CRX-related disease | |
• A-wave usually subnormal in fundus albipunctatus, Oguchi disease, Batten disease and other diseases affecting photoreceptors | |
• A-wave subnormal in VAD | |
What is the shape of the LA responses? | • Shape may reflect selective ON pathway dysfunction (cCSNB, MAR) or combined ON and OFF dysfunction (other conditions)—see Figs. 2 and 3 |
• LA response may be normal when cone system function normal (and DA responses reflect intact cone function) | |
