Colour vision deficiency and inherited retinal disease: SAQ

This two-part stem sets the two ends of the spectrum against each other, the benign and the common colour vision deficiency of the schoolboy and the severe and the treatable congenital retinal dystrophy of the infant, and the task is to outline the assessment and the management of the colour defect, and then to discuss the diagnostic pathway and the treatment of the congenital retinal dystrophy, contrasting the two with the precision the boards reward. [6][1]

Question 1 (10 marks)

Outline the assessment and the management of the colour vision deficiency in this six-year-old boy. [6]

A full-mark answer covers the interpretation of the Ishihara test, the distinction of the congenital from the acquired defect, the inheritance and the counselling, and the management. [6]

The Ishihara test and its interpretation (3 marks). The boy reads four of the fourteen screening plates, which is below the threshold of twelve or more that defines the normal, and the pattern of the misreading indicates the red-green defect, with the deuteranomaly as the commonest form. The Ishihara is the excellent screen for the red-green defect, and it is the poor test for the blue-yellow tritan defect, which the Hardy-Rand-Rittler plates and the Farnsworth tests detect better and the anomaloscope measures as the gold standard. [6]

The distinction of the congenital from the acquired (2 marks). The normal acuity, the full fields, the healthy fundus and the stable course confirm the congenital defect, while the acquired defect would be the new and the progressive change pointing to the optic neuropathy, the macular disease or the drug toxicity, with the tritan blue-yellow pattern as the common acquired form. The absence of the progression and the healthy fundus settle the question in favour of the congenital form. [6]

The inheritance (2 marks). The red-green colour deficiency is the X-linked recessive trait of the OPN1LW and the OPN1MW opsin genes on the X chromosome, and it affects roughly one in twelve males and well under one percent of the females. The mother is the carrier and the son is the affected male, and the family history of the colour-blind maternal relatives supports the inheritance. [6][8]

The management (3 marks). The colour vision deficiency has no treatment and it needs none, because it is stable and it carries no threat to the sight. The management is the honest explanation, the reassurance that the acuity and the field are normal, and the vocational advice that guides the boy away from the careers that demand the perfect colour discrimination, such as the electrical work, the aviation and the railway signalling. The tinted lenses may aid the discrimination but they do not correct the defect. [6]

Question 2 (10 marks)

Discuss the diagnostic pathway and the treatment of the infant with the nystagmus, the poor fixation and the near-absent electroretinography, contrasting the condition with the colour vision deficiency and addressing the gene therapy. [1]

A full-mark answer reproduces the differential, the electrophysiology, the genetic testing and the gene therapy. [3]

The differential and the urgency (2 marks). The roving eye movements, the nystagmus, the poor fixation and the near-absent electroretinography in the infant point to the congenital retinal dystrophy, and the leading diagnosis is the Leber congenital amaurosis, with the achromatopsia, the congenital stationary night blindness and the cortical visual impairment in the differential. The contrast with the colour vision deficiency is absolute, because the colour defect carries the normal acuity and the full field while the congenital retinal dystrophy carries the severe vision loss. [1]

The electroretinography and the imaging (3 marks). The full-field electroretinography measures the rod and the cone response, and the near-absent rod and cone response confirms the severe pan-retinal dystrophy of the Leber congenital amaurosis. The optical coherence tomography shows the viability of the retinal cells, which the gene therapy demands, and the fundus autofluorescence maps the retained retina. The imaging and the electrophysiology together classify the dystrophy and assess the eligibility for the gene therapy. [1][8]

The molecular genetic testing (2 marks). The next-generation sequencing panel of the inherited retinal disease genes, now covering over a hundred and seventy genes, identifies the pathogenic variant, and the biallelic RPE65 mutation is the one that opens the gene therapy. The genetic testing is the gateway to the treatment, and the candidate who holds the RPE65 link earns the marks. [9][11]

The gene therapy (3 marks). The voretigene neparvovec is the approved gene therapy for the biallelic RPE65 mutation with the viable retinal cells, delivered as the single subretinal injection of the adeno-associated virus vector carrying the normal RPE65 gene into each eye. The Russell phase three trial showed the improvement of the functional vision on the multi-luminance mobility test, with the durable gain at the one-year and the longer follow-up of Maguire, and it secured the first approval of a gene therapy for an inherited disease. The treatment is reserved for the RPE65 form, and it is not a cure, because it improves the functional vision rather than the full restoration of the sight. [3][4][11]