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OP9.4 | Posterior Segment Disorder Survey: Retinopathies, Detachment, Macular Disease, Dystrophy and Retinoblastoma — SDL Guide (Part 3)

Retinitis Pigmentosa and Retinoblastoma

Retinitis pigmentosa and retinoblastoma represent opposite ends of the clinical spectrum: one is a chronic, slowly progressive hereditary dystrophy; the other is an acute, life-threatening childhood malignancy requiring emergency referral.

Retinitis Pigmentosa (RP): a group of inherited retinal dystrophies characterised by progressive degeneration of photoreceptors — predominantly rods first, then cones. The inheritance pattern may be autosomal dominant (most common, mildest; PRPF31, RHO gene mutations), autosomal recessive (more severe), or X-linked recessive (severe, affects males primarily). More than 100 causative genes have been identified.

Clinical features follow the anatomical distribution of rods (periphery) and the temporal order of rod-then-cone death: night blindness (nyctalopia) is the earliest symptom (rod loss in the periphery); this is followed by progressive peripheral (tunnel) vision loss as the mid-periphery degenerates; and finally central vision loss when the macula is involved in advanced disease. On fundoscopy, the classic triad: bone-spicule pigmentation (clusters of black pigment in the mid-peripheral retina, shaped like the cells of cortical bone), arteriolar attenuation (markedly narrowed retinal arteries — reflecting the reduced metabolic demand of dying photoreceptors), and waxy disc pallor (optic atrophy from trans-synaptic degeneration). ERG is extinguished or markedly reduced — a characteristic and diagnostic finding. There is currently no curative treatment; low-vision aids, light-avoidance strategies, and genetic counselling are offered. Gene therapy trials are underway. RP can be part of systemic syndromes: Usher syndrome (RP + congenital deafness), Laurence-Moon-Bardet-Biedl syndrome, Refsum disease.

Retinoblastoma: the most common primary intraocular malignancy of childhood, arising from retinal progenitor cells with biallelic loss of the RB1 tumour suppressor gene (chromosome 13q14). Heritable form (40% of cases) has a germline mutation in one allele (inherited from an affected parent or a new germline mutation) and a second somatic hit in the other allele; heritable RB is often bilateral and multifocal. Sporadic form (60%) requires two independent somatic mutations; typically unilateral.

Presentation: most commonly in children under 5 years. The most common presenting sign is leukocoria — a white pupillary reflex or white spot in photographs, replacing the normal red reflex. Other presentations: strabismus (from macular involvement), proptosis (extraocular extension, advanced), or red painful eye (secondary glaucoma). Never reassure leukocoria — this is a medical emergency; delayed diagnosis allows extraocular extension (orbital, optic nerve to CNS) which dramatically worsens prognosis and survival.

Management depends on the extent: systemic chemotherapy (vincristine, carboplatin, etoposide — VCE chemoreduction) followed by focal consolidation (laser, cryotherapy, or plaque brachytherapy) for localised tumours; enucleation (removal of the eye) for advanced unilateral tumours where vision cannot be saved; external beam radiotherapy (last resort, causes orbital growth abnormalities and second malignancy risk in heritable cases). Survival exceeds 95% in high-resource settings when diagnosed early and confined to the globe. Genetic counselling and screening of siblings is mandatory in heritable cases.

Management Principles and Referral Pathways

Across the range of posterior segment disorders covered in this module — retinal detachment, hypertensive retinopathy, Eales disease, retinopathy of prematurity, age-related macular degeneration, central serous retinopathy, macular holes, retinitis pigmentosa, and retinoblastoma — management follows a unified set of clinical principles that reflect the urgency, reversibility, and specific treatment options for each condition. The primary care physician and non-specialist physician play a critical role in this framework: they are often the first clinician to encounter these presentations, and the speed and appropriateness of their referral decision can be the determining factor in whether the patient retains useful vision. Knowing which conditions constitute same-day emergencies, which require referral within days, and which can be managed electively is therefore a core competency for any clinician who examines the posterior segment, interprets fundoscopy findings, or manages patients with systemic diseases that have retinal manifestations.

Emergency referrals (same day/hours):
- Leukocoria in a child → retinoblastoma exclusion by an ophthalmologist (same day)
- Symptomatic retinal detachment with 'curtain' shadow → surgical ophthalmology (within hours for macula-on RRD)
- Hypertensive retinopathy grade IV → emergency BP management (ICU/HDU); ophthalmology to confirm papilloedema

Urgent referrals (within days):
- New photopsia/floaters without frank field defect → ophthalmology within 24 hours to examine for retinal tear before RRD develops
- Sudden central vision loss with metamorphopsia → ophthalmology within 48-72 hours (wet AMD with CNV responds better to earlier anti-VEGF)
- ROP screening due → ophthalmologist at specified gestational age intervals (delay is unacceptable in a premature infant)

Routine referrals:
- Dry AMD (drusen only, no CNV) → ophthalmology for grading and AREDS2 advice
- Retinitis pigmentosa → ophthalmology and genetic counselling
- Eales disease (inactive phase) → ophthalmology for surveillance

Key management tools:
- Laser photocoagulation: laser PRP for ischaemic Eales/ROP; sector laser for BRVO; laser retinopexy for retinal tears (before they detach); micropulse laser for chronic CSR
- Intravitreal anti-VEGF: wet AMD, CMO from vascular causes, ROP zone I disease
- Photodynamic therapy (PDT): used for classic CNV in wet AMD (historically) and half-dose PDT for chronic CSR
- Surgery (PPV/scleral buckling): rhegmatogenous and tractional RD; non-clearing vitreous haemorrhage in Eales/PDR
- Systemic chemotherapy + focal therapy: retinoblastoma
- Genetic counselling: mandatory for RP (hereditary) and heritable retinoblastoma (RB1 germline mutation)
- Systemic risk factor control: BP (hypertensive retinopathy), corticosteroid discontinuation (CSR), oxygen management in neonates (ROP prevention)

Self-Assessment

Apply your knowledge with these structured clinical reasoning questions.

Question 1. A patient with BP 230/140 mmHg is found on fundoscopy to have bilateral flame haemorrhages, macular star (hard exudates arranged radially around the macula), and bilateral blurred disc margins. What is the KWB grade of hypertensive retinopathy, and what is the immediate management?
Answer: This is KWB grade IV hypertensive retinopathy (grade III changes — haemorrhages, hard exudates, cotton-wool spots — plus papilloedema = grade IV). This is a hypertensive emergency (hypertensive encephalopathy). Immediate management: IV antihypertensive therapy (labetalol IV infusion, or sodium nitroprusside in an HDU setting) targeting approximately 25% reduction in mean arterial pressure in the first hour. Do not reduce BP too rapidly (risk of ischaemic stroke and watershed infarcts). Ophthalmology referral to confirm and document papilloedema.

Question 2. How does the mechanism of rhegmatogenous retinal detachment differ from tractional retinal detachment? Name one condition that is the commonest cause of each type.
Answer: Rhegmatogenous RD results from a break (tear or hole) in the retina allowing vitreous fluid to flow beneath and lift it off — the primary event is the retinal break. Commonest cause: myopia with posterior vitreous detachment (PVD) causing a horseshoe tear. Tractional RD results from fibrovascular membranes forming on the vitreoretinal interface and physically pulling the retina off the RPE — there is no break in the retina itself. Commonest cause: proliferative diabetic retinopathy (PDR).

Question 3. A 3-year-old child is referred with leukocoria in the right eye. The right eye shows no red reflex; instead a chalky white mass with calcium deposits is visible on B-scan. What is the diagnosis, what genetic counselling is needed, and what must NOT be done?
Answer: This is retinoblastoma — calcified intraocular mass in a child with leukocoria. Genetic counselling: test for germline RB1 mutation (heritable in ~40%; if germline, siblings and offspring at 50% risk and need screening; the patient themselves at risk for bilateral tumours and second primary cancers). What must NOT be done: fine needle aspiration biopsy of the tumour (risk of seeding the orbit and extraocular spread, which is potentially fatal). Treatment planning is done by ophthalmology oncology team under EUA.