Retina
The retina is where ophthalmology stops being a local subject. Diabetes, hypertension, atherosclerosis, prematurity and inherited disease all announce themselves here, and the fundus is the only place in the body where blood vessels and nerve tissue can be inspected directly.
The apparent difficulty is the number of conditions. The simplification is that the retina has two entirely separate blood supplies serving two different halves of its thickness, and knowing which half has failed predicts almost everything else.
1. Two Blood Supplies, Two Halves
| Layer | Supply | Contains |
|---|---|---|
| Inner retina | Central retinal artery | Ganglion cells, nerve fibre layer, inner nuclear layer |
| Outer retina | Choroid, across Bruch membrane | Photoreceptors and retinal pigment epithelium |
The organising tool is to ask which half is diseased. Diabetic retinopathy, vein occlusion and artery occlusion are diseases of the inner retinal circulation. Age-related macular degeneration and central serous retinopathy are diseases of the choroid, Bruch membrane and pigment epithelium.
The arrangement explains the most famous sign in the subject. In central retinal artery occlusion the infarcted inner retina turns white and opaque, but the fovea has no inner retina at all, being a pit where those layers are displaced aside. The choroidal circulation beneath it is unaffected and shows through as a cherry red spot.
It also explains retinal detachment. The neurosensory retina and the pigment epithelium develop from the two layers of the optic cup and never fuse firmly, so detachment separates them along an embryological plane, and the pigment epithelium stays behind with the choroid.
2. Reading the Fundus
The appearance of a haemorrhage tells you its depth, because the retinal architecture constrains its shape.
| Sign | Meaning |
|---|---|
| Flame haemorrhage | Nerve fibre layer, which is why it follows the axon bundles |
| Dot and blot haemorrhage | Deeper layers, where tissue is compact and vertically oriented |
| Cotton wool spot | Infarct of the nerve fibre layer with axoplasmic stasis, not an exudate |
| Hard exudate | Lipid left behind after fluid from leaking vessels reabsorbs |
| Drusen | Debris between the pigment epithelium and Bruch membrane |
A cotton wool spot is an infarct, not an exudate, and the misleading old name of soft exudate is why this is examined.
Hard exudates mark chronic leakage, and their circinate arrangement around a leaking focus is characteristic of diabetic maculopathy.
3. Diabetic Retinopathy
Chronic hyperglycaemia damages the retinal microvasculature, causing pericyte loss, capillary closure, and increased permeability. The consequences follow two independent tracks.
Ischaemia drives proliferation, because non-perfused retina releases vascular endothelial growth factor and new vessels grow. Leakage drives macular oedema, which is a separate axis and can occur at any stage.
| Stage | Findings |
|---|---|
| Mild non-proliferative | Microaneurysms only |
| Moderate non-proliferative | More than mild, less than severe |
| Severe non-proliferative | The 4-2-1 rule |
| Proliferative | New vessels on the disc or elsewhere, vitreous haemorrhage, tractional detachment |
The 4-2-1 rule defines severe non-proliferative disease: haemorrhages in four quadrants, venous beading in two quadrants, or intraretinal microvascular abnormalities in one quadrant.
Diabetic macular oedema is the commonest cause of visual loss in diabetes; proliferative disease is the commonest cause of severe loss. They are managed differently.
Anti-VEGF injection is first-line for centre-involving macular oedema. Panretinal photocoagulation is the standard for proliferative disease, destroying ischaemic peripheral retina to remove the stimulus for new vessels.
Anti-VEGF agents can also treat proliferative disease and are effective, but laser remains preferred where follow-up cannot be guaranteed, because a patient who stops attending after photocoagulation retains the treatment while one who stops attending after injections does not.
Screening
Diabetic retinopathy is asymptomatic until it is advanced, because neither peripheral ischaemia nor early new vessels affect vision, and this is the entire justification for screening.
Screening begins at diagnosis in type 2 diabetes, since the disease has usually been present for years before it is detected, and about five years after diagnosis in type 1, where the date of onset is known.
Pregnancy accelerates retinopathy, so a diabetic woman is examined in each trimester. Gestational diabetes does not carry the same risk, because the retinopathy reflects years of exposure rather than months.
4. Retinal Vein Occlusion
Branch occlusions occur at arteriovenous crossings, where the artery and vein share a common adventitial sheath, so a thickened arteriosclerotic artery compresses the vein against it. The field affected is the drainage territory of that vein.
Central retinal vein occlusion gives the classical picture of haemorrhages in all four quadrants, dilated tortuous veins, disc swelling and cotton wool spots.
The critical distinction is ischaemic against non-ischaemic, because it determines the risk of neovascularisation.
Ischaemic central retinal vein occlusion carries a high risk of neovascular glaucoma, classically around three months, which is why the condition is called ninety-day glaucoma. Poor acuity, a relative afferent pupillary defect and extensive capillary non-perfusion identify it.
Anti-VEGF treatment is used for the macular oedema, and panretinal photocoagulation for neovascularisation. Systemic assessment for hypertension, diabetes and hyperlipidaemia is mandatory, and in a young patient a thrombophilia screen is appropriate.
5. Retinal Artery Occlusion Is a Stroke
Central retinal artery occlusion presents with sudden painless total visual loss, a pale oedematous retina, a cherry red spot at the fovea, and segmentation of the blood column in the arterioles.
A cilioretinal artery, present in a minority of eyes, arises from the ciliary circulation and can preserve central vision by supplying the papillomacular bundle independently.
The most important recent change is conceptual. Acute retinal ischaemia is recognised by the American Heart Association and American Stroke Association as a stroke equivalent, requiring immediate multidisciplinary evaluation on a stroke pathway rather than referral to an eye clinic.
The scientific statement proposes thrombolysis time windows analogous to those in cerebral stroke, and randomised trials of intravenous thrombolysis are in progress. Two additions to the standard stroke code are specified: fundoscopy to confirm the diagnosis and exclude haemorrhage, and screening for arteritis.
The reasoning is straightforward. The central retinal artery is a branch of the ophthalmic artery, itself the first branch of the internal carotid, so an occlusion is embolic disease of the anterior circulation and carries a substantial early risk of cerebral stroke.
Amaurosis fugax is the transient equivalent, a curtain descending over the vision for minutes, and it is a transient ischaemic attack of the eye requiring the same urgency.
6. Outer Retinal Disease
This is disease of the outer retinal complex, meaning photoreceptors, pigment epithelium, Bruch membrane and choriocapillaris.
Dry, or non-neovascular, disease is characterised by drusen and progresses to geographic atrophy. It accounts for most cases and progresses slowly.
Wet, or neovascular, disease occurs when new vessels grow from the choroid through Bruch membrane, and it accounts for most severe visual loss. Onset is rapid, with distortion of straight lines.
Metamorphopsia is the symptom to act on, and the Amsler grid is how patients monitor for it at home, because subretinal fluid elevates the photoreceptor layer irregularly.
Intravitreal anti-VEGF injection is the treatment for neovascular disease, and it transformed the prognosis from inevitable central loss to stabilisation or improvement in most eyes.
For dry disease, AREDS-type supplementation slows progression in intermediate disease, and the reformulated combination replaced beta-carotene with lutein and zeaxanthin because beta-carotene increased lung cancer risk in smokers.
Central serous chorioretinopathy
The same anatomical compartment produces a very different disease in young adults.
Fluid leaks from the choroid through a defect in the pigment epithelium and collects under the neurosensory retina, elevating it as a shallow dome at the macula.
The patient is typically a man in his thirties or forties who reports a central grey patch, distortion, and objects appearing smaller in the affected eye. Acuity often improves slightly with a plus lens, because the elevated retina sits in front of its correct focal plane.
Corticosteroids in any form are the association that matters, along with type A personality and raised endogenous cortisol, and stopping exogenous steroid is often the whole treatment. Most episodes resolve spontaneously over a few months.
7. Retinal Detachment
| Type | Mechanism |
|---|---|
| Rhegmatogenous | A retinal break allows liquefied vitreous under the retina |
| Tractional | Fibrovascular membranes pull the retina off, as in proliferative diabetic retinopathy |
| Exudative | Fluid accumulates from choroidal or retinal disease without any break |
Rhegmatogenous detachment is the commonest and follows posterior vitreous detachment. As the vitreous liquefies with age and separates, traction at points of firm adhesion can tear the retina.
The symptoms follow the mechanism. Flashes come from mechanical traction stimulating photoreceptors, floaters from released pigment or blood, and a curtain or shadow from the detaching retina itself.
Whether the macula is still attached determines urgency. A macula-on detachment is an emergency, because surgery performed before the fovea detaches preserves central vision. A macula-off detachment has already lost that vision, and the timing becomes less critical.
Myopia is the major risk factor, along with previous cataract surgery, trauma and lattice degeneration.
8. Retinopathy of Prematurity
The premature retina is incompletely vascularised, and the peripheral avascular retina drives abnormal new vessel growth after birth.
Classification uses three axes: zone, meaning how far vascularisation has progressed, with zone I the most posterior and most dangerous; stage, from a demarcation line through ridge, extraretinal proliferation and detachment; and plus disease, meaning dilatation and tortuosity of posterior pole vessels, which signals activity.
India's screening criteria are deliberately broader than Western ones. All infants of 34 weeks gestation or less, or 2,000 grams or less at birth, are screened, and larger or more mature infants are screened if they have risk factors such as prolonged oxygen, sepsis, respiratory distress or transfusion.
The reason is explicitly stated in the national guidelines: the quality of neonatal care varies, and larger and more mature Indian babies develop severe disease that Western criteria would not capture. This pattern is described as the third epidemic of retinopathy of prematurity, occurring in middle-income countries with expanding neonatal survival but variable oxygen control.
The first examination is timed to catch disease before it becomes treatable-stage, conventionally within the first month of life, and screening then continues at intervals until the retina is fully vascularised.
Retinopathy of prematurity is now one of the conditions screened under the Rashtriya Bal Swasthya Karyakram.
Treatment is laser ablation of avascular retina, with anti-VEGF injection used particularly for posterior zone I disease, where laser is technically difficult and destroys a large area.
9. Inherited Retinal Disease
Retinitis pigmentosa is a rod-cone dystrophy, and every feature follows from rods being affected first.
Rods mediate vision in dim light and populate the mid-periphery, so the presentation is night blindness followed by a ring scotoma and progressive tunnel vision, with central acuity preserved until late.
The fundus shows bone-spicule pigmentation in the mid-periphery, attenuated arterioles and waxy pallor of the disc. Posterior subcapsular cataract and cystoid macular oedema are common associations.
The electroretinogram is reduced or extinguished before the fundus looks abnormal, which makes it the earliest objective test and the answer to questions about early diagnosis.
10. Retinoblastoma
Retinoblastoma is the commonest intraocular malignancy of childhood and the one condition in this chapter that kills.
It arises from biallelic inactivation of the RB1 tumour suppressor gene on chromosome 13, and Knudson's two-hit hypothesis was formulated from it.
Heritable disease carries one mutation in every cell, so it presents earlier, is frequently bilateral and multifocal, and carries a lifelong risk of second malignancies, particularly osteosarcoma. Trilateral retinoblastoma describes an associated intracranial primitive neuroectodermal tumour, usually pineal.
Presentation is with leukocoria or strabismus, and any child with either requires urgent examination under anaesthesia.
Ultrasound shows intralesional calcification, which is the key discriminator from the other causes of leukocoria.
Biopsy is absolutely contraindicated, because breaching the globe seeds tumour extraocularly and converts a curable intraocular cancer into a systemic one.
11. Infectious Retinitis
Two infections produce retinitis often enough to be examined, and both are diagnosed on appearance rather than serology.
Toxoplasma retinochoroiditis is the commonest cause of posterior uveitis. It presents as a focal white retinal lesion beside an old pigmented scar, because reactivation occurs at the margin of a congenital or previously acquired lesion.
Overlying vitritis is dense enough to produce the classical description of a headlight in the fog. Treatment is reserved for sight-threatening lesions near the macula or disc, since peripheral lesions resolve on their own.
Cytomegalovirus retinitis occurs in profound immunosuppression, classically with a CD4 count below 50, and is the commonest ocular opportunistic infection in advanced HIV.
The appearance is a haemorrhagic necrotising retinitis spreading along the vessels, described as a pizza or cottage cheese and ketchup fundus. It is painless and progresses relentlessly without treatment, and immune reconstitution with antiretroviral therapy is as important as the antiviral itself.
Acute retinal necrosis is the immunocompetent counterpart, caused by varicella zoster or herpes simplex, and it differs by being painful, rapidly progressive from the periphery, and associated with occlusive arteritis.
12. Hypertension and the Fundus
Hypertensive retinopathy progresses through arteriolar narrowing, then arteriovenous nipping and copper or silver wiring, then flame haemorrhages, cotton wool spots and hard exudates, and finally disc swelling.
Disc swelling indicates malignant hypertension and is a medical emergency, requiring controlled blood pressure reduction rather than an ophthalmic intervention.
A macular star of hard exudates radiating from the fovea reflects leakage tracking along the radially arranged Henle fibre layer.
13. Worked Examples
Example 1. A 65-year-old has sudden painless complete loss of vision in one eye. The retina is pale with a cherry red spot. Where should this patient be managed?
On a stroke pathway. Central retinal artery occlusion is recognised by the American Heart Association as a stroke equivalent, because the central retinal artery is a branch of the internal carotid circulation and the event is embolic anterior circulation disease with a substantial early risk of cerebral stroke. Fundoscopy confirms the diagnosis and excludes haemorrhage, and arteritis must be screened for, since giant cell arteritis is an alternative cause requiring immediate steroid.
Example 2. A diabetic has haemorrhages in all four quadrants, venous beading in two and intraretinal microvascular abnormalities in one. Classify and manage.
This satisfies the 4-2-1 rule and is severe non-proliferative diabetic retinopathy, meaning a high rate of progression to proliferative disease. It is not yet proliferative, since there are no new vessels. Close follow-up is required, with panretinal photocoagulation considered early where follow-up is uncertain, and the macula must be assessed separately for centre-involving oedema, which is treated with anti-VEGF regardless of the retinopathy stage.
Example 3. A 2-year-old has a white pupillary reflex, and ultrasound shows a mass with calcification. What must not be done?
A biopsy. This is retinoblastoma, and breaching the globe seeds tumour into the orbit and beyond, converting an intraocular cancer with excellent survival into systemic disease. Diagnosis is made clinically under anaesthesia with imaging, calcification being the discriminating feature. Both eyes and the brain must be assessed, given the possibility of bilateral heritable disease and trilateral retinoblastoma.
Example 4. A preterm infant born at 35 weeks weighing 2,100 grams received prolonged oxygen and had sepsis. Does Indian guidance require screening?
Yes. Although the infant exceeds both the 34 week and 2,000 gram thresholds, national operational guidelines require screening of more mature and heavier infants who have risk factors, including prolonged oxygen therapy, sepsis, respiratory distress, transfusion and cardiorespiratory support. The criteria are deliberately broader than Western ones because variability in neonatal care means larger Indian babies develop severe disease.
Summary
Two blood supplies, two halves. The central retinal artery serves the inner retina; the choroid serves photoreceptors and pigment epithelium.
The cherry red spot exists because the fovea has no inner retina, so the choroid shows through infarcted surroundings.
Haemorrhage shape reveals depth, and a cotton wool spot is an infarct rather than an exudate.
In diabetes, ischaemia drives proliferation and leakage drives oedema, and the two are separate axes.
The 4-2-1 rule defines severe non-proliferative disease.
Anti-VEGF treats macular oedema; panretinal photocoagulation treats proliferation, and laser is preferred where follow-up is unreliable.
Branch vein occlusions happen at arteriovenous crossings, and ischaemic central occlusion causes ninety-day glaucoma.
Retinal artery occlusion is a stroke equivalent and belongs on a stroke pathway, with arteritis screened for.
Wet macular degeneration is choroidal neovascularisation presenting with distortion and treated with anti-VEGF.
Central serous chorioretinopathy is the young man's outer retinal disease, driven by steroid in any form and usually self-limiting.
Toxoplasma retinochoroiditis reactivates beside an old scar, cytomegalovirus retinitis appears below a CD4 count of 50, and acute retinal necrosis is the painful immunocompetent counterpart.
Rhegmatogenous detachment follows posterior vitreous detachment, and a macula-on detachment is the emergency.
Indian ROP screening is deliberately broader, at 34 weeks or 2,000 grams, with risk-factor screening above that.
Retinitis pigmentosa is rod-first, and the electroretinogram is abnormal before the fundus is.
Never biopsy a retinoblastoma.
