Diseases Of The Retina

Diseases Of The Retina

CONGENITAL AND DEVELOPMENT
DISORDERS

Coloboma of the optic disc

• Results from failure of the embryonic fissure closure.
• Minor defect manifests as inferior crescent, usually associated with hypermetropia or astigmatism.

Drusen of the optic disc

• Lies deep beneath the surface of the disc tissue in childhood (presents as pseudopapilloedema) and emerges out by the early teens presenting as waxy pea-like irregular refractile bodies.

Hypoplasia of the optic disc

• An important cause of blindness at birth in developed countries (rare in developing countries).
• Associated with maternal alcohol use, diabetes and use of certain drugs in pregnancy.
• Bilateral in 60 percent cases.
• Small disc with ‘double ring sign’ is pathognomonic.

Medullated nerve fibres

• Represent myelination of nerve fibres of the retina (normally myelination stops at lamina cribrosa).
• Appear as whitish patch with feathery margins, usually present around the disc and may cause enlargement of the blind spot.
• Disappear in patients with optic atrophy.

Congenital remnants of the hyaloid arterial system

• Bergmester’s papilla—a flake of glial tissue projecting from the disc (commonest anomaly of the hyaloid system)
• Mittendorf dot—remnant of anterior end of hyaloid artery attached to the posterior lens capsule, usually associated with a posterior polar cataract.

Diseases Of The RetinaINFLAMMATIONS OF THE RETINA

Retinitis
Subacute retinitis of Roth typically occurs in patients with subacute bacterial endocarditis (SABE) and is characterised by Roth’s spots (superficial haemorrhages with a white spot in the centre).
• Cytomegalovirus (CMV) retinitis and herpes zoster retinitis are more common in patients with AIDS.

Periphlebitis retinae
• Primary periphlebitis retinae (Eales’ disease) is considered a hypersensitive reaction to tubercular proteins.
• Secondary periphlebitis occurs in patients with uveitis.
• Eales’ disease is a bilateral condition, affecting young adult males. It is characterised by recurrent primary vitreous haemorrhages.
Complications of Eales’ diseases include— rubeosis iridis, neovascular glaucoma, proliferative retinopathy and fractional retinal detachment.

VASCULAR DISORDERS OF THE RETINA
Retinal artery occlusions

Central retinal artery occlusion (CRAO)

• It occurs due to obstruction at the level of lamina cribrosa.
• Causes sudden painless loss of vision (central vision not affected in patients with cilio-retinal artery).
• Retina becomes white due to oedema and a ‘Cherry-red-spot’ is seen at the fovea.
• Arterioles become narrow and blood column within the retinal vessels is segmented (Cattle-truck appearance).
• Resuscitation time of the human retina following retinal ischaemia is 1 1/2 hours.

Branch retinal artery occlusion (BRAO)

• Occurs following lodgement of embolus at a bifurcation.
• Retina distal to the occlusion becomes oedematous with narrowing of arterioles.
• Later on involved area is atrophied leading to permanent sectorial field defect.

Retinal vein occlusion

• Predisposing factors are hypertension, open-angle glaucoma, polycythemia, and periphlebitis.
• Non-ischaemic central retinal vein occlusion (CRVO) is most common variety (75%), characterised by mild to moderate visual loss.
• Ischaemic central retinal vein occlusion is characterised by much more marked signs and symptoms than non-ischaemic CRVO.
• Complicationi are neovascular glaucoma (NVG) occurs in more than 50 per cent cases within 3 months, vitreous haemorrhage, and proliferative retinopathy.
• Branch retinal vein occlusion: the superotem- poral branch is the most commonly affected (33%).

Hypertensive retinopathy

Scheie’s grading of hypertensive retinopathy
Grade I : Mild generalized narrowing of arterioles
Grade II : Marked generalized narrowing plus focal constriction of arterioles.
Grade III : Grade II changes plus haemorrhages, cotton-wool spots and hard exudates.
Grade IV : Grade III changes plus papilloedema.

Scheie’s grading of arteriosclerotic changes

Grade 1 : Broadening of arteriolar reflex due to sclerosis of the walls.
Grade II : Grade I changes plus arteriovenous crossing changes.
Grade III : Grade II changes plus copper wire appearance of arterioles.
Grade IV : Grade III changes plus silver wire appearance of arterioles.

Retinopathy in toxaemia of pregancy

• Earliest changes consist of narrowing of nasal arterioles followed by generalised narrowing.
• Advent of hypoxic changes (cotton wool spots, haemorrhages and retinal oedema) should be considered an indication for termination of pregnancy.

Diabetic retinopathy

Risk factors
• Duration of diabetes: Incidence is about:
– 50 percent after 10 years of diabetes,
– 70 percent after 20 years of diabetes and
– 90 percent after 30 years of diabetes
Heredity: effect is more on proliferative DR, transmission is recessive
• Sex: Male: Female:: 3:4
Pregnancy: Accentuates the changes of DR
Hypertension: Accentuates the changes of DR.

Classification

1. Non-proliferative diabetic retinopathy (NPDR) Signs

• Microaneurysms (an early sign)
• Dot and blot haemorrhages
• Hard exudates
• Retinal thickening due to diffuse oedema
• Venous abnormalities beading, looping and dilatation
• Cotton-wool spots
• Intraretinal microvascular abnormalities (IRMA)
Treatment is not required, management includes:
• Adequate control of diabetes
• Annual fundus examination

2. Diabetic maculopathy

Focal exudative maculopathy
• Characterized by changes of NPDR and hard exudates arranged in a circinate pattern in macular area.
• Fluorescein angiography reveals focal leakage with adequate macular perfusion.
• Treatment consists of focal argon laser to microaneurysms and centre of the hard exudates ring.

Diffuse exudative maculopathy
• Changes of NPDR with very few hard exudates in the macular area
• Diffuse retinal oedema and thickening throughout the posterior pole
• Cystoid macular oedema and lamellar hole in long standing cases
• Fluorescein angiography shows diffuse leakage but good macular perfusion.
• Treatment consists of grid pattern argon laser photocoagulation

Ischaemic maculopathy
• Marked visual loss
• Microaneurysms, haemorrhages, mild or no oedema and only a few hard exudates if any
• Fluorescein angiography shows poor macular perfusion.

Mixed maculopathy
• Features of combined ischaemic and exudative maculopathy are present.

3. Proliferative diabetic retinopathy

Signs of PDR: In chronological order, over and above the signs of NPDR are as follows:
• Neovascularization on the disc (NVD) or elsewhere (NVE)
• Incomplete posterior vitreous detachment
• Elevation of new vessels and vitreous haemorrhage
• Fibrovascular epiretinal membrane
• Tractional retinal detachment.

Treatment: Panretinal argon photocoagulation.

4. Advanced diabetic eye disease

• Persistent vitreous haemorrhage
• Tractional retinal detachment
• Neovascular glaucoma
• Treatment – is pars plana vitrectomy

Sickle-cell retinopathy
• Retinal changes are caused by hypoxia resulting from blockage of small blood vessels by the abnormal shaped rigid red blood cells.

Clinical features
• Stage I : Peripheral arteriolar occlusion
• Stage II : Peripheral arteriovenous anastomosis
• Stage III : Neovascularization
• Stage IV : Vitreous haemorrhage
• Stage V : Vitreo-retinal traction bands and tractional retinal detachment.

Treatment
• Pan retinal photocoagulation (PRP) is effective in regressing the neovascularization.
• Pars plana vitrectomy for stage IV and V.

Anaemic retinopathy
• Changes appear when haemoglobin falls below 5 gm per cent.
• Pale background and pale arterioles
• Dilated veins
• Superficial haemorrhages and subhyaloid haemorrhage
• A few Roth’s spots and cotton wool spots

Leukaemic retinopathy
• Pale and orange fundus background
• Dilated and tortuous veins
• Superficial haemorrhages, Roth’s spots and subhyaloid haemorrhage.
• Perivascular leukaemic infiltration

Retinopathy of prematurity (retrolental fibroplasia)
• Occurs in premature infants (weighing less than 1300 gm) exposed to high concentration of oxygen.
It is an important cause of leukocoria in chidren.

Clinical features:
• Stage 1 : Formation of demarcation line
• Stage 2 : Formation of retinal ridge
• Stage 3 : Ridge with extraretinal fibrovascular proliferation.
• Stage 4 : Subtotal fractional retinal detachment
• Stage 5 : Total retinal detachment.

Management
• Oxygen concentration in incubator should be kept less than 30 percent.
• Regular screening by indirect ophthalmoscopy between 2 and 4 months of life is most important
• Ablation of peripheral avascular retina with cryopexy or photocoagulation when neovas-cularization is detected
• Pars plana vitrectomy for tractional retinal detachment.

DYSTROPHIES AND DEGENERATIONS OF THE RETINA

Retinitis pigmentosa

Inheritance
• Autosomal recessive – most common and most evere
• Autosomal dominant – common and relatively benign
• Sex linked — least common, relatively severe

Incidence
• 5 persons per 1000 of the world population
• Male:female ratio is 3 : 2
• Bilateral equal involvement

Clinical features
Night blindness – may occur before the retinal changes, appear.

Fundus changes
• Retinal pigmentary changes occur in the form of perivascular deposition of bony corpuscle pigments in the equatorial region; which later spread both anteriorly and posteriorly
• Retinal arterioles are attenuated
• Optic disc becomes pale waxy ending in consecutive optic atrophy.

Visual field changes
• Annular or ring scotoma
• Tubular vision in advanced cases.

Electrophysiological changes
• Appear even before the subjective symptoms and signs
• ERG is subnormal or abolished
• EOG is extinguished

Ocular associations
• Myopia (common)
• Primary open-angle glaucoma in 30 percent
• Microphthalmos
• Keratoconus (rare)
• Subcapsular cataract.

Systemic associations

Laurence-Moon-Biedi syndrome (most common)
• Retinitis pigmentosa
• Obesity
• Hypogenitalism
• Polydactyly
• Mental deficiency

Cockayne’s syndrome
• Retinitis pigmentosa
• Nystagmus
• Progressive infantile deafness
• Dwarfism
• Mental retardation
• Ataxia

Refsum’s syndrome
• Retinitis pigmentosa
• Peripheral neuropathy
• Cerebellar ataxia

Usher’s syndrome
• Retinitis pigmentosa
• Labyrinthine deafness

Hallgren’s syndrome
• Retinitis pigmentosa
• Vestibulo-cerebellar ataxia
• Congenital deafness
• Mental deficiency

Atypical forms of retinitis pigmentosa
Retinitis pigmentosa sine pigmento: All features of retinitis pigmentosa, except no or minimal visible pigmentary changes.
Sectorial retinitis pigmentosa: Only one quadrant (usually nasal) or one half (usually inferior) is involved
Pericentric retinitis pigmentosa: Pigmentary changes are confined to an area immediately around the macula
Retinitis punctata albescens: Innumerable discrete white dots are scattered over the fundus.

MACULAR DISORDERS
Photoretinitis
• Damage of the foveolar region caused by ultraviolet ray and infra-red rays of bright sun¬light, commonly occurring during solar eclipse (Eclipse burn)
• Typical lesion appears as a bean or kidney shaped pigmented spot with yellowish white centre in the foveal region.

Central serous retinopathy (CSR)
• It refers to spontaneous detachment of neurosensory retina in the macular region
• Typically affects males between 20 and 40 years causing sudden painless mild loss of vision (6/9- 6/12), metamorphopsia and relative positive scotoma
• Fluorescein angiography may show ‘ink-blot’ or ‘smoke-stack’ sign
• Self-limiting (90%) but recurrent (40%)
• Laser photocoagulation is indicated in:
– long standing cases (more than 4 months)
– patients showing multiple leaks
– impaired visual acuity in the fellow eye from CSR.

Cystoid macular oedema
• Collection of fluid in the outer plexiform (Henle’s layer) and inner nuclear layer of the retina, centred around fovea due to break down of the inner blood-retinal barrier.

Causes
• Postoperative complication of cataract and keratoplasty operations.
• Inflammations such as pars planitis, and posterior uveitis
• Retinal vascular disorders, diabetic retinopathy, and retinal vein occlusion.
• Retinal dystrophy – Retinitis pigmentosa
• Side effect of topical 2% adrenaline in aphakic patients.
• Secondary to other maculopathies
• Complication of peripheral retinal photocoagulation.

Clinical features
• Minimal to moderate loss of vision which may be permanent in persistent cases
• Typical fundus picture in advanced cases is of ‘Honey-comb appearance’ of macula
• Fluorescein angiography in well established cases presents a ‘flower-petal appearance’
• Long standing CME may end in macular hole.

Age-related macular degeneration (AMD)

Non-exudative AMD
• Also called as dry or geographical AMD
• Comparatively common (90% cases) and causes gradually progressive mild to moderate loss of vision
• Fundus shows: colloid bodies, pale areas of retinal pigment epithelium (RPE) atrophy, and irregular or clustered pigmentation.

Exudative AMD
• Also called as wet or neovascular AMD.
• Comparatively rare (10% cases) but causes progressive and marked loss of vision.
• Clinical course rapidly passes through following stages:
– Stages of drusen formation
– Stage of detachment of RPE.
– Stage of subretinal neovascular membrane (SRNVM)
– Stage of haemorrhagic detachment of RPE.
– Stage 6f haemorrhagic detachment of neurosensory retina
– Terminal stage of disciform macular scarring (degeneration)
Laser photocoagulation is indicated for an extrafoveal SRNVM situated 200 µ or more from the centre of fovea.

Heredomacular degenerations

Best’s disease
• Autosomal dominant

Clinical picture – five stages:
Pre-vitellifonn stage: Normal fundus but EOG is abnormal.
Vitelliform stage: Egg yolk lesion at macula.
Pseudohypopyon stage: Partially absorbed egg yolk lesion.
Vitelliruptive stage: A scrambled egg appearance at macula
Stage of scarring: hypertrophic, atrophic or vascularized scar at macula.

Stargardt’s disease
• Presents with decreased vision in first or second decade of life.
• Typical fundus picture is ‘beaten-bronze’ or ‘snail- slime reflex’ in the macular area.

RETINAL DETACHMENT

Retinal detachment (RD) refers to separation of neurosensory retina from the retinal pigment epithelium (RPE).

I. Rhegmatogenous RD

Predisposing factors
• Age – Most common 40-60 years (no bar)
• Sex – Male: Female:: 3: 2
• Myopia – 40 percent cases
• Aphakia
• Retinal degenerations such as:
– Lattice degeneration (most common)
– Snail track degeneration
– White-with-pressure and white-without pressure lesions
– Diffuse chorioretinal degenerations
– Acquired (senile) retinoschisis
• Trauma
• Senile posterior vitreous detachment (PVD)

Clinical features
Prevalence
Affects 1 in 1000 population each year

Prodromal symptoms
• Photopsia (flashes of light) due to vitreo-retinal traction
• Dark spots (floaters) in front of the eyes

Symptoms of detached retina
• Localized relative loss in the field of vision of detachment retina
• Loss of vision in detachments involving macular area.

Signs
• Detached retina gives grey reflex, is raised, thrown into folds which oscillate with the movements of the eye
• Retinal breaks (round, horse-shoe-shape or slit like) look reddish and are most frequently found in the periphery (commonest in the upper temporal quadrant)
• Signs of old RD are:
– thinning of the detached retina
– secondary intraretinal cysts
– subretinal demarcation lines (high water marks).

Management
Indications of prophylactic treatment
• Symptomatic retinal breaks associated with PVD
• Large asymptomatic retinal tears
• Asymptomatic retinal break and/or lattice degeneration in the presence of: aphakia, high myopia, only eye, RD in fellow eye, strong family history’ of RD, and Marfan’s syndrome, Stickler’s syndrome and Ehlers-Danlos syndrome.

Basic principles of treatment
1. Sealing of retinal breaks: It is commonly performed with cryopexy.
2 Bringing the sclera, choroid and detached retina with each other. It is carried out by the procedure of scleral buckling or encirclage.

Indications for drainage of subretinal fluid (SRF)
• Difficulty in localizing retinal breaks in bullous RD
• Longstanding (old) RD
• RD with inferior breaks
• RD with immobile retina
• RD with advanced glaucoma, thin sclera and recent cataract extraction.

II. Exudative or solid retinal detachment

Retina is elevated due to accumulation of fluid beneath it, associated with RPE damage:
Causes
1. Systemic diseases
• Toxaemia of pregnancy
• Renal hypertension
• Blood dyscrasias
• Polyarteritis nodosa.

2. Ocular diseases
(i) Inflammations
• Harada’s disease
• Sympathetic ophthalmitis
• Posterior scleritis
• Orbital cellulitis
(ii) Vascular diseases
• Exudative retinopathy of coats
• Central serous retinopathy
(iii) Neoplasms
• Retinoblastoma (exophytic)
• Malignant melanoma of choroid
(iv) Sudden hypotony following:
• Globe perforation
• Intraocular operation

Clinical features
Exudative RD can be differentiated from rhegmato- genous RD by following characteristics:
• Absence of photopsia
• Absence of retinal breaks, folds and undulations
• Configuration of the RD is convex
• Shifting fluid sign is pathognomic of exudative RD
• On transillumination, rhegmatogenous RD is transparent while exudative RD is opaque.

III. Tractional retinal detachment

It occurs due to retina being mechanically pulled away from its bed by the progressive contraction of fibrous or fibrovascular membrane over large areas of vitreo-retinal adhesions (vitreo-retinal traction bands).

Causes
• Post-traumatic retraction of scar tissue
• Proliferative diabetic retinopathy
• Sickle-cell retinopathy
• Retinopathy of prematurity
• Eales’ disease
• Plastic cyclitis
• Post-vitreous haemorrhage retinitis proliferans

Clinical features
• Presence of vitreo-retinal traction bands with lesions of the causative disease
• Configuration of the detached retina is concave
• Absent — photopsia, floaters, retinal breaks, shifting fluid sign, mobility of detached retina

TUMOURS OF RETINA
Retinoblastoma
Incidence
• Most common intraocular tumour of childhood
• Occurs in 1 in 14000-34000 live births.
• Age — Usually presents at 18 months (1-2 years)
• Rare in Negroes
• 25-30 percent cases are bilateral

Heredity
1. Sporadic cases (no family history in 94%), usually unilateral and unifocal
2. Familial cases (6%), occur by autosomal dominant inheritance with incomplete penetrance (70-80%), usually bilateral and multifocal.

Familial cases are predisposed to develop second non-ocular malignancy including pinealoblastoma and osteogenic sarcoma. Bilateral retinoblastoma with pinealoblastoma is known as trilateral retinoblastoma. Knudson’s two-hit theory/hypothesis (1971)
• Retinoblastoma occurs by two mutations (hits)
• In hereditary cases, first hit (mutation) occurs in one of the parental germ cells before fertilization and thus involves all the somatic cells of the body (germinal mutation). Second hit occurs later in post-zygotic phase in retinal cells (somatic mutation) causing retinoblastoma.
• In non-hereditary cases, both hits (mutations) occur in the embryo after fertilization involving the same retinal cell and thus cause retinoblastoma.

Pathology
• Arises from the immature retinal neural cells
• Histologically, cells may present as highly undifferentiated or well differentiated tumour
• Features of well-differentiated tumour include:
– Flexner-Wintersteiner rosettes (highly specific for retinoblastoma).
– Homer-Wright rosettes (Also seen in neuroblastoma and medulloepithelioma)
– Pseudorosettes
– Fleurettes
• Other histological features of retinoblastoma are:
– Areas of necrosis
– Calcification

Presenting features
• Leukocoria(61%)
• Squint (22%)
• Nystagmus in bilateral cases
• Secondary glaucoma and buphthalmos (rare)
• Pseudohypopyon (rare)
• Anterior chamber inflammation which may mimic anterior uveitis (rare)
• Hyphaema (rare)
• Proptosis which may mimic orbital cellulitis (rare)

Fundus examination in early stage (before leukocoria) may show:
Endophytic retinoblastoma which grows inwards and is white or pearly pink in colour. Fine blood vessels may be present on its surface. In the presence of calcification, it gives the typical ‘cottage-cheese’ appearance.

Exophytic retinoblastoma which grows outwards and causes exudative retinal detachment.

Investigations
• Plain X-rays, orbit— may show calcification in 75% cases.
• Ultrasonography and CT scanning are quite useful.
• Lactic dehydrogenase (LDH) levels are raised in aqueous humour.

Differential diagnosis
Differential diagnosis of leukocoria
• Congenital cataract
• Retinopathy of prematurity
• Persistent hyperplastic primary vitreous
• Toxocara endophthalmitis
• Coats’ disease
• Coloboma of choroid
• Retinal dysplasia.

Differential diagnosis of endophytic retinoblastoma discovered on fundus examination:
• Patch of exudative choroiditis
• Astrocytoma

Differential diagnosis of exophytic retinoblastoma causing exudative retinal detachment:
• From other causes of exudative RD

Treatment
Enucleation
• It is treatment of choice for intraocular tumour of more than 10 mm in size or when optic nerve is involved.
• The eyeball should be enucleated with maximum length of the optic nerve and taking care not to perforate it.

Conservative (tumour destructive) therapy
• It is indicated when tumour is less than 10 mm in size and optic nerve is not involved
• Modalities include:
– Cobalt plaques: for small peripheral tumour.
– Cryotherapy: for small peripheral tumour. Argon, diode or xenon arc potocoagulation: for small posterior tumours not invading either the macula or the optic nerve

Debulking of the orbit with radiotherapy and chemotherapy are used as palliative measures.
• For clinical stage III and IV.
Chemotherapy includes etoposide, carboplatin, vincristine and cyclosporin.

Prognosis
• Fair (survival rate 70-85%) if eyeball is enucleated, before the extraocular extension.
• Poor prognostic factors are:
– Optic nerve involvement beyond the transection (65% mortality).
– Undifferentiated tumour cells (40% mortality) fete; Massive choroidal invasion

Phakomatoses
1. Angiomatosis retinae (von Hippel-Lindau’s disease)
• Angiomatosis involves retina, brain, spinal cord, kidneys and adrenals
• Retinal lesions comprise vascular dilatation, tortuosity and formation of aneurysms which vary from small miliary to balloon-like angiomas, followed by appearance of haemorrhages and exudates, resembling exudative retinopathy of Coats’. Massive exudation is frequently complicated by retinal detachment.

2. Tuberous sclerosis (Bourneville disease)
Classic diagnostic triad includes:
• Adenoma sebaceum
• Mental retardation
• Epilepsy associated with potato-like hamartomas of the brain, retina and viscera.

3. Neurofibromatosis (Von Recklinghausen’s disease)
• Multiple tumours of skin, nervous system and other organs
• Cutaneous manifestations vary from cafe-au-lait spots to neurofibromata
• Ocular manifestations include: neurofibromas of lids and orbit, glioma of optic nerve and congenital glaucoma.

4. Encephalofacial angiomatosis (Sturge-Weber syndrome) Characterised by angiomatosis in the form of port wine stain (Naevus flammeus) involving one side of the face which may be associated with choroidal haemangiomas, leptomeningeal angioma and congenital glaucoma on the affected side.

MISCELLANEOUS POINTS
• Superficial retinal haemorrhages are most commonly associated with hypertension.
• Pseudoxanthoma elasticum is the most common systemic disorder association with angioid
streaks; other causes are: macular degeneration, Paget’s disease. Gronblad-strandberg syndrome, senile elastosis.
• Angioid streaks:
– may be mistaken for blood vessels
– are usually situated near the disc
– are situated at a deeper level than retinal vessels
– result due to defects in Bruch’s membrane.
• Rods are primarily affected in retinitis pigmentosa.
• Lattice degeneration most commonly occurs in the superotemporal quadrant.
• Salt and pepper fundus is characteristic of congenital syphilitic retinal affection. It is also seen in Leber’s amaurosis and congenital rubella.
• Bull’s eye macular lesions are seen in chloroquine retinopathy and progressive cone dystrophy.
• Reversal of diabetic retinopathy is seen in a woman with Sheehan’s syndrome (due to lack of growth hormone).
• Colour vision is not significantly impaired in eyes with early macular disease, in contrast to eyes with early lesions of optic nerve.
• Macular star may occur in hypertensive retinopathy, papilloedema and Eales’ disease.
• Flame-shaped superficial haemorrhages occur in the nerve fibre layer of the retina.
• Retinoblastoma is the most common retinal malignancy.
• Retinoblastoma is the most common primary malignant intraocular tumour of childhood and the second most common primary intraocular malignancy of all age groups (Choroidal melanoma is more common).
• The most common mode of metastasis of retinoblastoma is by direct extension, by continuity to the optic nerve.
• The most common site of metastasis of retinoblastoma is brain.