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Systemic Disease and the Eye. Dr Sancy Low. Background. Patients of all ages and medical history can present with eye problems Symptoms are often associated with systemic disease

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Systemic Disease and the Eye

Dr Sancy Low


  • Patients of all ages and medical history can present with eye problems

  • Symptoms are often associated with systemic disease

  • Cardiovascular, endocrine, rheumatoid, connective tissue disease, inherited eye disease and HIV are prominent examples

Topics covered in this lecture

  • Diabetic Retinopathy

  • Hypertensive Retinopathy

  • Thyroid Eye Disease

  • Inherited Eye Disease

  • HIV and AIDS

Diabetic Retinopathy (DR)

Diabetic Retinopathy (DR)

  • Microvascular disease of the retinal microcirculation

  • Commonest cause of blindness under 65y

  • Symptom less until loss of vision :

    • Gradual = Central (macula) area of retina involved by oedema, exudates or haemorrhage (maculopathy)

    • Sudden = vitreous haemorrhage from new blood vessels (proliferative DR)



  • Glycosylation of proteins (capillary basement membranes)

  • Loss of endothelial supporting cells (pericytes)

  • Microaneurysms (hallmark of disease) = leakage

  • Capillary closure = ischaemia

Type 2 diabetes


Background diabetic retinopathy


Type 1 diabetes


Background diabetic retinopathy

Pre-proliferative diabetic retinopathy


Vitreous haemorhage

Tractional retinal detachment

Background DR


  • Microaneurysms / haemorrhages (‘dots and blots’)

  • Exudates

    Treatment:- Observe



Background DR changes but in the macula area


  • Argon Green laser (induces thermal burn)

  • Either focal or grid laser photocoagulation

Pre-proliferative DR


  • Cotton wool spots

  • Extensive haemorrhages

  • Venous beading

  • Intraretinal microvascular abnormalities (IRMA)

Pre-proliferative DR


Close observation

Proliferative DR: new vessel formation

Treatment:Argon laser panretinal photocoagulation (PRP)

Panretinal photocoagulation

3 days post treatment

Old burns

Laser burns: Destroy retina in PRP

End Stage Disease: fibrosis, retinal traction and eventual detachment

End Stage Disease: retinal detachment

Summary: Diabetic Retinopathy

Prevention of DR

  • Progressive disease

    • Type I DM: 25% affected by 10y

    • Type II DM: 50% affected by 10y

  • Regular eye tests: Optician, GP, Diabetic team, Ophthalmologists

  • BM control (DCCT)

  • BP control (UKPDS)

  • Stop smoking

Hypertensive retinopathy

Hypertensive retinopathy

  • Has been graded 1 to 4 (but not satisfactory!)

    • Grade 1: arteriolar narrowing and vein concealment

    • Grade 2: severe arteriolar attenuation and venous deflections at crossings (AV nipping)

    • Grade 3: arteriolar copper wiring, haemorrhages, CWS and hard exudates

    • Grade 4: all of the above plus silver wiring and optic disc swelling


  • Systemic hypertension

    • Early signs difficult to tell from ageing changes

  • Malignant hypertension

    • Accelerated severe hypertension causing encephalopathy and papilloedema (sign of raised intracranial pressure)

Mild to moderate chronic hypertensive retinopathy

Arterial and venous changes with some haemorrhages

Severe disease with cotton wool spots (ischaemia)

Note black areas of non-perfusion on FFA (fundus fluorescein angiogram)

Malignant hypertension - papilloedema, ischaemia, infarction and macular star


  • Treat the hypertension!

  • Watch out for other complications such as central retinal artery and central retinal vein occlusions (acute visual loss lecture)

Thyroid Eye Disease

Thyroid Eye Disease (aka Grave’s Ophthalmopathy)

  • Associated with thyrotoxicosis (but patient can be clinically and biochemically euthryoid)

  • Organ specific IgG mediated disease

  • Infiltration of muscles and fat surrounding eye

  • Unilateral or bilateral

  • Two stages:

    • Acute inflammatory (risk of sight loss); lasts approx 12-18 months

    • Chronic fibrotic

Conjunctival chemosis (oedema)

Eyelid retraction (worse on downgaze)

Diplopia (usually upgaze +/- lateral gaze)


Corneal exposure (corneal ulcers if severe)

Compressive optic neuropathy: decreased V/A, RAPD, field loss, reduced colour vision


TED symptoms

  • Nil

  • Grittiness

  • Redness

  • Eyelid swelling

  • Diplopia

  • Cosmetic appearance “bulgy eyes”

  • Visual loss

American Thyroid Association Classification

  • NOSPECS – 6 stages

    • (0) No signs or symptoms

    • (1) Only ocular irritation (dryness, FB)

    • (2) Soft tissue involvement (oedema)

    • (3) Proptosis

    • (4) EOM (extraocular muscle) involvement

    • (5) Corneal involvement

    • (6) Sight loss

Investigation: CT orbit Proptosis and EOM infiltration(medial & inferior rectus most commonly involved)


  • Manage thyroid dysfunction

  • Ocular lubricants alone (in mild cases)

  • Acute optic nerve compression & corneal exposure

    • Systemic corticosteroids

    • Radiotherapy

    • Surgical orbital decompression

  • Chronic phase

    • Diplopia: Squint surgery, Prisms, Botulinum toxin

    • Cosmetic: Orbital decompression; lid surgery eg blepharoplasty, lid lowering etc

Inherited eye diseasee.g. Retinitis Pigmentosa

Inherited eye disease

  • Genetic eye disease accounts for 20% of blind registration in young adults

  • 40-50% of blindness in children is inherited

  • Retinitis Pigmentosa is the commonest inherited retinal dystrophy

  • Affects 1:5000 of the population

  • It is a heterogeneous condition which primarily affects the retinal rods and later retinal cones

Retinitis Pigmentosa

  • Bone-spicule pigmentation around blood vessels

  • Pale waxy appearance or the peri-papillary retina


  • RP can be inherited in all forms: AR, XL, AD, and mitochondrial or simplex (where there is no other known family history)

  • Patients usually present with night blindness but can progress to tunnel vision and total blindness (as rods then cones are affected)

  • Syndromic forms of RP exist e.g. Usher syndrome = night blindness and deafness (usually recessive)

Photoreceptor loss

  • Progressive disease

  • Loss of rods first

  • Cone loss eventually

  • Night blindness first then peripheral field loss, tunnel vision and eventual blindness


  • Symptoms are usually present before ophthalmoscopic signs

  • Electroretinography (ERG): contact lens probe and measurement of electrical potential of the photoreceptors

  • Visual field analysis

  • Good family history, examine relatives

Treatment/ Research

  • Currently no treatment for RP

  • Low visual aids and blind registration

  • Anti-oxidants (Vitamins A+E have been tried but majority or RP patients not responsive)

  • Genetic mapping and linkage studies

  • E.g. Peripherin gene – current research to find gene therapy



  • AIDS is a multisystem disorder of opportunistic infections caused by HIV.

  • Ocular manifestations:

    • Keratitis sicca

    • Common infections: HSV/ HZO/ VZV/ CMV

    • Rarer: Candida choroiditis, Retinal toxoplasmosis

    • Neoplasms: Karposi’s sarcoma, Non-Hodgkin’s lymphoma

Herpes Simplex Keratitis: see red eye lecture

Herpes Zoster Ophthalmicus: Ophthalmic division of trigeminal nerve

CMV retinitis

  • Commonest – Occurs in 25% of AIDS patients

  • “Pizza fundus” with overlying vitritis

  • Related to high viral load or low CD4+ count

  • <50 cells/mm3 at greatest risk

Symptoms of CMV retinitis

  • May be minimal

  • Floaters and flashing lights

  • Visual field loss

  • Central visual loss (V/A)

  • Signs: progressive necrotising retinitis, retinal haemorrhage and intraretinal necrosis, hazy vitreous

CMV retinitis treatment

  • 14 day induction course: iv ganciclovir or foscarnet

  • May require lifelong treatment

  • 80-100% respond to initial therapy but 50% recur within 3 months

  • May require intravitreal injections or implants


  • Related to ocular disease or treatment

  • Blindness from retinal detachment

  • Optic nerve head involvement

  • Ganciclovir causes neutropenia

  • Foscarnet causes renal toxicity

  • Co-existence of other infections (low CD4)


Other systemic diseases

  • Remember dry eyes associated with Rheumatoid Arthritis (Sjogren’s syndrome or keratoconjunctivitis sicca)

  • Remember acute anterior uveitis associated with the seronegative arthritides (50% of patients are HLA-B27 positive and there is an association with ankylosing spondylitis)

Further reading

  • There are many other interesting associations of eye disease and general medicine - read up more in good ophthalmology textbooks (see section in the library)

    • Murray, Fielder: Pocket book of Ophthalmology (concise, short notes)

    • Batterbury: Churchill Livinstone colour guide to ophthalmology (good general text)

    • Kanski: Clinical ophthalmology (reference)

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