WCS32 Ocular Manifestations Of Systemic Disease

Question 1

Systems related to eyes

Answer 1

1. Endocrinology
2. Rheumatology
3. CVS disease
4. Skin and Paediatric conditions
5. Drug-related

Question 2

Diabetes Mellitus and Eyes

Answer 2

1. Diabetic retinopathy
   - **Non-proliferative (NPDR) (Earlier stage)
   - **Proliferative (PDR) (Later stage)
   —> may NOT affect central vision
2. Diabetic maculopathy
   —> affect central vision

Question 3

Symptoms of Diabetic retinopathy

Answer 3

記: MCV, HDI

1. ***Microaneurysm
   - Hallmark of diabetic retinopathy
   - Earliest sign
2. Retinal haemorrhage (***Dot-and-blot, flame-shaped)
   - usually visually insignificant
3. ***Hard exudates
   - accumulation of lipoproteins leaked from vessels
4. ***Cotton wool spots
   - focal areas of infarction of retinal nerve fibre
5. ***Venous beading
   - increasing ischaemia
6. Intra-retinal microvascular abnormalities (IRMA)
   - anastomosis between arterioles and venules
   - vs Neurovascularisation (network-like) (IRMA: much smaller)

Question 4

***Pathophysiology of Diabetic retinopathy

Answer 4

Retinal microangiopathy (e.g. Microaneurysm, Retinal haemorrhage) —>

1. ***Breakdown of Blood-Retinal Barrier —> Macula edema
   - Hard exudates
2. ***Retinal ischaemia —> Vasoproliferative substances (e.g. VEGF) (Neovascularistion) —> Macula edema
   - Cotton wool spots
   - Venous beading
   - IRMA

Question 5

***Non-proliferative Diabetic Retinopathy (NPDR)

Answer 5

Mild:
- ***>= 1 Microaneurysm

Moderate:

• ***Multiple microaneurysm
• Dot-and-blot haemorrhages
• Venous beading
• +/- Cotton wool spots

Severe (***4-2-1 rule):

• Diffuse haemorrhage + Microaneurysms in ***4 Quadrants
• Venous beading in 2Q
• IRMA in >=1Q
• > 50% progress to PDR

Question 6

***Proliferative Diabetic Retinopathy (PDR)

Answer 6

1. ***Retinal neovascularisation
2. ***Vitreous haemorrhage
3. Pre-retinal fibrosis (***regression of neovascularisation)
4. Rubeosis iridis (NVI)
   - impending Neovascular glaucoma

Question 7

***Diabetic maculopathy

Answer 7

Symptoms

1. Multiple exudate / cystic space
2. Dull macula
3. Macular edema —> Loss of depression at fovea
4. Loss of central vision

Pathophysiology:
1. Breakdown of Blood-retinal barrier
2. Vasoproliferative substances (VEGF)
Both —> Macula edema

Question 8

Complications of Diabetic retinopathy / maculopathy

Answer 8

1. ***Cataract (usually cortical)
2. ***Neovascular glaucoma (newly formed blood vessels —> fibrosis —> closes the angle)
3. ***Tractional retinal detachment

Question 9

Treatment of Diabetic Retinopathy / Maculopathy

Answer 9

Mild / Moderate NPDR
- ***Glycaemic control (diet, medication)

Severe NPDR / PDR
- ***Panretinal laser photocoagulation (PRP)
—> killing of retinal tissue to prevent progression + preserve macula
—> impair peripheral vision + night vision

Clinically significant macula edema (CSME)

• Intravitreal ***anti-VEGF (Ranibizumab / Aflibercept)
• Intravitreal ***steroid (Triamcinolone / Ozurdex)
• ***Focal / grid laser if no macula ischaemia —> obliterate leaking microaneurysm + stimulate retinal pigmented epithelium to absorb more water in cystic space

Question 10

Thyroid eye disease (TED) / Graves’ ophthalmopathy / Orbitopathy (GO)

Answer 10

• Typically associated with Graves’ hyperthyroidism
• Also occur with hypothyroidism / euthyroid individuals
• Immune-mediated

Orbital signs:

1. ***Exophthalmos / Proptosis
2. ***Limited EOM / Squint

Eyelid / Ocular signs:

1. Lid retraction
2. Lid lag
3. Lagophthalmos (incomplete closure of the eyelids)
4. Lid puffiness / Erythema
5. Conjunctival injection / Caruncle inflammation / Chemosis (conjunctival swelling)

Question 11

Ocular complications in TED

Answer 11

1. ***Compressive optic neuropathy
2. ***Exposure keratopathy —> cannot close eyes
3. Increased IOP / Glaucoma

Question 12

CT Orbit in TED

Answer 12

1. ***Tendon sparing muscle enlargement (Pathognomonic for TED)
2. Look for ***apical crowding (Compression of the optic nerve at the apex of the orbit by enlarged extraocular muscles —> looking for complication)

Question 13

Phases in TED

Answer 13

1. Active phase:
   - Inflammatory (6-18 months)
2. Quiescence phase:
   - Post-inflammatory

Question 14

***Activity and Severity of TED

Answer 14

Activity:
Clinical Activity Score (CAS)
Active: CAS >=3
1. Spontaneous retrobulbar pain
2. Pain on eye movements
3. Eyelid erythema
4. Conjunctival injection
5. Chemosis
6. Swelling of the caruncle
7. Eyelid edema / fullness

Severity (**Exophthalmos, **Lid retraction):

1. Mild
   - minor lid retraction (<3mm)
   - transient / no diplopia
   - corneal exposure responsive to lubricants
2. Moderate to Severe
   - lid retraction (>=2mm)
   - moderate / severe soft tissue involvement
   - exophthalmos >=3mm above normal for race + gender
   - inconstant / constant diplopia
3. Sight threatening
   - Dysthyroid optic neuropathy (DON)
   - Corneal breakdown (Exposure keratopathy)

Question 15

Management of TED

Answer 15

Mild:

• ***Quit smoking
• Normalise thyroid function
• Symptomatic treatment (e.g. lubricants for dry eyes)

Moderate to Severe:

• Active —> Immunosuppression with ***Steroid (weekly IV infusion Methylprednisolone 12 weeks)
• Inactive —> Surgeries (***Orbital —> Squint —> Lid)

Sight-threatening:
- Immediate intervention needed
—> DON: IV steroid + **Orbital decompression (thinning of **medial wall + **floor (X Lateral wall + Superior roof))
—> **Exposure keratopathy: Meds + Tape +/- Decompression

Question 16

Teprotumumab

Answer 16

Anti-IGF1 Ab

• Insulin-like growth factor 1 receptor
• Rapidly effective in decreasing disease activity

Question 17

Rheumatology and Eyes

Answer 17

Collagen + Vessels

Autoimmune diseases with ophthalmic manifestations

1. Seronegative spondyloarthropathies (***HLA-B27, ANA and RF -ve)
   - Ankylosing spondylitis
   - IBD-associated
2. RA
3. SLE
4. Sjögren’s syndrome
5. Sarcoidosis

Question 18

Ocular manifestations of Rheumatology disease

Answer 18

1. ***Uveitis
2. ***Peripheral Ulcerative Keratitis (PUK)
3. ***Keratoconjunctivitis sicca (Sjögren’s)
4. ***Episcleritis / Scleritis
5. Retinal vein occlusion
6. ***Ischaemic optic neuropathy

Question 19

Anterior uveitis vs Panuveitis

Answer 19

Anterior uveitis:
- Mostly commonly isolated + idiopathic
- Commonest association is **Seronegative spondyloarthropathies
—> esp. with **HLA-B27 allele
—> Ankylosing spondylitis, Psoriatic arthritis, IBD associated, JIA
- Others: RA, SLE, Sarcoidosis

Panuveitis:

• Anterior uveitis + ***Posterior segment inflammation (Chorioretinitis, Vitritis, Retinal vasculitis)
• Much less common
• Usually associated with ***Behcet disease

Question 20

Signs of Anterior Uveitis

Answer 20

1. Ciliary flush
2. Keratic precipitates (KP) —> inflammatory cellular deposit seen on corneal endothelium
3. Anterior chamber cells
4. Posterior synechiae (PS) —> Iris stick on the lens
5. Hypopyon —> Exudate (death inflammatory cells) in lower part of eyes

Question 21

Uveitis treatment

Answer 21

Anterior uveitis:

1. ***Topical steroid
   - intensive initially then taper gradually
2. ***Topical cycloplegics (e.g. homatropine, atropine)
   - relieve pain due to ciliary spasm
   - prevent posterior synechiae
3. If steroid resistant / dependent
   - AC tapping to rule out infection (HSV, VZV, CMV, TB)
   - Subtenon steroid for unilateral disease (Triamcinolone)

Panuveitis / Posterior uveitis
1. Treat underlying condition

2. ***Systemic steroid +/- immunomodulator
3. ***Intravitreal steroid (Triamcinolone, Ozurdex)
   - more for unilateral cases
4. Biologics: ***TNF inhibitors (Infliximab, Adalimumab)

Question 22

Peripheral Ulcerative Keratitis (PUK)

Answer 22

Signs

1. Crescent shape ulcer
2. Active ulcer on peripheral scar
3. Corneal thinning
4. Perforation

• Mainly associated with ***RA
  —> others: collagen vascular disease (SLE), IBD
• Mooren’s ulcer if isolated

Treatment:

1. Systemic (Inflammation control)
   - Systemic steroid (Prednisolone +/- IV Methylprednisolone)
   - Immunomodulators (MTX, Azathioprine, Cyclosporin A, Cyclophosphamide)
   - Biologics (Infliximab, Rituximab)
2. Local (Damage control)
   - Preservative free lubricants
   - Topical antibiotics
   - Conjunctival recession
3. Prevent perforation
   - protect with eye shield
   - corneal melting —> avoid topical steroid
4. Small / impending perforation
   - Cyanoacrylate glue + Bandage contact lens (BCL)
5. Larger perforation
   - Corneal patch graft

Question 23

CVS disease and Eyes

Answer 23

Hypertensive retinopathy
Grade 1: Barely detectable arterial narrowing
Grade 2: Obvious **arterial narrowing with focal irregularities
Grade 3: Grade 2 + **Retinal haemorrhage + Exudates + CWS + Retinal edema
Grade 4: Grade 3 + ***Papilloedema

Question 24

Skin + Paediatric conditions and Eyes

Answer 24

Herpes Zoster Ophthalmicus

• reactivation of latent VZV in Trigeminal ganglia (V1, V2)
• ***Hutchinson’s sign (Nasociliary nerve affected —> more likely to have Intraocular inflammation)

Ocular involvements:

• Conjunctivitis
• ***Keratitis (Microdendritic lesions) (Simplex virus: Large dendritic lesions)
• ***Anterior uveitis
• Episcleritis
• Scleritis
• Trabeculitis (↑ IOP)
• Retinitis
• Retinal vasculitis
• Choroiditis
• Optic neuritis

Question 25

Management and Sequelae of Herpes Zoster Ophthalmicus

Answer 25

Management: 1. Airborne precaution until lesions crusted 2. Oral ***Aciclovir 800mg 5x/day for 7-10 days 3. +/- Ointment Aciclovir 5x/day 4. Treatment for ocular complications Potential sequalae: - Post-herpetic neuralgia - Skin scarring - Sequalae of ocular complications

Question 26

Marfan syndrome

Answer 26

- Autosomal dominant trait - Defective ***FBN1 gene at chromosome 15 —> Encoding fibrillin-1 * **Ectopia lentis (Lens subluxation / dislocation) - Idiopathic - Ocular causes: trauma, pseudoexfoliation syndrome - Systemic causes: Marfan syndrome (most common, superotemporal subluxation), Homocystinuria (2nd most common, inferonasal subluxation)

Question 27

Neurocutaneous Syndrome (aka Phakomatoses)

Answer 27

1. Sturge-Weber syndrome | 2. Neurofibromatosis Type 1

Question 28

1. Sturge-Weber syndrome

Answer 28

Vascular malformation involving Leptomeninges + Facial skin Neuro: ***Leptomeningeal angioma - Developmental delay / Intellectual disability - Seizures / Epilepsy Cutaneous: ***Port-wine stain - aka Nevus flammeus - Typically V1, V2 distribution Ophthalmic problems: - Glaucoma - Diffuse choroidal hemangioma

Question 29

2. Neurofibromatosis Type 1

Answer 29

- aka ***Von Recklinghausen’s Disease - AD inheritance with high penetrance - Mutation / Deletion of ***NF1 gene at chromosome 7q —> encode neurofibromin Diagnostic criteria: 1. ***Plexiform neurofibroma 2. ***Optic glioma 3. >=1 Lisch nodules 4. ***Sphenoid dysplasia (pulsatile proptosis)

Question 30

Drug-related ophthalmic conditions

Answer 30

1. Bull’s eye maculopathy - ***Chloroquine >> Hydroxychloroquine - Risk correlates to daily dose, duration of use and total accumulative dose - Other risk factors: Age, liver, renal impairment, obesity 2. Vortex keratopathy - aka Cornea verticillata - Whorl-like pattern of golden brown / gray deposits in the inferior - ***Amiodarone - Other drugs: Chloroquine / Hydroxychloroquine, Indomethacin, Phenothiazine 3. Eyelid hypertrichosis and Trichomegaly - Systemic medication: Eriotinib —> Prominent Trichomegaly with curling of lashes - Topical medication: Prostaglandin analogs (Bimatoprost, Latanoprost) —> Hypertrichosis > Trichomegaly, much less lashes curling - Hirsutism: Cyclosporine, Tacrolimus, Phenytoin, Interferon-α2b

Question 31

***Systemic steroid + Topical steroid

Answer 31

Systemic steroid: 1. Central Serous Chorioretinopathy (CSC) 2. Cataract (Posterior subcapsular) Topical steroid: 1. Partial ptosis - mild ptosis - Muller muscle atrophy 2. Increased IOP / Glaucoma - also in systemic steroid use 3. Cataract - Posterior subcapsular type - fast visual deterioration

Question 32

***Important points

Answer 32

1. DM: Retinopathy vs Maculopathy 2. Thyroid eye disease: Activity vs Severity 3. Herpes Zoster Ophthalmicus 4. Uveitis and associated autoimmune disease 5. Steroid side effects