related to the ocular manifestation due to the systemic disease, hope this will be useful for the learner.

1. ©ECN
Ocular
Manifestations
of Systemic
Disease
Dileep Raj Gupta
Department of Ophthalmology
Devdaha medical college and teaching
hospital

2. Objectives
1. To describe the ocular signs and symptoms associated with
selected systemic diseases and their serious ocular sequelae.
2. To review the important features of diabetic retinopathy and
the current screening guidelines
3. To be familiar with the important ocular features of
hypertension, thyroid disease, sarcoidosis and inflammatory
conditions, malignancy and acquired immunodeficiency
syndrome.

3. Introduction
• "The eyes are the window to the soul."
--English proverb
• Numerous systemic diseases have ocular manifestations
• Occasionally, the eye findings may be the first indication of
underlying systemic disease leading to diagnosis

4. Differential Diagnosis
• Congenital
• Vascular
• Traumatic
• Neoplastic
•
Autoimmune
• Idiopathic
• Infectious
•
Metabolic/Endoc
rine
• Drugs/Toxins

5. Ocular Anatomy

6. Anatomy: Periocular soft tissues
niurtctrv
a
through'
Bulbar conjunctiva
Palpebral conjunctiva
Cornea
Orb*rulam ocull muscle (palpebral pari)'
Sebaceous glands
tostenor chamber
Dorsal nasal artery
Levator palpebrae superioris muscle
Orbital septum
Vlrra
Superior tarsal iMuller st muscle (smooths
Superior conjunctival fornix
Superior tarsus
Urs.il (Meibomian! glands lens
Antenor clumber
Lilia dashes!
Openings of tarsai glands
PM tk I W9III
Orbicularis ocull muscle ipalprbral pari •
Inferior coniunctmal lomix
Orbital septum
Frontal Ijone
Insertum ol levator palpebrat
superioris muscle
Orbital septum supraorbital artery and nerve
Supratrochlear arterv and nerveSuperior tarsus
Lateral palpebral ligament
and overlying raphe lacrimal vac
Interior tarsus Medial palpebral ligament
Maxilla (frontal process)Orbital septum
Intraorbital artery and nerve
cvgomtlic bone

7. Anatomy: Lacrimal System
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8. Anatomy: The Globe
Ciliary body
Choroid
Anterior chamber
Comea
PupilConjunctiva
Limbus
Posterior chamber Schlemm s canal
Zonules Leas
Sclera
Retina
us cavity
Optic disc
Fovea
Macula
Central retinal
artery and vein
Dura mater
Optic nerve

9. Anatomy: The Retina

10. • Vision
Examination
• Motility
• External
• Pupils
• Relative Afferent
pupillary defect (RAPD)
• Exam of Anterior
Segment (Slit Lamp)
• Dilated
Ophthalmoscopy
• Visual Fields

11. Hypertension
• Systolic > 130, Diastolic > 85 mmHg
• 65 million Americans
• Heart, kidneys, brain, & Eye
• May cause damage to retina, choroid, and optic nerve
• Acute & Chronic changes
• Preeclampsia

12. Hypertension
• Ocular findings
• Arteriolar narrowing & A-V
Nicking
• Cotton Wool spots
• Retinal hemorrhages
• Optic nerve swelling (edema)
• Retinal ischemia &
neovascularization
• May be associated with:
• Branch retinal artery
occlusion (BRAO)
• Branch retinal vein
occlusion (BRVO)
• Central retinal vein
occlusion (CRVO)
• Retinal artery
macroaneurysm (RAMA)

13. Hypertensive Retinopathy
Images courtesy of Redatlas.org Cotton wool spots

14. Hypertensive Retinopathy
Optic Nerve
Edema

15. Hypertensive Retinopathy
BRAO CRVO

16. Diabetes mellitus * •
• Diabetic retinopathy (DR) is leading cause of blindness in 20-
64yo in US
• Duration of DM is directly related to prevalence of retinopathy
• After 20 yrs: 99% of type 1 and 60% of type 2 will have some degree of
DR
• Pathologic changes include microvascular damage leading to
hypoxia, vascular leakage & edema, ischemia, and
neovascularization
• Prevention & Importance of systemic blood glucose, pressure,
& lipid control: DCCT, UKPDS, & ACCORD trials

17. Diabetic Retinopathy
• Classification:
• Non-Proliferative diabetic retinopathy (NPDR)
• Proliferative Diabetic Retinopathy (PDR)
• Complications Resulting in Visual Loss
• Macular edema (capillary leakage) i
• Macular ischemia (capillary occlusion)
• Sequelae from ischemia-induced neovascularization < PDR

18. Diabetic Retinopathy:
NPDR

19. Diabetic Retinopathy:
Macular Edema
Microaneurysm OR Damaged capillary
Normal capillary
Swollen retina
Normal retina

20. Diabetic Retinopathy:
PDR

21. Diabetic Retinopathy
PDR

22. Diabetic Retinopathy:
PDR
Tractional Retinal Detachment

23. Diabetic Retinopathy
Treatment
• Laser
• Pharmacologic (anti-VEGF meds)
• Surgery
fes Bye Institute
nlveqplty
Laser Pan Retinal Photocoagulation
vitrectomy instrument
vitreous is removed
fluid goes into eye
to replace vitreous
fiberoptic light
Vitrectomy
Vitrectomy Surgery

24. Diabetic Retinopathy:
Vitrectomy Surgery
Neovascularization (PDR)
4
Scar tissue, membranes, &
blood on surface of retina

25. Diabetic Retinopathy:
Screening & Prevention
* •
• Screening eye examination for all patients:
• At time of diagnosis for type 2
• Within 5 yrs of diagnosis for type 1
• Pregnancy
• Follow-up exams will be dependent on initial eye findings
• Blood glucose, Blood pressure, and Lipid optimization
• Stop smoking
• Exercise

26. Carotid Stenosis •
• Amaurosis fugax
• Hollenhorst plaque
• Retinal artery occlusion
• Ocular ischemic syndrome (& neovascular glaucoma)

27. Hollenhorst plaque

28. Carotid Stenosis:
Branch Retinal Artery Occlusion
Retinal whitening due to edema

29. Ocular Ischemic Syndrome
• *
Lk
Pain Red Eye Loss of vision
Elevated Intraocular Pressure
A Patients at risk for ischemic CV
disease, stroke, & peripheral
Vascular disease

30. Sickle Cell Disease
• Autosomal Recessive
• Genotype
• 8% Sickle cell trait (HbAS)
• 0.4% Sickle cell disease
(HbSS)
• 0.2% SC disease (HbSC)
• Sickle Thalassemia
• Systemic Complications
• Crises (painful episodes)
• Acute chest syndrome

31. Sickle Cell Disease:
Ocular Complications
•
• Frequency
• HbSC (most common) - 33%
• Sickle Thalassemia -14%
• HbSS - less frequently but have more severe
systemic complications - 3%
Pathogenesis:
• Peripheral retinal nonperfusion - ISCHEMIA =
Neovascularization Hemorrhage & Tractional
Retinal Detachment

32. ization
Sickle Cell Disease
Capillary nonperfusion in peripheral retina

33. Sickle Cell Disease:
Special Situations
• High Risk for
elevated intraocular
pressure due to sickling
of RBCs
• Require aggressive
medical & sometimes
surgical Rx to prevent
optic nerve damage
Know Sickle Cell Status for patients with Traumatic Hyphema

34. Giant Cell Arteritis
• AKA: Temporal Arteritis
Lingual artciy
Systemic granulomatous vasculitis affecting medium-
and large-sized vessels
Age > 50 yo
Symptoms
• Headache
• Scalp tenderness
• Jaw claudication
• Polymyalgia rheumatica
• Acute vision loss
Occipital —*
artery
-Temporal arten
Ophthalmic
arten
Facial arten

35. Giant Cell Arteritis
• Diagnosis:
• Clinical history
• Stat ESR &/or CRP
• Temporal artery biopsy
• Treatment:
*
0 ^ ^ ~ * ^ JMI ^
• High-dose systemic steroids (do not defer until after biopsy)

36. Giant Cell Arteritis
Dilated superficial temporal artery
Scalp Necrosis

37. Giant Cell Arteritis

39. Thyroid Eye disease
• May occur with hyper-, hypo-, or euthyroid states
• Hyperthyroidism: goiter, tremor, pretibial myxedema,
atrial fibrillation, etc
• Ocular Findings:
• Proptosis (exophthalmos)
• Lid Retraction -- Thyroid stare
• Corneal exposure (dry eye, corneal ulcer)
• Diplopia (due to eye muscle restriction)
• Optic Nerve compression (optic neuropathy) - 5%

40. Thyroid Eye Disease:
Pathophysiology
• Autoimmune process
with cross-reaction
against orbital and
periorbital soft
tissues
Enlargement of ocular rectus muscles

41. Exophthalmos:
“Thyroid Stare"

42. Thyroid Eye disease
Chemosis & Dry Eye

43. Thyroid Eye disease

44. Thyroid Eye disease:
Orbital Decompression
(For TED-related Optic Neuropathy)

45. Thyroid Eye disease:
Management * •
• Treatment Considerations:
• Artificial tears & lubrication
• Systemic steroids & external beam radiation (if vision
threatening)
• Surgery:
• Orbital decompression
• Eye muscle surgery
• Eyelid Surgery
• Stop Smoking

46. HIV & AIDS
• Eyelids: Kaposi sarcoma,
molluscum contagiosum,
Herpes zoster ophthalmicus
• Orbit: Cellulitis, B-cell
lymphoma
• Cornea: Keratitis
(microsporidium, HSV,
HZV)
• Keratoconjunctivitis sicca
(severe dry eye)
• Anterior uveitis
• HIV retinopathy
• Retinitis (CMV, VZV,
toxoplasmosis)
• Choroiditis (pneumocystis,
toxoplamosis)
• B-cell intraocular lymphoma

47. Kaposi Sarcoma
• Purplish red to bright red highly vascular lesions with
surrounding telangiectatic vessels
• Associated with Human Herpes Virus-8 (HHV-8)
• 20-24% of AIDS-related Kaposi sarcoma will involve eye
• Eyelid & Conjunctiva
• Mostly local mass effects - pain, poor eyelid closure, etc
• Treatment: chemotherapy, surgical (if large to debulk)

48. Kaposi Sarcoma
Photos courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute

49. • Typically multiple lesions in
HIV or AIDS

50. HIV/AIDS:
Herpes Zoster
Hutchinson’s
sign

51. AIDS:
CMV Retinitis
* •
• Most common intraocular infection with AIDS
• Much reduced incidence since HAART (50% to 10% of pts)
• CD4 count typically < 50 cells/mm3
• Retinal necrosis, exudation, & hemorrhage
• Treatment:
• IV ganciclovir/foscarnet
• Intravitreal ganciclovir/foscarnet; Ganciclovir
intravitreal implant

52. AIDS:
CMV Retinitis
CD4 < 50

53. HIV/AIDS:
Toxoplasmosis Retinitis

54. = Tertiary Syphilis Need
LP
Rx with IV Penicilin G

55. Tuberculosis
Granulomas
Uveitis
Choroidal granulomas
Periphlebitis
Choroidal Tubercules

56. Septicemia & Endogenous
Endophthalmitis
• Hematologic seeding of the eye
with infection
• Gram-positive, gram-negative,
fungal etiologies
• Candida is most common causative
organism
• Immunocompromised or
immunosuppressed patients
• Bilateral in 25%
• Clincial scenarios: Endocarditis,
pneumonia, indwelling catheter
(fungal), following surgery (cardiac,
pulmonary, urologic)
• Treatment: IV Anti-bacterial/fungal
• Adjunctive: +/- intravitreal antibiotics,
Vitrectomy surgery
• Chronic diseases (DM, Renal failure) &
indwelling lines or invasive
procedures, & intravenous
hyperalimentation •
• IV Drug Use

57. Septicemia & Endogenous
Endophthalmitis
Pneumonia
Medscape® www.medscape.com
Hypopyon
Source: Inled Med © 2004 Cliggott Publishing. Division ol SCP Communications

58. Septicemia & Endogenous
Endophthalmitis
Vitreous Haze & Debris
(Obscures view of retina)
Fungal Endophthalmitis

59. Ankylosing spondylitis
• Spondylarthropathy of the axial
skeleton
• Typically affects males (4:1)
• 90% are HLA-B27 (+)
p ;
Normal Advanced
posture ankylosing
i* *Tl
spondylitis
V
(
f
• Presents in early adulthood (15-35 yo) with pain & stiffness
in lower back
• Limitation of spinal flexion
• Juxta-articular osteoporosis & fusion of sacro-iliac joints
• "Bamboo spine"

60. Ankylosing spondylitis
• Ophthalmic features:
• Anterior uveitis in 30-40%
• Symptoms
• Photophobia
• Redness
• Decreased vision •
• Treatment:
• Topical corticosteroids
• Cylcoplegia

61. Ankylosing spondylitis

62. Behcet's Disease
• Vasculitis leading to chronic inflammation & ulceration
• Oral aphthaous ulcers
• Genital ulcers
• Skin lesions (e.g. erythema nodosum)
• Eye inflammation (iritis, retinal vasculitis)

64. Inflammatory Bowel Disease (IBD):
Crohn's Disease & Ulcerative
Colitis * •
• Ulcerative colitis: relapsing, non-transmural, restricted to
colon
• Crohn's disease: relapsing, transmural, affects entire GI
tract
• Ocular complications in
10%
• Uveitis• Episcleritis
• Scleritis
Women at higher risk
Associated with HLA-B27

65. Sarcoidosis
• Focal noncaseating granulomas
• AA females, 20-40 yo
• Elevated Calcium, ACE, abnormal CXR
• Lacrimal gland granulomas
• Anterior uveitis
Hilar Lymphadenopathy
• Retinal inflammation
• Ocular complications: glaucoma, cataract

66. Sarcoidosis
©ECN
Lacrimal Gland Granuloma

67. Sarcoidosis

68. Sarcoidosis
Posterior Synechiae of the iris

70. Sarcoidosis
Perivascular Inflammation

71. Rheumatoid Arthritis
• 25% may have ocular findings
• Dry eyes (15-25%)
• Episcleritis
ifl' T
• ScleritisV h _ r
- . v . -1X ^B ^B ■
1 T^t * -fit » 1 •' ►“* ■ V, j * «H 2
• Corneal ulcers
r
i' „ ? # w»*• uveitis

72. Rheumatoid Arthritis
Peripheral Ulcerative Keratitis

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74. Multiple Sclerosis:
Optic Neuritis
50% of patients with MS will develop Optic Neuritis 20-30%
of time will be presenting sign for MS

75. Metastatic Disease
• Most common intraocular malignancy in adults
• May be asymptomatic
• May produce decreased or distorted vision
• Most common primary: Lung, Breast
• 10% have unknown primary
• No prior history of Cancer in 25%

76. Metastatic Lung Cancer

77. Metastatic Breast Cancer
Elevated Amelanotic Mass in Macula S/p ChemoRx

78. Myasthenia gravis
• Autoimmune neuromuscular disorder leading to fluctuating
muscle weakness & fatiguability
• Circulating antibodies block Ach receptors at post-synaptic
NM junction, inhibiting stimulative effect of neurotransmitter
Ach
• Ptosis, double vision, problems chewing, talking, and
swallowing
• Diagnosis: Tensilon test, single-muscle fiber EMG
• Treatment: Acetylcholinesterase inhibitor (Mestinon)

79. Myasthenia gravis

80. Neurofibromatosis-1
Autosomal
Dominant
Chromosome 17Diagnostic Criteria
• Cafe au lait spots
• Intertrigenous freckle
• Neurofibroma
• Optic nerve glioma
• Lisch nodules
• Osseous leasions
• Family history in 1st
degree relative

81. Neurofibromatosis-1

82. Neurofibromatosis-1
S-Shaped Eyelid Neurofibroma

83. Neurofibromatosis-1
20% with NF-1
will have Optic
Nerve glioma
50% of pts with
optic nerve glioma
have NF-1
Optic Nerve Glioma

84. Sturge-Weber Syndrome
• Sporadically inherited phakomatoses
• Glaucoma
• Dilated & tortuous episcleral vessels
• Seizures
• CNS angiomas (Leptomeningeal hemangioma)
• calcification

85. Sturge-Weber Syndrome
Nevus flammeus (Port Wine Stain)

86. Sturge-Weber Syndrome:
Choroidal Hemangioma

87. Systemic Medications
• Benign ocular conditions
• Amiodarone - whorl keratopathy
• Toxic Retinopathies
• Thioridazine, chloroquine, hydroxychloroquine, tamoxifen
• Toxic Optic Neuropathies
• Ethambutol, isoniazid

88. Hydroxychloroquine: Ophthalmic
Screening
• Used for rheumatoid arthritis, SLE, etc
• Ocular toxicity rare with usual dose 200 mg bid (5-
7mg/kg/day)
• Toxicity related to cumulative dose (>460 g) & duration of use
• Ocular findings: bulls-eye retinopathy
• Recommended screening:
• Baseline exam & Central VF testing
• Annual examination & repeat central VF for pts using medicine > 5
yrs

89. Plaquenil toxicity:
Bull's Eye Maculopathy

90. Thank You for your Attention
???Any Questions???