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«Ocular Manifestations of Systemic Disease Jacob J. Yunker, MD Diseases and Surgery of the Retina, Macula & Vitreous Assistant Professor, Department ...»



of Systemic


Jacob J. Yunker, MD

Diseases and Surgery of the Retina, Macula &


Assistant Professor, Department of Ophthalmology

University of Kentucky College of Medicine


1. To describe the ocular signs and symptoms associated

with selected systemic diseases and their serious ocular


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.

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 Differential Diagnosis Congenital Idiopathic Vascular Infectious Traumatic Metabolic/Endoc rine Neoplastic Drugs/Toxins Autoimmune Ocular Anatomy Anatomy: Periocular soft tissues Anatomy: Lacrimal System Anatomy: The Globe Anatomy: The Retina The macula = central vision Examination  Vision  Motility  External  Exam of Anterior Segment (Slit Lamp)  Pupils  Dilated  Relative Afferent Ophthalmoscopy pupillary defect (RAPD)  Visual Fields 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 Hypertension  Ocular findings  May be associated with:

 Arteriolar narrowing & A-V  Branch retinal artery Nicking occlusion (BRAO)   Branch retinal vein Cotton Wool spots occlusion (BRVO)  Retinal hemorrhages  Central retinal vein  Optic nerve swelling occlusion (CRVO) (edema)  Retinal artery  Retinal ischemia & macroaneurysm (RAMA) neovascularization Hypertensive Retinopathy Cotton wool spots Images courtesy of Redatlas.org Hypertensive Retinopathy Optic Nerve Edema Hypertensive Retinopathy

–  –  –

 Diabetic retinopathy (DR) is leading cause of blindness in 20yo 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 Diabetic Retinopathy  Classification:

 Non-Proliferative diabetic retinopathy (NPDR)  Proliferative Diabetic Retinopathy (PDR)

–  –  –

 Sequelae from ischemia-induced neovascularization PDR

Diabetic Retinopathy:


Diabetic Retinopathy:

Macular Edema

Diabetic Retinopathy:


–  –  –

Neovascularization (PDR)

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

–  –  –

 Amaurosis fugax  Hollenhorst plaque  Retinal artery occlusion  Ocular ischemic syndrome (& neovascular glaucoma) Hollenhorst plaque

Carotid Stenosis:

Branch Retinal Artery Occlusion

–  –  –

 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

Sickle Cell Disease:

Ocular Complications  Frequency  HbSC (most common) – 33%  Sickle Thalassemia – 14%  HbSS – less frequently but have more severe systemic complications – 3%

–  –  –

 Require aggressive medical & sometimes surgical Rx to prevent optic nerve damage Know Sickle Cell Status for patients with Traumatic Hyphema Giant Cell Arteritis  AKA: Temporal Arteritis  Systemic granulomatous vasculitis affecting medium- and large-sized vessels  Age 50 yo  Symptoms  Headache  Scalp tenderness  Jaw claudication  Polymyalgia rheumatica  Acute vision loss Giant Cell Arteritis  Diagnosis:

 Clinical history  Stat ESR &/or CRP  Temporal artery biopsy  Treatment:

 High-dose systemic steroids (do not defer until after biopsy) Giant Cell Arteritis Dilated superficial temporal artery

–  –  –

Superficial Temporal artery 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%

Thyroid Eye Disease:

Pathophysiology  Autoimmune process with cross-reaction against orbital and periorbital soft tissues Enlargement of ocular rectus muscles Thyroid Eye disease


“Thyroid Stare” Thyroid Eye disease

–  –  –

 CT scan orbits or Orbital Ultrasound  Look for enlargement of eye muscles  Restrictive myopathy = Double Vision

Thyroid Eye disease:

Orbital Decompression (For TED-related Optic Neuropathy)

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

–  –  –

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


Molluscum contagiosum

–  –  –

 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


CMV Retinitis CD4 50


Toxoplasmosis Retinitis

–  –  –

Fungal Endophthalmitis Ankylosing spondylitis  Spondylarthropathy of the axial skeleton  Typically affects males (4:1)  90% are HLA-B27 (+)  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” Ankylosing spondylitis  Ophthalmic features:

 Anterior uveitis in 30-40%  Symptoms  Photophobia  Redness  Decreased vision  Treatment:

 Topical corticosteroids  Cylcoplegia

–  –  –

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

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

–  –  –

50% of patients with MS will develop Optic Neuritis 20-30% of time will be presenting sign for MS 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% Metastatic Lung Cancer Metastatic Breast Cancer

–  –  –

 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) Myasthenia gravis

–  –  –

Fatiguability Neurofibromatosis-1  Autosomal Dominant  Chromosome 17  Diagnostic Criteria  Café au lait spots  Intertrigenous freckle  Neurofibroma  Optic nerve glioma  Lisch nodules  Osseous leasions  Family history in 1st degree relative Neurofibromatosis-1 Seen in 90% of cases Neurofibromatosis-1

–  –  –

 Sporadically inherited phakomatoses  Glaucoma  Dilated & tortuous episcleral vessels  Seizures  CNS angiomas (Leptomeningeal hemangioma)  calcification Sturge-Weber Syndrome Nevus flammeus (Port Wine Stain)

Sturge-Weber Syndrome:

Choroidal Hemangioma Systemic Medications  Benign ocular conditions  Amiodarone – whorl keratopathy  Toxic Retinopathies  Thioridazine, chloroquine, hydroxychloroquine, tamoxifen  Toxic Optic Neuropathies  Ethambutol, isoniazid 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

Plaquenil toxicity:

Bull’s Eye Maculopathy Thank You for your Attention

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