Eye In Systemic Diseases 10/14/2019 10:51 AM Eye In Systemic Diseases Prepared By: Moath A. Nassar © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

10/14/2019 10:51 AM Systemic Diseases ? Systemic diseases are diseases that involve many organs or the whole body. Many of these diseases also affect the eyes. In fact, an eye exam sometimes leads to the first diagnosis of a systemic disease Why is the eye so important in systemic disease? The eye is composed of many different types of tissues. This unique feature makes the eye susceptible to a wide variety of diseases as well as provides insights into many body systems.  © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

Systemic diseases to be discussed : 10/14/2019 10:51 AM Systemic diseases to be discussed : Collagen vascular disease Spondyloarthropathies Sarcoidosis Systemic vasculitis Blood disorders Demyelinating disorders Hypertention and vascular diseases Thyroid disorders General signs & symptoms Diagnostic tests General management Ocular involvement Signs & symptoms Treatment and prognosis © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

1.Collagen vascular disease   problems with the immune system affect collagen wide category of diseases Symptoms of collagen vascular disease vary from disease to disease, but may include: Back pain Chest pain and shortness of breath Fatigue and weakness Fever Painful, swollen joints Rashes Diagnosis Hx & physical examination, Blood tests can check level of autoantibodies, RF, urinalysis ,LFT , KFT , ESR, C- XR Treatment Some may go into remission spontaneously Depends on the extent of the disease Steroids or anti-inflammatory medications to ease discomfort In advanced cases, immunosuppressant drugs may help  

10/14/2019 10:51 AM a. Behçet's disease Recurrent multisystemic disease presented during third to fourh decade Major diagnostic criteria : Recurrent oral aphthous stomatitis Skin lesions ( erythema nodosum,…) Recurrent genital ulceration Uveitis : both anterior and posterior Minor diagnostic criteria Arthritis , epididymitis, intestinal ulceration , neurological and vascular complications Four major criteria simultaneously or at different times is diagnostic © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

Hypopyon which can be seen in anterior uveitis in a patient with Behcet's disease.  Acute anterior uveitis generally responds to corticosteroid eye drops. Inflammation involving the back of the eye requires treatment that is more aggressive with corticosteroids given by injection and/or pill (systemic therapy). may lead to blindness in 20% of those affected 

b. Sjögren's syndrome Ophthalmic features Autoimmune inflammation and destruction of lacrimal and salivary glands Primary or secondary F>M Presented in adult life with gritteness( sandiness) of eyes and dryness of the mouth Signs Large salivary glands with diminished salivary flow Dry nasal passages Raynaud’s phenomenon Diagnosed by serum autoantibodies and biopsies Ophthalmic features Common :Keratoconjunctivitis sicca Rare : adie pupil Treatment If mild tear substitutes would help Avoiding low humidity environment Occluding the punctum in severe cases

keratoconjunctivitis sicca 10/14/2019 10:51 AM keratoconjunctivitis sicca Complete cure could never be achieved but fowolloing a strict treatment guidelines may improve the outcome © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

c. Systemic Lupus Erythematosus 10/14/2019 10:51 AM c. Systemic Lupus Erythematosus Autoimmune non-organ specific connective tissue disease F>M Presented during third to fifth decade with fatiguabilty without specific organ involvement Signs Mucocutaneous, musculoskeletal, renal, cardiovascular, pulmonary, haemopoitic, reticuloendothelial, neurological. Diagnosis: ESR is raised, C- ractive protein is normal, serology. Treated by steriods and cytotoxic agents Ophthalmic complications Common: Madarosis and keratoconjunctivitis sicca Uncommon: peripheral ulcerative keratitis Rare: scleritis, retinal vasculitis and optic neuropathy © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

Discoid lesions is the cause in this case 10/14/2019 10:51 AM Madarosis is the absence or loss of the eyelashes (and sometimes the eyebrows) Discoid lesions is the cause in this case © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

d. Rheumatoid arthritis 10/14/2019 10:51 AM d. Rheumatoid arthritis Autoimmune systemic disease characterized by symmetrical, destructive, deformating, inflammatory, polyarthropathy F>m Presented during the fourth decade and occasionally during the childhood Signs Arthritis ( symmetrical involvement of small joints of hands and feet, ulnar deviation ,…) Skin ( raynaud’s phenomenon, vasculitis , …) Treated by NSAIDs, cytotoxic drugs ,… Ophthalmic features Common: keratoconjunctivitis sicca ( secondary ) Uncommon: scleritis and peripheral ulcerative keratitis Rare: acquired superior oblique tendon sheath syndrome © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

Scleromalacia ; potential perforation 10/14/2019 10:51 AM Scleromalacia ; potential perforation tumour necrosis factor (TNF) blockers (infliximab) are effective therapeutic agents in ocular complications of rheumatoid arthritis © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

e. Systemic scleroderma Chronic connective tissue disease affecting the skin and internal organs F>M May be limited , diffuse and overlapping with other autoimmune diseases Presented in the fourth to sixth decade with raynaud phenomenon Signs: Skin: tightening and thickening on hands , feet , face and trunk. Subcutaneous fibrosis, typical facial appearance( fixed expression, restrictive movements of lips and “ beaking of nose) Organs: esophageal dysmotility, heart , lung and kidney disease, mild arthritis Diagnosis: serology Treatment: Immunosuppressive agents, Antifibrotic agents, Anti-infammatory agents,….. Ophthalmic features Common: eyelid tightening and telangectasia Uncommon: keratoconjunctivitis sicca

Skin tightening on the face ( including the eyelids) Telangiectasia

2.Spondyloarthropathies Group of inflammatory joint diseases including: Ankylosing spondylitis Reactive arthritis( reiter’s syndrome ) Psoriatic arthropathy Arthritis associated with inflammatory bowel disease(enteropathic spondylitis ) Isolated acute anterior uveitis An association with HLA –B27 occurs in all of them but in particularly strong for ankylosing sponndylitis ( > 95%) and reiter’s disease ( 90 %) They share common clinical features: Asymmetrical inflammatory oligoarthritis, Sacroiliitis and inflammatory spondylitis Diagnosis: Hx , exam ,radiographs, HLA B- 27, serology Ophthalmic features: Thay all cause acute anterior uveitis conjunctivitis, keratitis, keratoconjunctivitis sicca, scleritis

Recurrent Iritis caused Synechiae(adhesions between the lens and iris) in ankylosing spondylitis

corneal infiltrate is Uncommon feature Conjunctivitis (figure) is a common ophthalmic feature of Reiter's syndrome along with acute anterior uveitis corneal infiltrate is Uncommon feature Conjunctivitis is not very painful, does not affect vision, and is not serious and goes without treatment

Scleritis in Crohn disease If mild, could be treated by NSAIDs but if severe , systemic steriods may be introduced Also we may have conjunctivitis , peripheral corneal infiltrate & retinal periphlebitis in Crohn disease

3.Sarcoidosis Multi- systemic granulumatous inflammatory disorder Presentaion: Acute onset sarcoidosis typically occurs during the third decade Insidious onset sarcoidosis occurs during the fifth decade Signs Pulmonary : in 90 % of patients, ranges from asymptomatic bilateral hilar lymphadenopathy to progressive pulmonary fibrosis and bronchectasis Skin : erythema nodosum, granuloma Neurological : cranial nerve palsies ( particularly facial) , intra cranial granuloma Diagnosis: Chest radiographs Biopsy : Lungs , gives the greatest yield Conjunctiva , positive in about 70 % Lacrimal glands, positve in 25 % of unenlarged and 75 % of enlarged Calcium assay

Treatment options include NSAIDs steroids and low dose cytotoxic agents Ophthalmic features Common : conjunctival granulomas, anterior uveitis, posterior uveitis and retinal periphlebitis Uncommon : keratoconjunctivitis sicca and intermediate uveitis Rare: fundus granulomas, retinal and disc neovascularization, and papilloedema Mild symptoms are treated by topical steroids and cycloplegics. Systemic steroids are indicated in cases not responding to topical steroids

Anterior segment granulomatous involvement in a case of ocular sarcoidosis

Conjunctival granulomas in ocular sarcoidosis

A: Scattered peripheral multifocal lesions characteristic of ocular sarcoidosis.  B: The macula of the same patient demonstrating a choroidal neovascular membrane.

4.Systemic vasculitis The systemic vasculitides are characterized by inflammation of blood vessel walls Vessels of any type, in any organ can be affected, classified based on affected vessel size (large, medium, and small) Signs and symptoms Nonspecific complaints Those should raise a strong suspicion: Mononeuritis multiplex, palpaple purpura, pulmonary renal syndrome Diagniosis : a compatible clinical presentation supported by specific laboratory or imaging tests and confirmatory histology Glucocorticoids are the primary treatment for many forms of vasculitis , Additional immunosuppressive agents are sometimes required

a. Giant cell arteritis A granulumatous necrotizing arteritis with predilection for large and medium size arteries , particularly the superficial temporal , ophthalmic, posterior ciliary and proximal vertebral Presented during the seventh to eighth decade with the following: Scalp tenderness, headach, jaw claudication (pthognomonic) , polymyalgia rheumatica , non specifc symptoms, blindness ( sudden with minimal systemic upset), superficial temporal arteritis ( thick , tender, inlammed, and nodular arteries which can’t be flattened against the skull), the pulsation later ceases which strongly suggestive of GCA Diagnostic tests High ESR , CRP Temporal artery biopsy should be performed Treatment : by administration of systemic steriods

Ophthalmic features Common: anterior ischemic optic neuropathy Uncommon: cotton wool spots, central retinal artery occlusion , ocular motor nerve palsy ( commonly a pupil sparing third nerve palsy ) Rare: ocular ischemic syndrome Typical findings of a patient with arteritic ischemic optic neuropathy. Note the pallid disk edema, associated hemorrhages, and adjacent cotton wool spot Treatment for arteritic ischemic optic neuropathy is CORTICOSTEROID MEDICATIONS

b. Polyarteritis nodosa Idoipathic , potentially lethal , collagen vascular disease affecting medium sized and small arteries Presented during the sixth decade Signs Skin: purpura and easy bruising , gangrene Muscles: weakness and tenderness Complications Renal involvement and hypertension Coronary arteritis GI bleeding Stroke or multifocal neuropathy Diagnosis: skin biopsy Treatment: systemic steriods and immunosuppressive agents

Ophthalmic features Common: peripheral ulcerative keratitis and scleritis Rare: orbital pseudo-tumour and occlusive retinal periarteritis Peripheral ulcerative keratitis presents with a crescent shaped destructive lesion of the juxtalimbal corneal stroma

c. Wegener’s granulomatosis Idiopathic , multisystem, granulomatous disorder characterized by generalized small-vessel vasculitis affecting predominantly the respiratory tract and the kidneys Presented in the fifth decade , often with pulmonary symptoms Signs Respiratory tract Upper: perforation of the nasal septum Lower: nodular lesions , infiltrates and cavitaions Organs Necrotizing glomerulonephritis with renal failure Affects heart , spleen and adrenals Neurological: polyneuritis and meningoencephalitis Diagnosis: Anti-neutrophil cytoplasm antibodies Treated with systemic steriods and cyclophosphamide

Ophthalmic features Common : nasolacrimal obstruction and dacrycystitis Uncommon: scleritis and peripheral ulcerative keratitis Rare: orbital pseudo- tumour and occlusive retinal periarteritis Nasolacrimal duct involvement can result in epiphora, dacryocystitis and draining fistulas. sclerokeratitis  Dacrocystitis treated by surgey (Dacryocystorhinostomy ) . Good outcome

5.Hematologic disorders Hematological diseases encompass a wide spectrum of disorders ranging from benign to malignant conditions that can present with ocular involvement Ocular findings related to anemia, hematological malignancies and platelet disorders are to be disscussed

a. Anemia   Anemia is a common condition that occurs when the level of healthy RBCs or Hb is below normal Causes include: destruction, increased blood loss and inadequate production of RBCs by the bone marrow Additional causes related to poor nutrition or absorption defects in the GI tract include iron, vitamin B12or folic acid deficiencies general symptoms: pallor of the skin or nail beds, weakness, headaches, shortness of breath, GI disturbances, fever, and numbness or coldness of extremities Diagnosis: CBC is the most important, assess level of B12 and folic acid, bone marrow biopsy  

Ocular changes conjunctival pallor and hemorrhages  anemic retinopathy(intraretinal hemorrhages, Roth’s spot hemorrhages, cotton-wool spots, retinal exudates, venous dilation and optic nerve pallor) These changes generally occur in patients with severe anemia or when thrombocytopenia is present

Sickle cell anemia may also cause  sickled conjunctival vessels, central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), sickling maculopathy

b.

c. Platelets disorders Ocular changes can include : Conjunctival petechial hemorrhages Amaurosis fugax Vascular occlusions Retinal, vitreal and choroidal hemorrhages