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Ocular complications of corticosteroids

Ocular complications of corticosteroids. Hani Levkovitch-Verbin. Ocular complications of steroids. Secondary to Ocular: Drops Injections Sub-conjunctival Sub-tenon Periocular Intravitreal. Steroids complications. Systemic: Oral Intravenous Intranasal Inhalation

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Ocular complications of corticosteroids

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  1. Ocular complications of corticosteroids Hani Levkovitch-Verbin

  2. Ocular complications of steroids Secondary to • Ocular: • Drops • Injections • Sub-conjunctival • Sub-tenon • Periocular • Intravitreal

  3. Steroids complications • Systemic: • Oral • Intravenous • Intranasal • Inhalation • Cutaneous - topical • Epidural injections

  4. Steroids complications • Conjunctival necrosis • Corneal stromal calcification • Delayed corneal wound healing • Glaucoma and ocular hypertension • Cataract • Retinal/choroidal emboli • Central serous chorioretinopathy • Decreased resistance to infection

  5. Conjunctival necrosis • Following subconjunctival injections of methyprednisolone or triamcinolone. • Few articles with case reports. • Negative cultures • The lesions healed in 2-4 weeks after excision of the injected material

  6. Corneal stromal calcification • Only secondary to topical steroids with phosphate preparation. • M/P due to precipitation of calcium phosphate.

  7. Cataract • Posterior subcapsular cataract • Following administration by: • Topical • Subconjunctival • Systemic • Inhalation • Nasal sprays

  8. Incidence of steroids induced cataract • Depends on dose, duration and individual sensitivity. • Minimal time reported was 2 months of 5 mg/day. Usual time required is 1 year of 10mg/day prednisone. • 10%-40% of patients treated by oral steroids will develop cataract. • Inhalation cause more cataract than nasal spray m/p due to systemic and topical effect.

  9. Retinal/choroidal emboli • Following injections: • Periocular • Retrobulbar • Intralesional injections to chalazion • Tonsillar • Nasal • Scalp • Aggregates of microcrystals gained access to the ophthalmic arterial system via retrograde flow

  10. CSR • Oral • Injections • Inhalations • Endogenous hypercortisolism Mechanism - inborn or acquired susceptibility of the posterior BRB??.

  11. Steroids, ocular hypertension and glaucoma • First described in 1950. • Well documented after 3-6 weeks of treatment topically or systemic. • Patients may develop marked elevation of IOP after months of therapy. • Acute IOP elevation - rare

  12. Secondary to: Systemic : • Oral • IV • Topical cutaneous • Inhalations • Nasal Ocular: • Topical • Intravitreal • Periocular

  13. Steroid induced glaucoma • Similar to POAG • Ocular hypertension • Open angle • Optic nerve cupping • VF loss • IOP usually returns to normal within 2-4 weeks after stopping topical treatment. In some cases it may remain elevated.

  14. Steroid induced glaucoma • Armaly (IOVS 1964) • Healthy individuals with normal eyes • Topical treatment for 4-6 weeks • 4-6% were high responders with IOP elevation >15mmHg and IOP >31 mmHg

  15. Steroid induced glaucoma • 30% developed moderated response with IOP elevation of 6-15 mmHg and IOP between 20-31 mmHg • 65% were non-responders with less than 6 mmHg elevation and IOP less than 20 mmHg.

  16. Risk factors • Patients with POAG - more than 50% may develop significant IOP rise • Relatives of patients with POAG • Myopia?? • Diabetes mellitus?? • Connective tissue diseases??

  17. Acute IOP elevation • Systemic steroids may increase rapidly the IOP in POAG patients . • The IOP increased following the rise in plasma cortisol. • IOP was elevated in 3-9 mmHg within 4-8 hours following dexamethasone dose. RN Weinreb et al, IOVS, 1985

  18. Mechanism • Recently (Lo et al, Tissue differential microarray analysis of dexamethasone induction reveals potential mechanisms of steroid glaucoma IOVS feb 2003), it was found that dexamethasone treatment causes specific upregulation of the TIGR/MYOC gene in the human TM cells but not in other cells. • TIGR/MYOC is a 504-amino-acid secretory protein found normally in the cilliary body, human retina, ONH astrocytes and skeletal muscle.

  19. TIGR/MYOC protein • Mutations in TIGR/MYOC gene have been linked to glaucoma. • More then 25 mutations in TIGR/MYOC gene were discovered in families with POAG and JOAG. • The function of this gene is currently unknown

  20. TIGR/MYOC gene • Mutations in this gene lead to impaired secretion of the protein resulting in misfolding and accumulation of aggregates inside the cells.

  21. Genetics of glaucoma • Mutation in TIGR/MYOC are only linked to glaucoma and do not affect the function of any other organ. • It is postulated that TIGR/MYOC protein serves TM specific function that could be integral to glaucoma pathophysiology. • Myoc-knockout mice are viable, have normal IOP and normal ocular morphology.

  22. Mutations in TIGR/MYOC – may lead to glaucoma • Upregulation of the TIGR/MYOC gene and overproduction of myocilin protein due to steroid treatment leads to ocular hypertension.

  23. Gene expression changes induced by Dexamethasone in human TM cells • Using a cDNA microarray it was found that Dexamethasone treatment cause upregulation and downregulation of several genes. • Some of them represent components of the extracellular matrix and thus may be responsible for the reduction in outflow facility. Ishibashi et al. IOVS 2002

  24. Treatment Systemic steroids induced glaucoma • If possible fast tapering or change drug • Anti-glaucoma eye drops (Tiloptic, Trusopt, Xalatan, Alphagan, Iopidine). • Systemic Diamox or Neptazan- for short term treatment • Uncontrolled under MTMT- consider ALT or surgery

  25. Treatment Topical steroids induced glaucoma: • Stop or tapered quickly. • Change to less effective steroid • Change to NSAID (Voltaren Ophtha). • Anti-glaucoma eye drops • Don’t be aggressive if optic nerve and VF are normal • Close follow-up

  26. Steroids Vs. NSAID’s • Diclofenac and dexamethasone were equally effective in reducing postoperative inflammation after: • Cataract surgery • Strabismus surgery • LASIK • Trabeculectomy with MMC

  27. Be aware !!! • Retinal specialists: • Postop dexamycin after RD op and vitrectomies • Intravitreal Kenalog • Corneal specialists • Topical steroids following PKP • Topical steroids following LASIK • Long term use of steroidal drops for keratoconjunctivitis and other ocular surface diseases

  28. Don’t forget to measure IOP: • Pediatric ophthalmologists: • Strabismus surgeries • Cataract surgeries • Oculoplastic specialists • Grave’s disease

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