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A Unique Presentation of Steroid-Response The Presenter and - - PDF document

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A Unique Presentation of Steroid-Response The Presenter and Organizers for A Unique Presentation of Steroid-Response Glaucoma by Dr. Carissa Hintz has no Disclosures Glaucoma financial relationship with any company or products

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SLIDE 1

A Unique Presentation

  • f Steroid-Response

Glaucoma

CARISSA HINTZ, OD

Disclosures

 The Presenter and Organizers for “A

Unique Presentation of Steroid-Response Glaucoma” by Dr. Carissa Hintz has no financial relationship with any company

  • r products mentioned in this

presentation.

Case History

52 year old female referred for glaucoma evaluation

 Referring doctor noted IOPs of OD 56 and OS 53 by GAT 

Chief Complaint: referred for high IOP, blurred vision OD>OS, glare and difficulty with night driving that was progressing, no pain is noted

(+)FHx glaucoma: Father

Medications: Lipitor, Imitrex, Nexium, Singulair, natural progesterone/testosterone, lotemax 3x per week, Nasacort QD, steroidal rescue inhaler prn, lumify

Pt reports ocular health unremarkable besides myopia.

Pertinent Exam Findings

Pupils: PERRLA (-)APD OD/OS

EOMs: Full, no restrictions OU

IOP by GAT: OD 66 OS 60

Gonioscopy: Open to CB 360, (-)PAS, flat iris approach

Pachymetry:

 OD: 495 microns  OS: 497 microns

Ocular Health Findings

Anterior Segment:

 OD: trace NS, 1+ cortical, 1+ PSC, deep & quiet anterior chamber (-)cells  OS: trace NS, 1+ cortical, trace PSC, deep & quiet anterior chamber (-)cells 

Posterior Segment:

 OD: glaucomatous cupping (0.85/0.85), otherwise unremarkable  OS: glaucomatous cupping (0.75/0.75), otherwise unremarkable

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SLIDE 2
  • 18. Shihota R, Angmo D, Ramaswamy D, Dada T. Simplifying “target” intraocular pressure for

different stages of primary open-angle glaucoma and primary angle-closure glaucoma. Indian J Ophthmol. 2018; 66(4): 495-505.

Differential Diagnoses

Angle Closure

Glaucomatocyclitic Crisis

Open-Angle Steroid Response Glaucoma

Treatment and Follow-Up

Initial treatment included Diamox, Simbrinza, timolol, Travatan Z and Rhopressa.

Lotemax and Nasacort were D/C.

2 days later: IOP 10 OU

 Discontinue Rhopressa 

1 week: IOP 14 OD 13 OS

acetazolamide and timolol were D/C due to adverse effects.

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SLIDE 3

Long-term Treatment

In chronic steroid-induced glaucoma, normalization of IOP following D/C

  • f steroids usually takes 1-4 weeks.7

 2 weeks: IOP 18 OD and 16 OS  Discussed treatment options: pt chose to pursue SLT 

1 day post-op SLT OD:

 IOPs were 18 OU with Simbrinza TID OU and Travatan Z QHS OU. 

1 day post-op SLT OS:

 IOPs 18 OD and 16 OS. 

2 months post-op SLT:

 IOPs 16 OU

Mechanism

Steroid response glaucoma results in elevated IOP thought to be secondary to increased outflow resistance. Thoughts on what causes this include:

 Upregulation of glucocorticoid receptors on TM cells.1  Glucocorticoids increase expression of fibronectin, glycosaminoglycans, and elastin.9,10  May suppress phagocytic activity leading to increased deposition in the

juxtacanalicular meshwork.11  Glucocorticoid also decreases the synthesis of prostaglandin, which regulates aqueous outflow.2

Epidemiology

Most studies have focused on adults, but children have been known to have significant steroid responses to nasal sprays.2

 Steroid response glaucoma accounts for ¼ of acquired glaucoma in children!2 

Risk factors for being a steroid responder include:2

 POAG patients (30% of glaucoma suspects and 90% of POAG might have an ocular

hypertensive response to 4 week dose of dexamethasone.)

 First degree relatives of POAG patients  High myopia or history of refractive surgery or corneal transplant  Very young and older patients (bimodal distribution)  Diabetes Mellitus or connective tissue diseases like Rheumatoid Arthritis  Eyes with pigment dispersion syndrome or traumatic angle recession

Response Categories

High steroid-responders: 4-6%

 IOP >31mmHg  Increase of >15mmHg from baseline 

Moderate steroid-responders: ~1/3

 20-31mmHg  Increase of 6-15mmHg 

Mild steroid-responders:

 <20mmHg  Increase of <6mmHg

  • 8. Razeghinejad M, Katz L. Steroid-Induced Iatrogenic Glaucoma. Ophthalmic Res. 2012;47(2):66-80.

Steroid Response by Risk Factor

  • 2. Phulke S, Kaushik S, Kaur S, Pandav S. Steroid-induced Glaucoma: An Avoidable

Irreversible Blindness. Journal of Current Glaucoma Practice with DVD. 2017;11(2):67- 72.

Timeframe

Steroid-response usually occurs 3-6 weeks following steroid use; however, it can occur earlier.13

It can take several months for corticosteroid injections to cause a steroid response.13

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SLIDE 4

Which Steroids are the Worst?

 All forms of steroids can cause an IOP spike; however, the most at

risk forms are topical (drops or ointment applied directly to the eyes

  • r eyelid skin), intravitreal, periocular, and inhaled corticosteroids

like nasal sprays.2

 The pressure-inducing effect is directly proportional to the anti-

inflammatory potency and to the dosage used.2

 Intra-nasal steroids come in 2 generations:3  1st generation: budesonide, beclomethasone dipropionate, and triamcinolone acetonide. Higher systemic bioavailability compared to 2nd generation (up to 49%). High risk of steroid-response.  2nd generation: mometasone furoate, fluticasone proprionate, and fluticasone furoate. Systemic bioavailability is <1%.

Types of Intranasal Steroids

Generic Name Common Brands Budesonide Entocort, Uceris, Pulmicort 1

st Generation

Beclomethasone dipropionate Qvar Triamcinolone acetonide Nasacort Mometasone furoate Nasonex 2

nd Generation

Fluticasone proprionate Flonase Fluticasone furoate Veramyst

Treatment Options

Discontinuation of steroids.

 May need to substitute with non-steroidal option if anti-inflammatory is needed 

Medical therapy should be initiated.

 If medical therapy is insufficient, SLT should be considered followed by

glaucoma surgery if necessary.2

 MIGS can also be considered if cataracts are visually significant to indicate

cataract extraction.3  SLT appears to be effective for these patients according to multiple case reports and studies.4,12,14

Medical Therapy

Class Mechanism Average IOP Reduction Prostaglandin Analogs Increase uveoscleral

  • utflow

20-35% Beta Blockers Decrease aqueous production 20-25% Alpha-2 Agonists Reduce aqueous production and increase uveoscleral outflow 20-25% Carbonic Anhydrase Inhibitors Reduce aqueous production 22%

  • 20. Schmidl D, Schmetterer L, Garhofer G, Popa-Cherecheanu A. Pharmacology of
  • glaucoma. J Oculo Pharmacol Ther. 2015; 31(2): 63-77.
  • 20. Schmidl D, Schmetterer L, Garhofer G, Popa-Cherecheanu A. Pharmacology of
  • glaucoma. J Oculo Pharmacol Ther. 2015; 31(2): 63-77.

New Medications

 Latanoprostene bunod (Vyzulta)  Netarsudil (Rhopressa)  Netarsudil/latanoprost (Rocklatan)

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SLIDE 5

Latanoprostene bunod

 Vyzulta (latanoprostene bunod)21

 Cleaves into latanoprost acid and a nitric oxide-donating

moity

 NO donors relax the TM and increase aqueous outflow  Significantly greater IOP reduction compared to

latanoprost

 32% reduction in IOP

Netarsudil

Rhopressa (netarsudil)22

 IOP reduction mechanisms:  Increased outflow through the

conventional pathway

 decreased episcleral venous pressure  decreased aqueous production  Latanoprost > Rhopressa ~ timolol  15-22% IOP reduction

Netarsudil/latanoprost

 Rocklatan (netarsudil/latanoprost)23

 Superior to netarsudil and latanoprost alone  Targets both the conventional and uveoscleral outflow  60% of patients achieve an IOP reduction of 30% or

more

 Nearly twice that of latanoprost alone

Surgical Options

SLT: pigmented cells in the TM are targeted by a laser effectively destroying those cells and causing a signal for macrophages to increase activity at the site

  • f the TM. This increases TM outflow.6

 Can take up to 6 months for full IOP lowering effect to be reached.5 

Trabectome: ablates the TM and decreases outflow resistance by opening a direct pathway into Schlemm’s canal.5

 Trabectome provides a safe and effective method to immediately lower IOP.5 

Trabeculectomy or tube shunts may be considered if other methods do not adequately lower IOP. Laser targeting TM during Selective Laser Trabeculoplasty.16

SLT Efficacy

Maleki et al. reported 46.7% success rate in steroid-induced glaucoma (IOP <22 mmHg and/or >20% IOP reduction). At 12 months there was a 50.4% average IOP reduction.14

Xu et al. reported 61.7% success rate in POAG at 1 year (IOP <21mmHg with >20% IOP decrease or IOP <21mmHg with decrease in meds).17

Potential to reduce dependence on medications and to repeat treatment

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SLIDE 6

Follow-up Care of SLT

Complications:14,15

 Post-operative IOP spike  Usually within 4 hours of the procedure  Exfoliation glaucoma patients – higher risk of long-term IOP increase  Iritis  Rarely hyphema, macular edema, and corneal haze

SALT Trial

Studied impact of post-operative anti-inflammatories on efficacy of SLT

3 groups: NSAID, steroid, or placebo saline tears

NSAIDs and steroids following SLT resulted in significantly lower IOPs than placebo saline tears

 Baseline IOPs were not statistically different

  • 19. Growth SL, Albeiruti E, Nunez M, et al. SALT trial: steroids after laser trabeculoplasty. Ophthalmology. 126(11):

1511-1516.

  • 19. Growth SL, Albeiruti E, Nunez M, et al. SALT trial: steroids after laser trabeculoplasty. Ophthalmology.

126(11): 1511-1516.

Mechanism of SLT Theories

Mechanical theory:

 Thermal energy burns the tissues  Collagen shrinks and contracts  Uveoscleral meshwork and Schlemm’s canal are stretched open 

Cellular and molecular biologic theory:

 Laser energy stimulates cellular remodeling  Production of enzymatic metalloproteinases  Inflammation thought to play a role in TM remodeling  Inflammation can increase macrophage activity but may also elicit scarring/fibrosis

  • 19. Growth SL, Albeiruti E, Nunez M, et al. SALT trial: steroids after laser trabeculoplasty.
  • Ophthalmology. 126(11): 1511-1516.

SALT Conclusions

Medication in the first 5 days following SLT takes weeks to have an effect

  • n IOP

NSAIDS and steroids were thought to decrease scarring and fibrosis leading to greater IOP reduction

Surgeons were allowed to choose how many degrees to treat

Smaller studies have found no difference in efficacy between steroids and placebo

  • 19. Growth SL, Albeiruti E, Nunez M, et al. SALT trial: steroids after laser trabeculoplasty.
  • Ophthalmology. 126(11): 1511-1516.

Conclusion

Performing a thorough case history is vital especially since many patients forget to mention OTC nasal sprays when asked about medications.

Early detection is key as vision loss can occur rapidly if medical management is not initiated to reduce significantly elevated IOPs.

SLT is efficacious for steroid-response glaucoma

New studies are showing that NSAIDS following SLT may increase IOP- lowering efficacy.

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SLIDE 7

References

  • 1. Zhang X, Clark A, Yorio T. FK506-Binding Protein 51 Regulates Nuclear Transport of the Glucocorticoid

Receptor β and Glucocorticoid Responsiveness. Investigative Opthalmology & Visual Science. 2008;49(3):1037.

  • 2. Phulke S, Kaushik S, Kaur S, Pandav S. Steroid-induced Glaucoma: An Avoidable Irreversible
  • Blindness. Journal of Current Glaucoma Practice with DVD. 2017;11(2):67-72.

  • 3. Simsek A, Bayraktar C, Dogan S, Karatas M, Sarikaya Y. The effect of long-term use of intranasal

steroids on intraocular pressure. Clinical Ophthalmology. 2016:1079.

  • 4. SLT appears effective for steroid-induced glaucoma. Ophthalmology Times.

https://www.ophthalmologytimes.com/ophthalmology/slt-appears-effective-steroid-induced-

  • glaucoma. Published 2019. Accessed July 21, 2019.

  • 5. Ngai P, Kim G, Chak G, Lin K, Maeda M, Mosaed S. Outcome of primary trabeculotomy ab interno

(Trabectome) surgery in patients with steroid-induced glaucoma. Medicine (Baltimore). 2016;95(50).

  • 6. Noecker, MD, MBA R. How SLT Works. Glaucoma Today. 2019:30-31.

http://glaucomatoday.com/2005/04/0305_01.html/. Accessed July 21, 2019.

  • 7. Adam G, Michael R. The Will's Eye Manual: Office And Emergency Room Diagnosis And Treatment Of

Eye Disease. 6th ed. Wolters Kluwer; 2012:220-222.

  • 8. Razeghinejad M, Katz L. Steroid-Induced Iatrogenic Glaucoma. Ophthalmic Res. 2012;47(2):66-80.

References Continued

  • 9. Tschumper R, Johnson D, Bradley J, Acott T. Glycosaminoglycans of human trabecular meshwork in perfusion
  • rgan culture. Curr Eye Res. 1990;9(4):363-369.

  • 10. Steely T, Browdder S, Julian M, Miggans S, Wilson K, Clark A. The Effects of Dexamethasone on Fibronectin

Expression in Cultured Human Trabecular Meshwork Cells. Investigative Ophthalmology and Visual Science. 2019;33(7):2242-2250.

  • 11. Rohen J, Linnér E, Witmer R. Electron microscopic studies on the trabecular meshwork in two cases of

corticosteriod-glaucoma. Exp Eye Res. 1973;17(1):19-31.

  • 12. Rubin B, Taglienti A, Rothman R, Marcus C, Serle J. The Effect of Selective Laser Trabeculoplasty on

Intraocular Pressure in Patients With Intravitreal Steroid-induced Elevated Intraocular Pressure. J Glaucoma. 2008;17(4):287-292.

  • 13. Feroze KB, Khazaeni L. Steroid Induced Glaucoma. StatPearls Publishing. 2019.

  • 14. Zhou Y, Aref AA. A Review of Selective Laser Trabeculoplasty: Recent Findings and Current Perspectives.

Ophthalmol Ther. 2017; 6:19-32.

  • 15. Jha B, Bhartiya S, Sharma R, Arora T, Dada T. Selective Laser Trabeculoplasty: An Overview. Journal of

Current Glaucoma Practice. 2012; 6(2): 79-90.

  • 16. Mefford C. Selective Laser Trabeculoplasty: A Student Guide.

https://www.optometrystudents.com/pearl/selective-laser-trabeculoplasty-student-guide/. Accessed 2/16/20.

  • 17. Xu L et al. Efficacy of Low-Energy Selective Laser Trabeculoplasty on the Treatment of Primary Open Angle
  • Glaucoma. Int J Ophthalmol. 2019; 12(9): 1432-1437.

References Continued

  • 18. Shihota R, Angmo D, Ramaswamy D, Dada T. Simplifying “target” intraocular pressure for different

stages of primary open-angle glaucoma and primary angle-closure glaucoma. Indian J Ophthmol. 2018; 66(4): 495-505.

  • 19. Growth SL, Albeiruti E, Nunez M, et al. SALT trial: steroids after laser trabeculoplasty.
  • Ophthalmology. 126(11): 1511-1516.

  • 20. Schmidl D, Schmetterer L, Garhofer G, Popa-Cherecheanu A. Pharmacology of glaucoma. J

Oculo Pharmacol Ther. 2015; 31(2): 63-77.

  • 21. Weinreb RN, Ong T, Sforzolini BS, et al. A randomized, controlled comparison of latanoprostene

bunod and latoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015; 99(6): 738-745.

  • 22. Dasso L, Al-Khaled T, Sonty S, Aref AA. Profile of netarsudil ophthalmic solution and its potential in

the treatment of open-angle glaucoma: evidence to date. Clin Ophthalmol. 2018; 12: 1939-1944.

  • 23. Walters TR, Ahmed IK, Lewis RA, et al. Once-daily nedarsudil/latanoprost fixed-dose combination

for elevated intraocular pressure in the randomized phase 3 MERCURY-2 study. Opthalmology. 2019; 2(5): 280-289.