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

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 mentioned in this presentation. CARISSA HINTZ, OD 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 Ocular Health Findings Pupils: PERRLA (-)APD OD/OS Anterior Segment:   EOMs: Full, no restrictions OU  OD: trace NS, 1+ cortical, 1+ PSC , deep & quiet anterior chamber (-)cells   OS: trace NS, 1+ cortical, trace PSC , deep & quiet anterior chamber (-)cells IOP by GAT: OD 66 OS 60  Posterior Segment: Gonioscopy: Open to CB 360, (-)PAS, flat iris approach    OD: glaucomatous cupping (0.85/0.85), otherwise unremarkable Pachymetry:   OS: glaucomatous cupping (0.75/0.75), otherwise unremarkable  OD: 495 microns  OS: 497 microns

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 Treatment and Follow-Up Angle Closure Initial treatment included Diamox, Simbrinza, timolol, Travatan Z and   Rhopressa. Glaucomatocyclitic Crisis  Lotemax and Nasacort were D/C.  Open-Angle Steroid Response Glaucoma  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. 

Long-term Treatment Mechanism In chronic steroid-induced glaucoma, normalization of IOP following D/C Steroid response glaucoma results in elevated IOP thought to be secondary to   of steroids usually takes 1-4 weeks. 7 increased outflow resistance. Thoughts on what causes this include:  2 weeks: IOP 18 OD and 16 OS  Upregulation of glucocorticoid receptors on TM cells. 1  Discussed treatment options: pt chose to pursue SLT  Glucocorticoids increase expression of fibronectin, glycosaminoglycans, and elastin. 9,10 1 day post-op SLT OD:   May suppress phagocytic activity leading to increased deposition in the  IOPs were 18 OU with Simbrinza TID OU and Travatan Z QHS OU. juxtacanalicular meshwork. 11 1 day post-op SLT OS: Glucocorticoid also decreases the synthesis of prostaglandin, which regulates   aqueous outflow. 2  IOPs 18 OD and 16 OS. 2 months post-op SLT:   IOPs 16 OU Epidemiology Response Categories Most studies have focused on adults, but children have been known to have  High steroid-responders: 4-6%  significant steroid responses to nasal sprays. 2  IOP >31mmHg  Steroid response glaucoma accounts for ¼ of acquired glaucoma in children! 2  Increase of >15mmHg from baseline Risk factors for being a steroid responder include: 2  Moderate steroid-responders: ~1/3   POAG patients (30% of glaucoma suspects and 90% of POAG might have an ocular  20-31mmHg hypertensive response to 4 week dose of dexamethasone.)  Increase of 6-15mmHg  First degree relatives of POAG patients Mild steroid-responders:   High myopia or history of refractive surgery or corneal transplant  <20mmHg  Very young and older patients (bimodal distribution)  Increase of <6mmHg  Diabetes Mellitus or connective tissue diseases like Rheumatoid Arthritis 8. Razeghinejad M, Katz L. Steroid-Induced Iatrogenic Glaucoma. Ophthalmic Res . 2012;47(2):66-80.  Eyes with pigment dispersion syndrome or traumatic angle recession Timeframe Steroid Response Steroid-response usually occurs 3-6 weeks following steroid use; however, it  can occur earlier. 13 by Risk It can take several months for corticosteroid injections to cause a steroid  response. 13 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.

Which Steroids are the Worst? Types of Intranasal Steroids  All forms of steroids can cause an IOP spike; however, the most at Generic Name Common Brands risk forms are topical (drops or ointment applied directly to the eyes Budesonide Entocort, Uceris, Pulmicort or eyelid skin), intravitreal, periocular, and inhaled corticosteroids st Generation like nasal sprays. 2 1 Beclomethasone Qvar  The pressure-inducing effect is directly proportional to the anti- dipropionate inflammatory potency and to the dosage used. 2 Triamcinolone acetonide Nasacort  Intra-nasal steroids come in 2 generations: 3 Mometasone furoate Nasonex  1 st generation: budesonide, beclomethasone dipropionate, and nd Generation triamcinolone acetonide. Higher systemic bioavailability compared to 2 Fluticasone proprionate Flonase 2 nd generation (up to 49%). High risk of steroid-response. Fluticasone furoate Veramyst  2 nd generation: mometasone furoate, fluticasone proprionate, and fluticasone furoate. Systemic bioavailability is <1%. Treatment Options Medical Therapy Class Mechanism Average IOP Reduction Discontinuation of steroids.   May need to substitute with non-steroidal option if anti-inflammatory is needed Prostaglandin Analogs Increase uveoscleral 20-35% Medical therapy should be initiated. outflow  Beta Blockers Decrease aqueous 20-25%  If medical therapy is insufficient, SLT should be considered followed by production glaucoma surgery if necessary. 2 Alpha-2 Agonists Reduce aqueous 20-25%  MIGS can also be considered if cataracts are visually significant to indicate cataract extraction. 3 production and increase uveoscleral outflow SLT appears to be effective for these patients according to multiple case  Carbonic Anhydrase Reduce aqueous 22% reports and studies. 4,12,14 Inhibitors production 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) 20. Schmidl D, Schmetterer L, Garhofer G, Popa-Cherecheanu A. Pharmacology of glaucoma. J Oculo Pharmacol Ther. 2015; 31(2): 63-77.

Latanoprostene bunod Netarsudil Rhopressa (netarsudil) 22   Vyzulta (latanoprostene bunod) 21  IOP reduction mechanisms:  Cleaves into latanoprost acid and a nitric oxide-donating  Increased outflow through the moity conventional pathway  decreased episcleral venous pressure  NO donors relax the TM and increase aqueous outflow  decreased aqueous production  Significantly greater IOP reduction compared to latanoprost  Latanoprost > Rhopressa ~ timolol  32% reduction in IOP  15-22% IOP reduction Netarsudil/latanoprost 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 of the TM. This increases TM outflow. 6  Rocklatan (netarsudil/latanoprost) 23  Can take up to 6 months for full IOP lowering effect to be reached. 5  Superior to netarsudil and latanoprost alone Trabectome: ablates the TM and decreases outflow resistance by opening a   Targets both the conventional and uveoscleral outflow direct pathway into Schlemm’s canal. 5  60% of patients achieve an IOP reduction of 30% or  Trabectome provides a safe and effective method to immediately lower IOP. 5 more Trabeculectomy or tube shunts may be considered if other methods do not  adequately lower IOP.  Nearly twice that of latanoprost alone 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  Laser targeting TM during Selective Laser Trabeculoplasty. 16