Some Basic Pearls. What Not to Refer. What would you do? Corneal Ulcer Example

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1 Some Basic Pearls Always treat within scope of practice as approved within your state (by legislature and/or State Board) SouthEast Eye Specialists Chattanooga Office What Not to Refer Zachary S. McCarty, OD Always treat within your comfort level Always treat with evidence-based medicine Corneal Ulcer Corneal Ulcer Example 25 YO WM Extended SCL wearer (silicone hydrogel) slept in lenses for 3 nights woke up with red, light-sensitive, painful OS 2 days ago Other ocular and systemic hx unremarkable No systemic or topical meds (other than red-eye drop) A. Refer to local ophthalmologist B. Diagnostic corneal scraping with pathology C. Initiate empirical treatment D. Refer to nearest corneal specialist BCVA: 20/20 OD 20/30 OS

2 Corneal Ulcers From one study: C. Initiate empirical treatment 69.1% culture-proven bacterial 22.2% no growth 4.9% fungal Further: 33 of 33 moderate infections improved without change in treatment 38 of 41 severe infections improved without change in treatment McLeod, SD, et al. The Roles of Smears, Cultures, and Antibiotic Sensitivity Testing in the Management of Suspected Infectious Keratitis. Ophthalmology 1996; 103:23-28 Why culture? Evidence-based treatment Identify infectious organism to modify treatment if NOT responding to empirical therapy Retrospective study showed only 20% of infectious keratitis cases properly cultured by community ophthalmologists (California) If ulcer has/is: Case history NOT suggestive of microbial cause other than bacteria (wearing contact lenses recently in lake or hot tub, contact with vegetative matter) peripheral less than 2 mm in size McDonnell, et al. Community Care of Corneal Ulcers. Am J Ophthalmol 1992; 114(5):531-8 McLeod, SD, et al. The Roles of Smears, Cultures, and Antibiotic Sensitivity Testing in the Management of Suspected Infectious Keratitis. Ophthalmology 1996; 103:23-28 Evidence-based treatment Example of corneal ulcer documentation Documentation of size and location of both INFILTRATE & EPITHELIAL STAIN 4th generation fluoroquinolone every 15 min for first hour Continue antibiotic hourly for first day Daily follow-up Can decrease frequency of antibiotic as ulcer heals Corneal Ulcer OS: 10:30 mid-periphery 1.5 mm H x 1.5 mm V infiltrate 1 mm H x 1 mm V epithelial stain 5% thinning centrally in ulcer 5-10 cell HPF (no hypopyon)

3 Evidence-based treatment What about culture after starting antibiotics? expect improvement of pain within 1-2 days slow resolution of epithelial defect resolution of any anterior chamber reaction (no change or development of new hypopyon) have protocol in place for referral to a specialist for culture if conditions worsen However, if the antibiotic is effective against the organism, then treatment modification and, therefore, subsequent cultures ought not be necessary. If antibiotic non-effective, shouldn t interfere with later culture McLeod, SD, et al. The Roles of Smears, Cultures, and Antibiotic Sensitivity Testing in the Management of Suspected Infectious Keratitis. Ophthalmology 1996; 103:23-28 Corneal Ulcer Summary Mild Ulcer no culture 4th Generation fluoroquinolone Moderate Ulcer culture Fortified Tobramycin (14 mg/ml), Fortified Vancomycin (25-50 mg/ml), 4th Generation fluoroquinolone (every hour rotating) Severe Ulcer Herpes Simplex Keratitis (HSK) Consider referral Herpes Simplex Epithelial Keratitis 36 year old white male blurry vision and redness OD cornea OD: central dendritic ulcer No history of previous red eye A. Refer to a local corneal specialist B. Perform corneal debridement C. Begin topical anti-viral therapy D. Begin oral anti-viral therapy

4 Evidence based treatment for Herpes Simplex Epithelial Keratitis Viroptic (1% Trifluridine ophthalmic solution) One drop q2h up to nine times per day until corneal ulcer heals then five times daily for 7 days C. Begin topical anti-viral therapy Zirgan (0.15% Ganciclovir ophthalmic gel) Instill five times daily until corneal ulcer heals then three times daily for 7 days Zovirax (3% Acyclovir ophthalmic ointment) Available outside the U.S. Instill five times daily until corneal ulcer heals then continue five times daily for 3 additional days 1.WilhelmusKR.Antiviraltreatmentandothertherapeuticinterventionsforherpessimplexvirusepithelialkeratitis.Cochrane Database of Systematic Reviews 2010, Issue Croxtall JD. Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers). Drugs Mar 26;71(5): Ganciclovir ophthalmic gel, 0.15%: A Valuable Tool for Treating Ocular Herpes. Clinical Ophthalmology Dec; 1(4): Corneal Toxicity with Topical Anti-viral Agents Zirgan is selective against viral and INFECTED host cell DNA while Viroptic inhibits viral and HEALTHY host cell DNA synthesis As a result, Viroptic has a significant potential for toxicity to the cornea and other ocular tissues Zirgan is less likely to cause corneal toxicity and has been shown to be well-tolerated 1. La Lau C, Oosterhuis JA, Versteeg J, et al. Aciclovir and trifluorothymidine in herpetic keratitis. Preliminary report of a multicentered trial. Doc Ophthalmol Mar 20;50(2): Naito T, Shiota H, Mimura Y. Side effects in the treatment of herpetic keratitis. Curr Eye Res Jan;6(1): Maudgal PC, Van Damme B, Missotten L. Corneal epithelial dysplasia after trifluridine use. Graefes Arch Clin Exp Ophthalmol. 1983;220(1): Croxtall JD. Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers). Drugs Mar 26;71(5): Oral Anti-virals in Herpes Simplex Epithelial Keratitis Treatment Oral Acyclovir has shown a similar efficacy as topical Acyclovir in the treatment of Herpes Simplex Epithelial Keratitis Zovirax (acyclovir) 400mg five times daily for seven to ten days Valtrex (valacylovir) 500mg three times daily for seven to ten day Famvir (famciclovir) 250mg three times daily for seven to ten days Oral Acyclovir has been shown to lower the recurrence rate of Herpes Simplex Epithelial Keratitis dosage of acyclovir is 400mg PO 2 times a day for prophylaxis 1.Collum LM, McGettrick P, Akhtar J, et al. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration. Br J Ophthalmol Jun; 70(6): The Herpetic Eye Disease Study Group: Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med 339: , Posterior Vitreous Detachment (PVD)

5 PVD example 53 YO female Flashes of light in a semi-circular, crescent pattern more noticeable in the dark - OD No pain or decreased vision BCVA: 20/20 OD 20/20 OS IOP: 15 mmhg 16 SLEx: unremarkable OU A. Refer to local ophthalmologist B. Monitor and follow-up per literature guidelines C. Refer to a retinal specialist for full retinal eval D. Reassure patient and re-appoint in 1 year DFEx: PVD literature guidelines B. Monitor and follow-up per literature guidelines Patients with acute PVD, WITHOUT retinal breaks 2-5% chance of developing (RD) in following weeks If present with vitreous hemorrhage 67-71% found to have at least one break 31% found to have more than one break 88% of breaks occur in superior quadrant - Dayan, MR, Jayamanne DG, Andrews RM, Griffiths PG. Flashes and floaters as predictors of vitreoretinal pathology: is follow-up necessary for posterior vitreous detachment? Eye 1996; 10: van Overdam KA, Bettink-Remeijer MW, Mulder PG, van Meurs JC. Symptoms predictive for the later development of retinal breaks. Arch Ophthalmol 2001; 119: Richardson PSR, Benson MT, Kirby GR. The posterior vitreous detachment clinic: do new retinal breaks develop in the six weeks following an isolated symptomatic posterior vitreous detachment? Eye 1999; 13: Sarrafizadeh R, Hassan, TS, Ruby AJ, et al. Incidence of retinal detachment and visual outcome in eyes presenting with posterior vitreous separation and dense fundus-obsuring vitreous hemorrhage. Ophthalmology 2001; 108: PVD literature guidelines PVD literature guidelines Patients with acute PVD without retinal break Protocol for patient with suspected PVD without vitreous hemorrhage peripheral retinal examination is REQUIRED preferably with BIO. without Shafer s sign Scleral depression is highly recommended Anterior vitreous examination at slit lamp for Shafer s sign (aka tobacco dust ) without visible vitreoretinal traction Can be evaluated again within 6 weeks Always counsel on further risk factors and RTC sooner if experience any - Brockhurst RJ. Modern Indirect ophthalmoscopy. Am J Ophthalmol 1956; 41: Dayan, MR, Jayamanne DG, Andrews RM, Griffiths PG. Flashes and floaters as predictors of vitreoretinal pathology: is follow-up necessary for posterior vitreous detachment? Eye 1996; 10:456-8.

6 Symptomatic Vitreomacular Traction What about ocriplasmin intravitreal injection (Jetrea, ThromboGenics NV)? Can be treated with ocriplasmin intravitreal injection Indications: patient is symptomatic area of vitreomacular traction with foveal elevation or small macular hole (less than 250 µm) Exclusions, patient with: epiretinal membrane (ERM) - most common cause for failure wet AMD diabetic macular edema Jetrea Outcomes 26.5% had resolved VMA at 28 days (10.1% for placebo) 40.6% had nonsurgical closure of macular hole (10.6% for placebo) Stalmans P et al. N Engl J Med 2012;367: Stalmans P et al. N Engl J Med 2012;367: Stalmans P et al. N Engl J Med 2012;367: Stalmans P et al. N Engl J Med 2012;367:

7 Jetrea side effects For up to 24 hours after injection patient may experience flashing lights (photopsia) Additional floaters Uveitis Little to no injection-related pain Conjunctival hemorrhage Stalmans P et al. N Engl J Med 2012;367: Anterior Uveitis 23 year-old white female redness and light sensitivity OS cornea: see photo anterior chamber cells/hpf no previous occurrence, no contact lens wear A. Write an order for laboratory testing B. Begin topical anti-inflammatory treatment C. Schedule consult with a local rheumatologist D. Refer the patient to a local ophthalmologist Evidence Based Treatment of Anterior Uveitis B. Begin topical anti-inflammatory treatment The general goals for therapy in anterior uveitis are: To preserve visual acuity To relieve ocular pain To eliminate the ocular inflammation To prevent formation of synechiae To manage intraocular pressure

8 Evidence Based Treatment of Acute Anterior Uveitis The mainstay of acute anterior uveitis treatment involves topical corticosteroids The dosing of topical corticosteroids should be tailored to the severity of the AC inflammation --->hit the anterior chamber inflammation hard early on in its course with intensive topical steroids Ester-based topical corticosteroids (i.e. Lotemax) are metabolized more readily and have been shown to exhibit lower concentrations in the anterior chamber than ketonebased steroids (i.e. prednisolone) 1.Wakefield D, Chang JH, Amjadi S, Maconochie Z, Abu El-Asrar A, McCluskey P. What is new HLA-B27 acute anterior uveitis. Ocul Immunol Inflamm Apr;19(2): Comstock, Timothy L, DeCory, Heleen H. Advances in Corticosteroid Therapy for Ocular Inflammation: Loteprednol Etabonate. International Journal of Inflammation Evidence Based Treatment of Acute Anterior Uveitis The topical steroid should be dosed frequently to assure high concentrations are achieved in the anterior chamber Durezol (difluprednate ophthalmic emulsion 0.05%) is also an effective steroid option for inflammation control Durezol administered qid is at least as effective as pred forte 1% administered 8x/day in resolving the inflammation and pain associated with endogenous anterior uveitis 1.Foster CS, Davanzo R, Flynn TE, McLeod K, Vogel R, Crockett RS. Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther Oct;26(5): Pearls in Anterior Uveitis Treatment Formulation and dosing of steroids are critical to uveitis treatment Specify Brand Frequent dosing initially, slow taper over time Glaucoma (Follow-up) Utilize cycloplegic agents to aid in inflammation control Beware of posterior synechiae in the dilated position Monitor intraocular pressure for steroid response Glaucoma example 70 YO WF Referred as a glaucoma suspect BCVA: 20/20 OD 20/20 OS IOP: 14 mmhg OD 19 mmhg Pachs: 520 µm OD 525 µm OS VF:

9 Visual Field OS OD A. Refer to regional glaucoma specialist for monitoring B. See patient yearly for vision exam and spectacle update C. Refer to local ophthalmologist for medical care D. Continue standard of care follow-up in-office Plan D. Continue standard of care follow-up in-office Initiate topical prostaglandin QHS OU Target IOP: 11 mmhg OD 14 mmhg OS Continue VF testing every 4 mo (initially) IOP over 5 years OS Visual Fields OD IOP OD IOP OS Target OD Target OS 0 4/28/09 5/26/09 8/31/09 11/30/09 4/27/10 8/24/10 12/14/10 4/12/11 11/22/11 5/2/12 10/29/12 3/4/13 9/30/13 1/28/14

10 Next Plan Evidence-based Glaucoma 6 major studies: Ocular Hypertension Treatment Study (OHTS) Continue prostaglandin QHS OU Schedule cataract extraction OU Collaborative Initial Glaucoma Treatment Study (CIGTS) Early Manifest Glaucoma Trial (EMGT) Collaborative Normal-Tension Glaucoma Study (CNTG) Advanced Glaucoma Intervention Study (AGIS) Tube vs Trabeculectomy Study (TVT) Shrivastava A, Singh K. The impact of cataract surgery on glaucoma care. Curr Opin Ophthalmol Jan;25(1): OHTS - Key Findings OHTS - Take Home Message When indicated, treating IOP with topical medications delays or prevents glaucomatous damage (first study) At five years, decreasing IOP by 20% reduced incidence of glaucoma by 60% vs observation At 10 years, incidence of glaucoma was reduced greatest in the high risk group from 42% to 19% (low risk group was only 7% to 4%) Consider risk categories (low, medium, and high - based on IOP, age, CCT, vertical C/D ratio, & PSD) Consider observation before treatment in some patients (low risk?) Only 10-20% of ocular hypertensives develop glaucoma Kass MA et al. Arch Ophthalmol. 2002;120(6) Kass MA et al. Arch Ophthalmol. 2002;120(6) OHTS - Risk Categories CIGTS - Key Findings Aggressive IOP targets yield results (achieved 35% in medical treatment arm and 48% with surgery) Looked at quality of life as an outcome IOP vs CCT CD ratio (vertical) vs CCT Musch DC et al. Ophthalmology. 1999;106(4):

11 CIGTS - Take Home Message EMGT - Key Findings Discuss fear of blindness Surgery may need to be considered first in moderate or advanced glaucoma (MD -10 db HVF were more likely to show progression on medicine) African-American patients did not fare as well with surgery-first approach Keep IOP steady - Variability in IOP is highly unfavorable Further confirmed that pressure lowering is beneficial in glaucoma treatment Depending on analysis, every 1 mmhg of lowering could be 10-13% risk reduction Rate of glaucoma progression is variable and still difficult to predict Mean IOP vs fluctuation is what matters Musch DC et al. Ophthalmology. 1999;106(4): Lichter PR et al. Ophthalmology. 2001;108(11): Heijl A et al. Arch Ophthalmol. 2002;120(10): EMGT - Take Home Message CNTG - Key Findings Follow for progression closely and reset target as needed (suggested VF and IOP every 4 months for first 2 years) Persist in lowering by that extra 1 mmhg Exfoliation is a high risk factor - doubled risk of developing field loss in nine years NTG progression was slower in the treated group vs untreated group (big shock as pathogenesis of NTG was hotly debated) Heijl A et al. Arch Ophthalmol. 2002;120(10): Grodum K et al. Ophthalmology. 2005;112(3): Anderson DR. Curr Opin Ophthalmol. 2003;14(2):86-90 CNTG - Take Home Message AGIS - Key Findings Distinguish between progressive and nonprogressive disease 50% did not progress in 5-7 years without treatment Reducing IOP slows visual field loss (ATT vs TAT) Goal to lower IOP by 30% (achieved with SLT and meds in 75-80% of patients) Double-check progression with frequent VF testing - sometimes 5-6 VF confirmations were needed to avoid overdiagnosis of decline 2/3 remained stable Race affected outcomes - African Americans overall consistently fared worse Anderson DR. Curr Opin Ophthalmol. 2003;14(2):86-90 The Advanced Glaucoma Intervention Study (AGIS). Control Clin Trials. 1994;15(4):

12 AGIS - Take Home Message TVT - Key Findings Trab vs shunt = no clear winner Tailor treatment based on ethnicity - consider ALT (now SLT) first line for African-Americans Very small differences - tube shunt had a slightly higher long term success rate Trabeculectomy with MMC had better pressure control in first three months Only enrolled patients at low risk of surgical failure The Advanced Glaucoma Intervention Study (AGIS). Control Clin Trials. 1994;15(4): Gedde SJ et al. Am J Ophthalmol. 2009;148(5): Minkler DS et al. Ophthalmology. 2008;115(6): Glaucoma Summary Frequent VF testing to establish progression Consider risk factors when opting to observe vs treat What about this one? Lower IOP from baseline by 20-30% (every mmhg can count) IOP OS Visual Fields OD IOP OD IOP OS Target 0 6/29/12 8/29/12 3/4/13 8/7/13 2/11/14

13 What about this one? 0 IOP Added timolol to prostaglandin 4 IOP OD IOP OS 2 8/21/08 12/5/08 2/23/09 9/3/09 2/4/10 7/15/10 12/16/10 1/12/11 3/3/11 4/29/11 5/11/11 9/1/11 4/19/12 5/31/12 8/27/12 1/28/13 4/22/13 9/9/13 11/12/13 1/13/14 OS Visual Fields OD