MEDICAL THERAPY OF GLAUCOMA

Transcription

1 MANAGING GLAUCOMA MEDICAL THERAPY OF GLAUCOMA The goal of treatment in glaucoma is to reduce IOP to a level below which optic nerve and visual field damage will not occur or progression of existing damage is prevented. MEDICAL THERAPY OF GLAUCOMA Decision to treat Target pressures Low risk- monitor Progression- amplify therapy Periodic observation Never change therapy based upon one bad IOP or field Climbing the therapeutic ladder MANAGING GLAUCOMA Based upon diagnostic evaluation, weighing risk factors, and considering risk-to-benefit ratio of treatment, the decision to initiate medical therapy is made. Once the decision to treat is made, a goal of therapy is set. In some cases, a target pressure is chosen. This pressure (or range) is the one that is felt to be a safe level for a given patient. THE MYTH OF 21 There is no guarantee that IOP less than 21 will preserve a patient s vision or greater will result in blindness. The greater the degree of damage, the lower the IOP needs to be due to fragility of the already damaged nerve. Past progression predicts future progression unless IOP is lowered CHANDLER AND GRANT- 1960S Eyes with advanced cupping require pressures below the average of the population. Eyes with limited cupping, confined to one pole of the disc, appear to withstand tension better. Eyes with a normal disc appear to withstand pressure well over many years. The appearance of the disc may serve as an important guide to the management of glaucoma. 1

2 Mean change in visual defect score 6/21/2018 TARGET IOP A clinical GPS How do you get there if you don t know where you are going? Is it important? Yes How do I figure it out? That s not so easy To get where you re going, don t forget where you have been. - Peak IOP Should we do it? Do we do it? Set an initial target pressure of at least 25% lower than pretreatment IOP. Choosing a lower target IOP can be justified if there is more severe optic nerve damage. Target pressure is an estimate and must be individualized and/or adjusted during the course of the disease The goal of treatment is to maintain the IOP in a range at which visual field loss is unlikely to significantly reduce a patient s health-related quality of life over his/her lifetime If progression occurs at the target pressure, undetected IOP fluctuations and adherence to therapy should be re-evaluated before adjusting target IOP downward Assess the patient who is being treated with glaucoma medication for local ocular and systemic side effects TARGET IOP Practice guidelines recommend target IOP - Should be written in chart - Rarely done so Determining initial target pressure - Existing disc damage - Extent of field damage - Risk of imminent/ future functional disability Rate of change impacts target IOP - Patient age and life expectancy - Peak IOP B should have lower target IOP than A A B AGIS 7: SUSTAINED IOP BELOW 18 MM HG: POSITIVE CORRELATION WITH STABILITY OF VISUAL FIELD Percent of Visits with IOP Less Than 18 mm Hg 100% of visits 75-99% of visits 50-74% of visits 0-49% of visits Follow-up (years) AGIS Investigators, 2000, Am. J. Ophthalmol., 130,

3 PERCENTAGE DECREASE FROM BASELINE Can the studies guide us? Clinical trials provide Evidence and Guidelines - Take care to apply the correct study to the correct population Understand how and why target pressures are chosen for clinical studies INFORMATION FROM MAJOR STUDIES Study IOP reduction Progression OHTS 20% Yes EMGT 25% Yes CNTGS 30% Yes CIGTS (med) 35% No CIGTS (Surg) 48% No AGIS < 18 all visits No CIGTS overall had no field change At 1, 3, and 5 years after treatment initiation, the percentage showing progression (6.6%, 10.9%, and 14.5%, respectively) and improvement (7.5%, 12.7%, and 13.9%, respectively) differed minimally and the increasing trends in both loss and improvement were similar. Roughly the same number of patients improved as progressed. Predictive factors for VF improvement included several indicators of better IOP control, which supports the postulate that VF improvement was real. When low IOP can be safely achieved- do it. A target pressure is that pressure at which the sum of the impact of the glaucomatous vision loss upon the patient and the impact of treatment upon the patient is minimized. Once treatment is started, the goal is not to make the IOP normal, but safe for the patient. Demand greater reductions than before % vs 20-30%, especially for advanced disease/ risk of visual disability. Am I at medicolegal risk if I don t have target in chart? No Am I at medicolegal risk if I have target in chart and I don t reach it? No WHICH IS BETTER? ONE OR TWO? Pt 1: treated 20 mm Pt 2: treated 15 mm WHICH IS BETTER? ONE OR TWO? Pt 1: Ta max 42 mm- treated 20 mm Pt 2: Ta max 20 mm- treated 15 mm 3

4 TARGET IOP: A BEST GUESS BASED UPON: Age and longevity - Don t be age-prejudiced Degree of optic nerve damage Degree of visual field loss Threat to fixation and risk of disability IOP at which damage occurred Corneal thickness Family history of glaucoma blindness TARGET IOP It doesn t have to be symmetrical It doesn t have to be exact It must remain fluid Be aware of peak IOP 61 YOM; recently dx ed with POAG OD; OHTN OS; started on latanoprost OU CCT: 556 OD, 543 OS REASSESSING TARGET IOP 72 YOBF: POAG OU x 6 years Initial IOP 28 mm Treated IOP: 15 mm - Can tolerate only 1 PGA as MMT - Adverse reactions with all other meds - Still an acceptable response, right? REASSESSING TARGET IOP 68 YOF- OHTN 4

5 REASSESSING TARGET IOP Treatment advocated- pt declines; agrees to close observation 3 mos f/u scheduled- returns 3 years later Best management now? THE GOOD OLD DAYS! Climbing the Therapeutic Ladder Surgery Diamox Pilocarpine Propine Timoptic 5

6 % Reduction in IOP 6/21/2018 Medical Therapy Today FIRST CHOICE MONOTHERAPY MEDICAL THERAPY OF GLAUCOMA EFFECTIVE ON IOP VERIFY TOLERABILITY Target IOP reached Continue Target IOP maintained PERIODICALLY VERIFY END POINTS n Quality of life n Visual field n Optic disc n IOP Target IOP reached Target IOP not reached Add 2 nd drug Target IOP not reached Substitute the 2 nd drug Effective on IOP NON-EFFECTIVE ON IOP CHANGE MONOTHERAPY Other therapeutic options eg, surgery, laser, etc Non-effective on IOP If poor response to several different medications, consider non-compliance Flowchart VIII. European Glaucoma Society. Terminology and Guidelines for Glaucoma. Savona, Italy: DOGMA Srl; When to initiate and amplify therapy Medical contraindications Monotherapy, polytherapy, adjunctive therapy Target pressures - Major glaucoma study guidelines When to judge efficacy Myth of monocular trials Climbing the therapeutic tree Synergy/ non-synergy AGENTS USED IN COMBINATION WITH PROSTAGLANDINS: EFFECT ON IOP 0-1 Change in IOP P = Brimonidine Beta-blocker CAI (BID or TID) O Connor DJ, et al. Am J Ophthalmol. 2002;133: PERCENT OF PATIENTS ACHIEVING 10% OR GREATER REDUCTION IN IOP FROM LATANOPROST BASELINE PERCENT REDUCTION IN IOP FOR TIMOLOL, BRINZOLAMIDE, AND BRIMONIDINE ADDED TO TRAVOPROST 90 84% 0 % % % Alpha Agonists Beta-Blockers TCAIs Alpha Agonists Beta-Blockers TCAIs O Connor DJ, et al. Am J Ophthalmol. 2002;133: /- 7.5% Adjunctive Agent /- 9.1% /- 8.6% Reis R, et al. Clin Ther 2006;28: timolol brinzolamide brimonidine 6

7 WHAT IS MAXIMAL MEDICAL THERAPY? A mutually agreed upon regimen between doctor and patient - Some practitioners will not put patients on any more than two medications and others will use three or four - Patients may be accepting of multiple meds if surgery the next option Laser trabeculoplasty is an option if medications are insufficient Surgery is an option if medications and/or laser fail BIASES IN GLAUCOMA MANAGEMENT Medications don t work as well as we think - Average IOP reductions in clinical trials Some respond much better and some don t respond at all - Tachyphylaxis - Adherence Surgery is not as risky as we think - CIGTS; TVT Definite complications, but most self limited or easily managed MEDICAL THERAPY OF GLAUCOMA Unless the patient is at risk of imminent vision loss from an undiagnosed case of advanced glaucoma, get several untreated IOP readings over time before beginning therapy. There is absolutely no reason to heroically lower IOP in office in patients with chronic glaucoma. Treating a blind eye is recommended to avoid pain and maintain cosmesis TERMINOLOGY Compliance: The act of conforming, acquiescing, or yielding; cooperation or obedience - Pejorative term TERMINOLOGY TERMINOLOGY Adherence: A measure of the degree to which a patient follows prescribed instructions during a defined time period. - E.g. Timolol BID over 30 days; patient uses 20 drops; adherence is 33% - Allows the patient to have lapses in drug use and summarizes the percent of days that the patient uses the drug 41%- 76% adherence in glaucoma Persistence: A metric that evaluates the time until a patient first discontinues the use of a medication. - BID drug used QD and patient refills each month and stockpiles medication has excellent persistence (100%) and poor adherence (50%) White Coat Adherence: Patient adherence rises sharply 1 week before examination and then declines 30 days following 7

8 ADHERENCE BY DRUG CLASS AND THERAPY MEASURING ADHERENCE PGAs have higher degree of persistence and adherence Nearly half of monotherapy patients had stopped using medications at 6 months Less adherence and persistence with polytherapy A second drug leads to reduced filling of first-prescribed medication Self-reporting - Universally greatly overestimated 97% self-reporting and 99% medication logs vs 76% on electronic monitoring Electronic monitoring - Theoretically most accurate - Not practical in most situations - Reports that patient used medication, not that it went into the eye Does not confirm placement in the eye. Patients have been known to dump medication when they know they are being electronically monitored. Pharmacy records - Little information on timeliness or consistency - No record on free samples BARRIERS TO ADHERENCE AND PERSISTENCE Cost Tolerability Dosing schedule Denial Lack of education about disease Forgetfulness Travel Schedule 8

9 1 MONTH MAX THERAPY Branded: approximately $400/month Generic: approximately $60/month INDICATIONS FOR NON-ADHERENCE DETECTING NON-ADHERENCE High IOP at follow up - Meds don t fail overnight Lack of complaints about adverse effects Visit default - Rates of admitted non-adherence higher among visit defaulters - Worse adherence correlates with worse follow up Progression despite seemingly good IOP Patient resists further treatment No-shows Caregiver report Lack of refills - Rx lasts abnormally long Ask about last dose - Open ended questions, not yes/no Poor understanding Patient confesses Vague or no reports about adverse effects Just don t believe patient Friedman et al. Arch Ophthalmol 2005 ; 123:1134; Quigley et al. Ophthalmology 2007; 114:

10 GAPS: FACTORS ASSOCIATED WITH NON-ADHERENCE IN MULTIVARIATE ANALYSIS Lack of concern about vision loss from nonadherence Depending exclusively on doctor for education Difficulty taking medications when away from home Medication cost Telephone recall appointment reminders Not acknowledging stinging and burning Being non-white (regardless of affluence/ education), living in SE USA, being younger Receiving samples/ dependence upon samples DETECTING NON-ADHERENCE Videotaped encounters followed by doctor and patient questionnaires and interviews Doctor-patient dialog generally physician centered - Doctor speaks 70% of words - Closed-ended questions designed to elicit yes/no response Failed to identify non-adherence Friedman et al. Ophthalmology 2008; 115:1320 IMPROVING PATIENT ADHERENCE AND PERSISTENCE IMPROVING PATIENT ADHERENCE AND PERSISTENCE Use easy dosing - Monotherapy - Once daily dosing with PGA Ask open ended questions Acknowledge that dosages are going to be missed. Encourage patient to report more accurately in non-confrontational manner Positive support of patient attempts to adhere Don t change therapy based upon 1 bad IOP reading When patient exceeds target range, tell them that you won t change medications unless IOP is also bad at next visit - Motivation to adhere - 80% of time target is reached at next visit without therapy change IMPROVING PATIENT ADHERENCE AND PERSISTENCE Adherence and persistence are greatly associated with poor attendance at office visits and poor understanding of consequences of vision loss from not using medications - Improve patient recall Telephone much better than post cards - Schedule appointments at completion of exam rather than letting patients call in. - Glaucoma information sheets IMPROVING PATIENT ADHERENCE AND PERSISTENCE Patients that understand potential for vision loss adhere and persist better - Glaucoma information sheets Adherence lower for patients that get all of their information about glaucoma from doctor - Enlist network of patients willing to be mentors - Identify web sites and put on list Apps available to remind patient to take dropsrobocalls 10

11 IMPROVING PATIENT ADHERENCE AND PERSISTENCE Improve communications and health beliefs Ask-tell-ask Ask about understanding of glaucoma, future effects of glaucoma, and risks of non-adherence Tell: Provide the missing information, reinforce correct information, clear all misconceptions Ask: confirm the patient s understanding Knowledge about potential vision loss is critical element missed in passive doctor-dependent patients that are poorly adherent OPTIONS FOR DRUG DELIVERY EVOLUTION OF SUSTAINED DELIVERY PLATFORMS DELIVERED INSIDE THE EYE Allergan is currently performing phase 3 clinical trials on its bimatoprost sustainedrelease implant (bimatoprost SR), which is an intracameral depot implant injected into the anterior chamber. Implant comprising a prostamide associated with a biodegradable polymer matrix that releases an amount of a prostamide 11

12 BIMATOPROST SR Phase 2 trials of the implant showed a mean IOP reduction from baseline of 7.2 to 9.5 mm Hg in 75 eyes 4 months after the injection. The fellow eyes received once-daily topical bimatoprost 0.03% and experienced an IOP reduction of 8.4 mm Hg. The implant lowered IOP in 92% of patients at 4 months and 71% at 6 months. There were no serious adverse ocular events, and the most common adverse events were related to the injection procedure. TRAVOPROST SR TRAVOPROST SR TRAVOPROST SR ENV515- phase 2a open-label, 28-day doseranging study of 21 patients yielded 28% IOP lowering at day 25 in one group, which was comparable to once-daily Travatan Z Envisia is planning to advance to a 12-month study to evaluate the long-term IOP lowering of ENV515. PLATFORMS DELIVERED OUTSIDE THE EYE 12

13 HELIOS (FORSIGHT VISION5) HELIOS (FORSIGHT VISION5) Bimatoprost-laden polymer-matrix insert embedded in a compliant ring. The ring is positioned under the upper and lower eyelids and rests on the conjunctiva. It is visible only at the caruncle once it is in place. The ring is designed to be replaced by an optometrist or ophthalmologist every 6 months. HELIOS (FORSIGHT VISION5) In a phase 2 randomized, double-masked controlled study, the Helios with bimatoprost and artificial tears was compared to a placebo insert and timolol 0.5% BID. The bimatoprost insert lowered IOP, but less than did topical timolol 0.5% dosed twice daily in eyes with placebo insert Retention was 90% at 6 mos ForSight Vision5 recently acquired by Allergan Bimatoprost/timolol FC ring in development PUNCTAL DELIVERY SYSTEM OTX-TP Releases travoprost and is visible via fluorescence. May require flushing the canaliculus with saline or other maneuvers if removal is needed. Retention of the OTX-TP device was 91% at 60 days and 48% at 90 days. PUNCTAL DELIVERY SYSTEM 13

14 PUNCTAL DELIVERY SYSTEM Mati Therapeutics device, L-PPDS (latanoprost-punctal plug delivery system), is a drug-eluting punctal plug. L-PPDS releases latanoprost and is grossly visible. As a superficial punctal plug, it can be pulled out relatively easily. GREAT THINGS ABOUT SUSTAINED DELIVERY Compliance is greatly enhanced Potentially fewer issues for patients NOT SO GREAT THINGS ABOUT SUSTAINED DELIVERY Injectable meds and implants- if med doesn t work topically or has adverse effects, drop is stopped; can t easily stop implantable devices. Implants can theoretically block parts of the angle Complications with invasive options - Endophthalmitis Decreased access to care? NOT SO GREAT THINGS ABOUT SUSTAINED DELIVERY Patients still have to verify if plug or ring is still in place May be challenging for some - If patients have to check daily- why not just use a drop? Contact lens-delivery system: - Older patients handling lenses? - Issues with infectious keratitis NOT SO GREAT THINGS ABOUT SUSTAINED DELIVERY Limitations- how many drugs can you load into a ring or put in the anterior chamber? Patients only have 2 puncta per eye- may still need topical therapy as well Drugs may work better in pulsatile form and not so well in constant delivery PGAs less effective at BID dosing- receptor supersaturation and desensitization - Downtime between drops prevents desensitization 14

15 NOT SO GREAT THINGS ABOUT SUSTAINED DELIVERY SR products seem less effective than drops Will insurance pay for it just to increase compliance? ANTI-VEGF MODEL FOR AMD Compared to clinical trials, VA outcomes are worse and there are fewer injections done in the real world. Patients lost to follow-up are likely doing poorly. Drop out rate 20%-30% WILL PATIENTS GO FOR IT? CONCLUSIONS Strong push for sustained drug delivery Several years away Some options will be invasive - Limit access to care Most options will be non-invasive All offer some benefits combined with limitations Drops, SLT, and surgery will not become obsolete Will these options revolutionize glaucoma management? ANGLE CLOSURE GLAUCOMA ANGLE CLOSURE GLAUCOMA A severe type of glaucoma caused by the apposition of the iris to the trabecular meshwork, obstructing the outflow of aqueous, due to forces acting at four successive anatomic levels: the iris (pupillary block), the ciliary body (plateau iris), the lens (phacomorphic glaucoma), and vectors posterior to the lens (malignant glaucoma). 15

16 CURRENT TERMINOLOGY Narrow Angle Glaucoma Primary angle closure suspect Primary angle closure Primary angle closure glaucoma Primary angle closure attack SUSPECT ZAP STUDY Pigmented trabecular meshwork blocked by iris - Extent of blockage not clear No PAS Disc and IOP normal Probe for symptoms of intermittent closure Not clear if LPI or observation is better Pigmented TM is blocked by iris for Have either PAS or elevated IOP No disc damage or field loss Considered pathologic LPI recommended GLAUCOMA Pigmented TM is blocked by iris for Have either PAS or elevated IOP Glaucomatous neuropathy and field loss LPI recommended 16

17 ATTACK Near complete apposition of iris to pigmented TM Classic signs and symptoms - Injection, vision loss, nausea, emesis, halos, corneal edema, elevated IOP, inflammation, mid-dilated fixed pupil Medical therapy, iridotomy, iridoplasty, trabeculectomy - Lens extraction? ANGLE CLOSURE GLAUCOMA Second leading cause of blindness worldwide Vision loss more common in ACG than POAG 7 million blind from glaucoma worldwide - 4 million blind from ACG More malignant By 2020, PACG will affect 20 million people, and 5.3 million will be blind. ANGLE CLOSURE GLAUCOMA: PATIENT PROFILE White > Black - Angle closure is uncommon in patients of African descent Asian: ACG > POAG Females > males Older > younger Hyperopes > myopes Eskimo population has the highest incidence of angle closure CLASSES OF ANGLE CLOSURE Primary angle closure glaucoma (ACG) with pupil block - Acute - Subacute (intermittent) - Chronic Primary angle closure without pupil block - Plateau iris syndrome Secondary angle closure with pupil block Secondary angle closure without pupil block CLASSES OF ANGLE CLOSURE Primary angle closure glaucoma (ACG) with pupil block - Acute - Subacute (intermittent) - Chronic Primary angle closure without pupil block - Plateau iris syndrome Secondary angle closure with pupil block Secondary angle closure without pupil block 17

18 WITH PUPIL BLOCK Irido-lenticular apposition Mid dilated state causes most problems - Pupil block is normal physiology - Some develop a pathological problem Absent egress of aqueous to anterior chamber Pressure buildup Iris bombé: bowing forward of iris due to posterior pressure buildup. Irido-corneal apposition Closure of angle Pupil block mechanism Narrow angle GONIOSCOPY 18

19 WITH PUPIL BLOCK Permanent synechial closure if contact remains too long Miosis has long been the standard to pull the iris out of the angle, but anything that alleviates the irido-lenticular apposition will benefit. -Very few doctors will dilate a patient in angle closure -Atropine may be a medication of choice in some cases WITH PUPIL BLOCK IOP rise (40-70 mm hg or higher) -Possible vascular occlusion due to elevated IOP Peripheral anterior synechiae (PAS) formation -Permanent WITH PUPIL BLOCK Anatomic features: Small corneal diameter Small axial length Axial length 5% shorter Moderate hyperopia Thick lens 7% thicker Greater propensity for lens to move forward WITH PUPIL BLOCK - Shallow anterior chamber AC depth > 2.5 mm-almost never see ACG AC depth mm-sometimes see ACG AC depth < 2.0 mm-frequently see ACG 75% of ACG has AC depth < 1.5 mm -Anterior chamber 24% shallower than controls -Anterior chamber volume 37% less than controls 19

20 GLAUCOMA: CLASSES Acute Subacute Chronic ACUTE GLAUCOMA: SYMPTOMS Red eye Photophobic Halos- corneal edema Blurred vision Nausea/emesis ACUTE GLAUCOMA: SIGNS Elevated IOP Mid-dilated pupil Mild anterior chamber reaction Cloudy, corneal edema Glaukomflecken ACUTE GLAUCOMA: ACUTE Entire angle involved Vision loss in days Profound si/sx IOP 45 mm Hg (or greater) common Corneal edema PAS forms quickly - May result in chronic IOP elevation after breaking attack and curing angle closure due to TM damage. ACUTE GLAUCOMA: MANAGEMENT Beta blocker (i gtt, no more than 2 drops) Pilocarpine 2% (if IOP < 40 mm hg). Be sure that your diagnosis is correct before you start pouring pilocarpine into the patient s eye This is becoming a dangerous strategy because too many doctors have a knee-jerk reaction to elevated IOP and pour in the pilocarpine when the diagnosis isn t even angle closure. Concentrations greater than 2% should be avoided as it may increase ciliary body congestion and lead to greater pupil block 20

21 ACUTE GLAUCOMA: MANAGEMENT Iopidine vs Alphagan Pred forte q15 min. PGA works too slow CAI - Diamox 500 mg - Topical may be used if oral not available or contraindicated. Oral osmotics ACUTE GLAUCOMA: MANAGEMENT Laser PI Argon laser iridoplasty Trabeculectomy and tubes Iridotomy or trabeculectomy - High incidence of flat chambers after trab - Iris and lens move forward Phaco lens removal - After attack broken 21

22 GLAUCOMA: SUBACUTE Recurrent attacks Subsides spontaneously - Opens during sleep with miosis Lesser symptoms - Episodic blurred vision & halos Partial angle closure - PAS, particularly superiorly Cataract Incorrectly called narrow angle glaucoma - Angle chronically narrow Incorrectly confused with NTG or POAG- do gonio PRIMARY SUBACUTE ANGLE CLOSURE GLAUCOMA: MANAGEMENT Laser PI or lens removal Long term medical management alone not appropriate - False security-allows PAS to form Trab or tube surgery - Again, risk of malignant glaucoma 59 YEAR OLD ASYMPTOMATIC WHITE FEMALE Presents with complaints of mildly blurred vision, mild discomfort in both eyes BVA: OD 20/20, OS 20/20 38 mm Hg OD, 42 mm Hg OS Slit lamp: extremely narrow angles OU - Gonioscopy: Bare TM noted inferiorly only OU GLAUCOMA: CHRONIC Most common form of primary angle closure glaucoma - 80% of PACG is chronic, 20% acute Asymptomatic PAS - zippering shut of angle, especially superior angle Discovered on routine exam Mistaken for POAG- do gonio GLAUCOMA: CHRONIC Multimechanism: The pattern of angle closure appears to mainly be creeping closure. Pupillary block: caused by iris bombé due to pupillary block with acute or subacute attack. Non-pupillary blocking: usually have a deeper anterior chamber, and tend to be younger (below 40 years of age). Angle closure in this form of chronic ACG is caused by: iris crowding mechanism or/and anteriorly positioned ciliary body against iris root to angle. GLAUCOMA: CHRONIC Iridotomy first, then filtering surgery if not controlled Often will require topical medications following iridotomy to control IOP Stable visual fields and good long term IOP control were seen in 90% of chronic primary angle closure glaucoma eyes on medical/surgical therapy Lensectomy is being investigated as a primary treatment for chronic angle closure glaucoma and may become the preferred treatment. Currently a very viable option. - The role of clear lensectomy (i.e. extraction of the non-cataractous lens) in patients with PCACG is unclear. The Effectiveness in Angle Closure Glaucoma of Lens Extraction (EAGLE) study, a prospective, randomized clinical trial now underway, will compare the safety and effectiveness of LPI and medical therapy to clear lens extraction for patients with newly diagnosed PCACG. 22

23 EAGLE STUDY Removal of clear lenses in eyes with PACG with IOP > 21 mm or eyes with PAC (without glaucoma) and IOP > 30 mm. Findings included: Patients undergoing phaco lens extraction had far fewer IOP controlling meds Only 1 patient needed trabeculectomy after phaco whereas 24 patients in the LPI group needed trabeculectomy Far fewer meds after phaco than LPI Azuara-Blanco A, Burr JM, Cochran C, et al. Effectiveness in Angle-closure Glaucoma of Lens Extraction (EAGLE) Study Group. The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE):The Lancet. Volume 388, No , p , 1 October SURGICAL TREATMENT FOR PACG Phaco-goniosynecialysis - Lens is removed and PAS is surgically cut open May be as effective as traditional glaucoma surgery (trabeculectomy) but with fewer complications. Avoids malignant glaucoma Attempts to restore function to a previously closed angle Factors determining whether or not PAS release will lower IOP include duration of angle closure, extent of PAS, function of proximal and distal outflow pathways prior to closure, secondary functional changes to trabecular meshwork and Schlemm s canal following closure - Theoretically goniosynechialysis makes sense, but few actually perform the procedure BRAIN TEASER Can you dilate a patient with chronic angle closure? CASE Patient with CACG undergoes LPI successfully Angles open to scleral spur OU IOP drops to 19 mm Hg w/o meds At 3 mos F/U IOP 27 mm Hg OU At 6 mos F/U IOP 35 mm Hg OU What s happening here? CLINICAL PEARL: After successful laser treatment for angle closure glaucoma, the IOP may still be elevated. The cause typically is compromise (damage) to the angle structures (meshwork) from the angle closure. Many doctors don t realize this and use the term; mixed mechanism glaucoma to denote a case where the patient has been successfully treated with laser for angle closure, yet still has elevated IOP. The doctor who uses the term, mixed mechanism glaucoma is really saying, The pressure is high and I don t know why. 23

24 GLAUCOMA: PROPHYLAXIS Laser PI - Especially if AC < 2.0 mm Gonio to identify areas of reversible closure Gonio is actually poor predictor of risk of ACG - Static view of dynamic phenomenon 10 people have small eyes 1 will develop ACG - Factors other than small size involved Choriodal expansion Iridotomy speeds cataract CLASSES OF ANGLE CLOSURE Primary angle closure glaucoma (ACG) with pupil block - Acute - Subacute (intermittent) - Chronic Primary angle closure without pupil block - Plateau iris syndrome Secondary angle closure with pupil block Secondary angle closure without pupil block WITHOUT PUPIL BLOCK Plateau iris - Gonioscopic description of any eye with deep anterior chamber and narrow angle due to large last role of the iris Laser PI - Occasionally helps, but mechanism unknown Argon laser iridoplasty Affected by dilation-crowds angle Permanent PAS may form Plateau iris (primary angle closure without pupil block) 24

25 Peripheral roll of the iris, seen on indentation gonioscopy. Some consider this pathognomonic. CLASSES OF ANGLE CLOSURE Primary angle closure glaucoma (ACG) with pupil block - Acute - Subacute (intermittent) - Chronic Primary angle closure without pupil block - Plateau iris syndrome Secondary angle closure with pupil block Secondary angle closure without pupil block SECONDARY ANGLE CLOSURE WITH PUPIL BLOCK Uveitic Phacomorphic Aphakia Vitreous prolapse Pseudophakia Reverse pupil block with AC lens Subluxated lens 25

26 CLASSES OF ANGLE CLOSURE Primary angle closure glaucoma (ACG) with pupil block Acute Subacute (intermittent) Chronic Primary angle closure without pupil block Plateau iris syndrome Secondary angle closure with pupil block Secondary angle closure without pupil block SECONDARY ANGLE CLOSURE WITHOUT PUPIL BLOCK Either the peripheral iris is pulled or pushed into the cornea. - Drug induced choroidal expansion - Neovascular glaucoma - Neoplastic disease - Some inflammatory cases/ uveitic - Ciliary block CILIARY BLOCK GLAUCOMA Also known as malignant glaucoma and aqueous misdirection syndrome Anterior displacement of the iris and ciliary body Due in part to swelling of the ciliary body, annular detachment of the ciliary body, and anterior vitreous displacement. Disparity in AC depth between eyes Miotics will aggravate, or even cause this condition No benefit from iridotomy CILIARY BLOCK GLAUCOMA Frequently caused by misdirection of aqueous into the vitreous and posterior chamber with anterior displacement of structures of the eye. Abnormally impermeable vitreous face. This most typically occurs following ocular surgery for angle closure glaucoma. Can occur immediately post-op or much later. Unresponsive to conventional medical and surgical glaucoma therapies 26

27 CILIARY BLOCK GLAUCOMA Best managed with atropine 1% BID, phenylephrine 10% BID, and acetazolamide 1 gm PO QD. Eventually, everything but atropine is tapered (atropine is continued indefinitely). Surgical options: - Vitrectomy and lensectomy - Nd:YAG disruption of capsule WHAT S WRONG WITH YOUR EYE? BVA is 20/15 OD, OS. Confrontation fields and EOM s are normal and her pupils react to light without afferent defect. IOP is 15 mm Hg OU and discs are 0.4/0.4 However, the right pupil is misshapen ICE SYNDROMES Iridocorneal endothelial syndromes (ICE): syndromes where corneal endothelial cells over-secrete leading to Descemet s membrane migrating and extending over the trabecular meshwork. As this membrane contracts, PAS forms. Theses are typically unilateral and more commonly affect women. ICE SYNDROMES Essential iris atrophy- gonioscopy shows progressive angle closure by PAS. The pupil is displaced towards the PAS and the iris shows mildto-moderate ectropion uveae, stromal atrophy, and full thickness iris hole formation opposite the PAS 27

28 ICE SYNDROMES ICE SYNDROMES Chandler s syndrome- changes in the iris are mild to absent while corneal edema presents at normal IOP level Iris nevus (Cogan-Reese) syndrome- the angle changes are the same as in essential iris atrophy, except that an iris nevus covers the anterior iris ICE SYNDROMES Treatments include filtering surgery and often penetrating keratectomy. Medical therapy tends to work for a short while and LTP is ineffective Frankly may never develop glaucoma ANGLE CLOSURE GLAUCOMA REVISITED ACG angle opens less dynamically in response to light and pilocarpine Patients of Chinese descent 5 fold more ACG, yet incidence of small eyes not 5 fold Factors other than small eye size must contribute to ACG The factor appears to be the choroid Choroidal expansion seen on UBM in some cases of ACG ACG: ROLE OF THE CHOROID Choroid expansion likely contributes heavily to ACG Choroidal expansion takes up volume Choroidal expansion by 20% takes up 96 ul - Normal anterior chamber is only 100 ul - IOP from 20 mm Hg to 60 mm Hg instantaneously ACG: ROLE OF THE CHOROID Choroidal expansion leads to forward movement of lens and iris and chamber flattening with ACG Change in choroidal vessel permeability leads to choroidal expansion - Proteins, fluid, blood moves into extracellular/ extravascular space in choroid 28

29 FACTORS AFFECTING CHOROID Associated with ACG in otherwise normal eyes: - Hypotony Choroidal detachment - Carotid Cavernous Sinus Fistula - Suprachoroidal hemorrhage - Scleritis - Choroidal tumors - PRP - Drug-induced choroidal effusions (sulfa based) Ciliary Effusion Anterior Rotation of the Ciliary Body - Reduces tension on the zonules Lens Thickening Induces myopia - Iris-Lens diaphragm shifts anteriorly Induces myopia by changing effectivity - Shallowing of Anterior Chamber Potential for angle closure NASAL TEMPORAL CASE DRUGS CAUSING ACG Acetazolamide Hydrochlorothiazid e Trimethoprimsulfamethoxazole Indapamide Promethazine Spironolactone Isosorbide dinitrate Viagra Bromocriptine Tetracycline Corticosteroids Penicillamine Quinine Metronidazole Isotretinoin Aspirin Topiramate* 39 YOF Recently started on Topamax for migraine Sudden onset blurred vision and eye pain Formerly emmetropic, now (-) 4.00 DS IOP 39 mm hg D/C Topamax; add PF Q1H, scopolamine BID, beta blocker BID 29

30 CHOROIDAL INVOLVEMENT IN ACG Initial Presentation Drug-induced choroidal expansion Choroidal expansion in ACG associated with shallowing of chamber Malignant glaucoma may not be aqueous misdirection, but poor fluid permeability and choroidal expansion Atropine may work by moving ciliary body and improving forward diffusional area for fluid - Atropine may be a better choice than pilocarpine Resolution CASE: THE FIST AND THE EYE 75 YOAM: medical hx unremarkable (+) Pseudophakia OS Previously examined and fine Struck accidentally by grandchild Presents 2 weeks later: (+) pain/photophobia/lacrimation/redness IOP 35 mm OS (17 mm hg OD) See slide: CASE: THE FIST AND THE EYE Diagnosis: vitreous prolapse with pupil block and secondary angle closure Management: - Tropicamide 1%, phenylephrine 2.5% - 30 minutes: Angle opens Chamber deepens IOP 22 mm Hg - Plan: Homatropine 5%, PF, beta blocker, LPI Clinical Pearl: Many cases of angle closure, such as aphakic (vitreous) pupil block, can be best managed by dilating the patient. Knowing whether to dilate or miose an angle closure separates doctors from technicians. 30

31 POAG AND PRIMARY ANGLE CLOSURE GLAUCOMA Changing angle configuration-miotics and age Gonio on a yearly basis on all POAG patients to determine if a conversion from open to closed angle is occurring. Laser PI for occludable angles Narrow angle glaucoma is an antiquated term. Better to speak in terms of chronic angle closure, etc. PERSISTENT ANGLE CLOSURE AFTER LPI Not pupil block mechanism - Choroidal effusion, plateau iris, etc Significant PAS LPI not complete/ patent 31