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Canine Glaucoma: Medical and Surgical Treatment Options*

Canine Glaucoma: Medical and Surgical Treatment Options*

3 CE CREDITS CE Article 2

Author Shelby L. Reinstein, DVM, MS, with Beasley at The University of Pennsylvania. Photograph by Holly Palin Canine : Medical and Surgical Treatment Options*

❯❯ Shelby L. Reinstein, Abstract: Canine glaucoma can be treated medically or surgically, depending on the underlying DVM, MS cause, disease stage, desired outcome, available equipment, and owner’s financial limitations. The University of Pennsylvania Common medications for glaucoma include hyperosmotics, β-blockers, carbonic anhydrase in- ❯❯ Amy J. Rankin, DVM, hibitors, , and analogues. Surgical options include aqueous humor MS, DACVO shunts, cyclodestructive procedures, enucleation, intrascleral prostheses, and chemical ablation. ❯❯ Rachel Allbaugh, DVM, Each patient requires a customized treatment plan that generally includes a combination of medi- MS, DACVO cations and, potentially, surgical intervention. Kansas State University

he goals of glaucoma therapy are to via β- blockade in the ciliary preserve or regain vision by main- body. 2 A large in dogs demon- Ttaining normal intraocular pressure strated that predisposed eyes treated topi- (IOP) and to alleviate pain. The therapeutic cally with 0.5% twice daily as a plan depends on the patient’s visual status, prophylactic glaucoma therapy developed the chronicity of the condition, and the glaucoma much later than nontreated eyes.3 underlying cause (primary or secondary). maleate is a nonselective β antag- Congenital glaucoma is rare and cannot be onist. Topical administration of timolol causes At a Glance treated well. mild in dogs and may increase aque- ous humor outflow in addition to inhibiting Antiglaucoma Medications Antiglaucoma Medications production.3,4 Page 454 Medications for glaucoma either decrease Both β1-selective and nonselective β Surgery for Glaucoma aqueous humor production or increase aque- antagonists may have undesirable car- Page 456 ous humor outflow. There is no single opti- diac effects, including , syn- mal therapeutic protocol for all dogs with cope, or reduced myocardial contractility.

glaucoma, and many patients require mul- Additionally, blockade of β2 receptors by tiple medications. Studies of antiglaucoma nonselective β blockers could produce medications show that dogs with glaucoma adverse respiratory effects, especially in demonstrate a greater decline in IOP than patients with , so timolol should not do dogs with a normal IOP.1 Table 1 gives be used in dogs with cardiac or pulmonary an overview of antiglaucoma medications. disease.3

Medications to Decrease Aqueous Carbonic Anhydrase Inhibitors Humor Production Systemic and topical carbonic anhydrase β Blockers inhibitors (CAIs) are available. Inhibition *A companion article, “Canine Glaucoma: Pathophysiology and Betaxolol is a selective β1 antagonist that of carbonic anhydrase decreases aqueous Diagnosis,” begins on page 450. decreases the production of aqueous humor humor production by reducing the syn-

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table 1 Antiglaucoma Medications1,8,a,b

Recommended Drug Available Preparations Dose or Timing Contraindications

β Blockers Betaxolol 0.25% and 0.5% solutions Keratoconjunctivitis sicca, cardiac or q12h Timolol maleate 0.25% and 0.5% solutions respiratory disease Carbonic anhydrase inhibitors

Methazolamide 25- and 50-mg tablets 2.5–5 mg/kg Hypokalemia, metabolic acidosis q8–12h PO

Brinzolamide 1% solution None, but may cause irritation shortly after instillation q8h 2% solution None, but may cause irritation shortly after instillation

Dorzolamide–timolol maleate 2% dorzolamide and 0.5% timolol maleate q12h Keratoconjunctivitis sicca, cardiac or respiratory disease Cholinergics 1% solution q8–12h Anterior lens luxation, uveitis Demecarium bromidec 0.125% and 0.25% solutions q12–24h Prostaglandin analogues 0.005% solution 0.004% solution q12–24h Severe uveitis, anterior lens luxation

Bimatoprost 0.03% solution Hyperosmotic agents Mannitol 20% solution 1–1.5 g/kg IV Cardiac or renal disease, dehydration slowly over 20 min

Glycerin 50% and 75% solutions 1–2 g/kg PO Cardiac or renal disease, mellitus, dehydration

aWillis AM, Diehl KA, Robbin TE. Advances in topical glaucoma therapy. Vet Ophthalmol 2002;5(1):9-17. bMedications are topical ophthalmic preparations unless otherwise noted. cMust be compounded. thesis of bicarbonate in the .1,2 fewer systemic effects. No additional decline The oral CAIs and meth- in IOP is obtained from the combination of azolamide can have systemic adverse effects. an oral CAI with a topical CAI; therefore, Acetazolamide is no longer recommended due we recommend the use of a topical CAI for to the high incidence of such effects. Adverse long-term management.6,7 The most common effects associated with the use of methazol- adverse effect of topical dorzolamide is tran- amide include gastrointestinal upset, meta- sient blepharospasm after instillation.7,8 bolic acidosis, and hypokalemia.5 A solution of 2% dorzolamide and 0.5% Topical CAIs reach adequate ciliary body timolol maleate is available. This combina- concentrations and have a lower risk of sys- tion therapy is as efficacious in reducing IOP temic adverse effects. signifi- as concurrent use of each drug,9 but the com- cantly reduces IOP in dogs with glaucoma.1 mercially available combination improves client Dorzolamide has been shown to reduce IOP compliance because it requires only twice-daily as effectively as with many administration.8,9

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Other Medications an effect on the conventional outflow pathway as 1,13 α2 Agonists and epinephrine have historically well. These drugs may also cause a reduction in been used to treat glaucoma, but with recent aqueous humor production.14 Prostaglandin ana- advances in glaucoma therapy, other drugs logues should be avoided in cases of glaucoma with increased efficacy and fewer potential secondary to anterior lens luxation or uveitis.

adverse effects (β blockers, CAIs) may be Latanoprost is a selective prostaglandin F2α recep- more appropriate.8,10,11 tor agonist that results in a dramatic decrease in IOP within 20 minutes.15 Travoprost and bimato- Medications to Increase Aqueous prost are newer prostaglandin analogues shown Humor Outflow to be efficacious in dogs.1 Agents Parasympathomimetics are used in the treat­- Hyperosmotic Agents ment of c a n i ne g laucom a except when i nt r ao c u la r Hyperosmotic agents reduce the production inflammation is present. Parasympa­thomimetics of aqueous humor by reducing plasma flow are used in long-term management of canine through the ciliary body, thereby dehydrating glaucoma and are often combined with CAIs the vitreous.5 The main indication for the use and/or β blockers to improve IOP control.1 They of hyperosmotic agents in canine glaucoma is induce contraction of the ciliary body muscu- emergency management of increased IOP. For lature and severe miosis, which subsequently maximum efficacy, water should be withheld opens the drainage angle, facilitating aqueous for 4 hours after administration. humor outflow. Parasympathomimetics are con- Mannitol is an osmotic that has traindicated in dogs with anterior lens luxation been shown to significantly reduce IOP within QuickNotes and anterior uveitis. 15 minutes of administration and can remain Pilocarpine is a direct-acting parasympa­ effective for 6 to 10 hours.16 Mannitol can be Many patients thomimetic that simulates the action of acetyl- used safely in most dogs but should not be with glaucoma on the iris and ciliary body.2 Because used in dogs with cardiac or renal disease or require multiple of the nonphysiologic pH of the solution, topi- in dehydrated patients. medications. cal administration causes irritation in most Oral glycerin causes a significant decrease dogs; therefore, this drug is not generally rec- in IOP within 30 minutes of administration ommended as a first-line therapy.1,5 and has a duration of effect of 10 hours.16 is an indirect-acting Glycerin should not be used in dogs with dia- parasympathomimetic that increases the dura- betes mellitus. The most common side effect tion of the normally produced in of oral administration is gastrointestinal upset. the ciliary body. The main advantage of deme- In an emergency situation, we recommend carium bromide is its long duration of action. starting with a topical . Demecarium bromide 0.25% has been shown to The IOP should be rechecked after 20 to significantly delay the onset of primary glaucoma 30 minutes. If it is still elevated, an osmotic in predisposed eyes when used in combination diuretic may be indicated. After application with a topical steroid.3 Demecarium bromide of a topical prostaglandin analogue, a topical 0.125% and 0.25% are available from compound- CAI can be administered to gain further con- ing pharmacies. Topical demecarium bromide trol of the IOP. If not contraindicated, a topical can reach systemic concentrations high enough β blocker can also be administered. to result in toxicosis. Although this adverse effect is uncommon, the drug should be used with Surgery for Glaucoma caution in small dogs.12 Signs of toxicosis include When medical therapy can no longer control diarrhea, salivation, and vomiting.2 the IOP, surgery may be indicated. The time for which medical therapy is effective depends Prostaglandin Analogues on the individual patient. If the IOP becomes Prostaglandin analogues are the newest topical uncontrollable or the dog is uncomfortable, glaucoma drugs used in dogs. They are thought to early referral to a veterinary ophthalmologist lower IOP primarily by increasing uveoscleral out- for surgical management is ideal. Some surgical flow of aqueous humor via their action on iris and procedures that can alleviate pain associated ciliary body musculature; however, research shows with end-stage glaucoma in nonvisual eyes

456 Compendium: Continuing Education for Veterinarians® | October 2009 | CompendiumVet.com FREE Canine Glaucoma: Treatment Options CE can be performed by a general practitioner. ECPC had controlled IOPs at 1 year and 77% As with medical therapy, surgical procedures retained vision at 1 year.a to address glaucoma either reduce aqueous humor production or improve aqueous humor Surgery to Increase Aqueous outflow. The procedure chosen depends on Humor Outflow the dog’s visual status and the desired cosmetic Currently, gonioimplants and the Cullen frontal outcome. Medical therapy is usually still neces- sinus shunt are the most commonly used shunts sary after procedures that preserve vision. in veterinary ophthalmology. Gonioimplants consist of an i mplant and t ubi ng t hat allows aque- Surgery to Decrease Aqueous ous humor to drain from the anterior chamber Humor Production into the subconjunctival space. Gonioimplants Cyclodestruction, or destruction of the cili- can be combined with surgical techniques to ary body, decreases the production of aque- decrease aqueous humor production but usu- ous humor and can be performed using ally do not suffice for sole long-term manage- cryotherapy, transscleral lasers, or endoscopic ment. The Cullen frontal sinus shunt is a valved cyclophotocoagulation. tube that is anchored into the frontal sinus Cyclocryotherapy uses either liquid nitro- and directed into the anterior chamber of the gen or nitrous oxide applied to the sclera by a eye.21,22 Complications of shunting procedures probe to cause cryonecrosis of the ciliary body. include occlusion of the tube with fibrin, fibro- Cryotherapy can cause severe uveitis, cataracts, sis around the implant, extrusion of the implant, and retinal detachment and is therefore not and postoperative hypotony.1,22,23 generally recommended in visual eyes.1 Transscleral cyclophotocoagulation (TSCP) Salvage Procedures QuickNotes uses a diode or Nd:YAG laser to irradiate the Chronic end-stage glaucoma may be painful, ciliary body. Studies have shown this proce- and buphthalmic globes are predisposed to As with medical ther- dure to be effective in controlling IOP.17,18 The exposure keratitis. Surgical options for chroni- apy, surgical pro- most common complications of TSCP are cally glaucomatous globes include enucleation, cedures to address recurrence of glaucoma requiring a second evisceration with intrascleral prosthesis, and glaucoma either procedure, secondary cataract formation, and chemical ablation. reduce aqueous 19 ulcerative keratitis. This procedure may be humor production combined with implantation of an anterior Enucleation chamber shunt (gonioimplant) for better con- Enucleation is relatively inexpensive and has or improve aqueous trol of postoperative IOP spikes. Two studies few complications. An orbital prosthesis may be humor outflow. have shown the combination procedure to be placed to improve the cosmetic appearance. The successful, with up to 58% of dogs retaining main disadvantage of enucleation is the postop- vision after 1 year.18,20 erative appearance of the patient. The benefits One of the main disadvantages of the non- include the potential for histopathologic exami- invasive cyclodestructive techniques is the nation of the globe and immediate pain control.1 inability to see the extent of destruction of the ciliary body. Endoscopic cyclophotocoagu- Intrascleral Prosthesis lation (ECPC; endolaser) uses a diode endo- Evisceration and intraocular placement of a scopic laser to deliver energy to the ciliary silicone ball has a 95% success rate and, often, body. Most patients require phacoemulsifica- very good cosmetic results. Postoperative com- tion and intraocular lens implantation before plications are minimal but may include corneal the procedure to prevent cataract formation. ulcers and persistent corneal edema.1,23 Other reported complications include uncon- trolled IOP, corneal ulceration, retinal detach- Chemical Ablation ment, and hyphema secondary to postoperative Pharmacologic destruction of the ciliary body hypotony. This procedure offers a high success is accomplished by injecting gentamicin and rate of IOP control and vision preservation and dexamethasone into the vitreous cavity. Com­ may allow a decrease in antiglaucoma medica- plications include inadequate control of IOP, tions. In a study of 106 dogs with primary and aPersonal communication, D. Bras, DVM, MS, DACVO, secondary glaucoma, 93% of dogs treated with MedVet, Worthington, OH, February 5, 2008.

CompendiumVet.com | October 2009 | Compendium: Continuing Education for Veterinarians® 457 FREE CE Canine Glaucoma: Treatment Options hyphema, uveitis, retinal detachment, cataract develop- ment, and phthisis bulbi.23

Conclusion Canine glaucoma is difficult to manage, but there are many therapeutic options. Owner expectations, visual sta- tus, and cause of the disease help dictate the appropriate treatment course.

References 1. Gelatt KN, Brooks DE, Kallberg ME. The canine . In: Gelatt KN, ed. Vet- erinary Ophthalmology. 4th ed. Ames, Iowa: Blackwell Publishing; 2007:753-811. 2. Bartlett J, Jaanus S. Clinical Ocular Pharmacology. 2nd ed. Stoneham, MA: But- terworth Publishers; 1989:929. 3. Miller PE, Schmidt GM, Vainisi SJ, et al. The efficacy of topical prophylactic an- tiglaucoma therapy in primary closed angle glaucoma in dogs: a multicenter clinical trial. JAAHA 2000;36(5):431-438. 4. Wilkie DA, Latimer CA. Effects of topical administration of timolol maleate on intraocular pressure and pupil size in dogs. Am J Vet Res 1991;52(3):432-435. 5. Derick RJ, Craig EL, Weber PA. Glaucoma therapy. In: Mauger TF, Craig EL, eds. Havener’s Ocular Pharmacology. 6th ed. St. Louis: Mosby; 1994:172-200. 6. Cawrse MA, Ward DA, Hendrix DV. Effects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs. Am J Vet Res 2001;62(6):859-863. 7. Gelatt KN, MacKay EO. Changes in intraocular pressure associated with topi- cal dorzolamide and oral methazolamide in glaucomatous dogs. Vet Ophthalmol 2001;4(1):61-67. 8. Willis AM. Ocular hypotensive drugs. Vet Clin North Am Small Anim Pract 2004;34(3):755-776. 9. Plummer CE, MacKay EO, Gelatt KN. Comparison of the effects of topical admin- istration of a fixed combination of dorzolamide-timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs. Vet Ophthal- mol 2006;9(4):245-249. 10. Robin AL. Short-term effects of unilateral 1% therapy. Arch Oph- thalmol 1988;106(7):912-915. 11. Toris CB, Tafoya ME, Camras CB, Yablonski ME. Effects of apraclonidine on aqueous humor dynamics in human eyes. Ophthalmology 1995;102(3):456-461. 12. Ward DA, Abney K, Oliver JW. The effects of topical ocular application of 0.25% demecarium bromide on serum levels in normal dogs. Vet Oph- thalmol 2003;6(1):23-25. 13. Richter M, Krauss AH-P, Woodward D, Lutjen-Drecoll E. Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglan- din agonists and a prostamide. Invest Ophthalmol Vis Sci 2003;44(10):4419-4426. 14. Ward DA. Effects of latanoprost on aqueous humor flow rate in normal dogs. Proc 36th Annu Meet Am Coll Vet Ophthalmologists 2005:15. 15. Studer ME, Martin CL, Stiles J. Effects of 0.005% latanoprost solution on in- traocular pressure in healthy dogs and cats. Am J Vet Res 2000;61(10):1220-1224. 16. Lorimer DW, Hakanson NE, Pion PD, Merideth RE. The effect of intravenous man- nitol or oral glycerol on intraocular pressure in dogs. Cornell Vet 1989;79(3):249-258. 17. Nasisse MP, Davidson MG, English RV, et al. Treatment of glaucoma by use of transscleral neodymium:yttrium aluminum garnet laser cyclocoagulation in dogs. JAVMA 1990;197(3):350-354. 18. Sapienza JS, van der Woerdt A. Combined transscleral diode laser cyclophoto- coagulation and Ahmed gonioimplantation in dogs with primary glaucoma: 51 cases (1996-2004). Vet Ophthalmol 2005;8(2):121-127. 19. Hardman C, Stanley RG. Diode laser transscleral cyclophotocoagulation for the treatment of primary glaucoma in 18 dogs: a retrospective study. Vet Ophthalmol 2001;4(3):209-215. 20. Bentley E, Miller PE, Murphy CJ, Schoster JV. Combined cycloablation and gonio- implantation for treatment of glaucoma in dogs: 18 cases (1992-1998). JAVMA 1999;215(10):1469-1472. 21. Cullen CL, Allen AL, Grahn BH. Anterior chamber to frontal sinus shunt for the diversion of aqueous humor: a pilot study in four normal dogs. Vet Ophthalmol 1998;1(1):31-39. 22. Cullen CL. Cullen frontal sinus valved glaucoma shunt: preliminary findings in dogs with primary glaucoma. Vet Ophthalmol 2004;7(5):311-318. 23. Cook CS. Surgery for glaucoma. Vet Clin North Am Small Anim Pract 1997; 27(5):1109-1129.

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3 CE CREDITS CE Test 2 This article qualifies for 3 contact hours of continuing education credit from the Auburn University College of Veterinary Medicine. Subscribers may take individual CE tests online and get real-time scores at CompendiumVet.com. Those who wish to apply this credit to fulfill state relicensure requirements should consult their respective state authorities regarding the applicability of this program.

1. The goal of therapy for canine glaucoma 5. Which statement regarding parasym- 8. Surgical treatment of canine glaucoma is to pathomimetics is true? a. should not be performed in visual a. preserve or regain vision in the eye. a. Parasympathomimetics are contrain- eyes. b. maintain normal IOP. dicated for use in patients with uveitis b. can alleviate pain associated with c. alleviate pain. or anterior lens luxation. end-stage glaucoma in blind eyes. d. all of the above b. Parasympathomimetics lower IOP by c. can decrease the production or inducing mydriasis, therefore opening increase the outflow of aqueous 2. The treatment of glaucoma should aim to the iridocorneal angle. humor, depending on the technique ______the production and/or ______c. Pilocarpine is generally well tolerated chosen. the outflow of aqueous humor. by most dogs. d. b and c a. increase; increase d. The main advantage of demecarium b. decrease; increase bromide is its short duration of 9. Which statement regarding cyclode- c. decrease; decrease action. structive techniques is true? d. increase; decrease a. Destruction of the ciliary body can 6. Which statement regarding prostaglan- be accomplished using cryotherapy, 3. Which statement regarding topical β din analogues is true? transscleral lasers, or endoscopic blockers is true? a. They are thought to increase uveo- cyclophotocoagulation. a. Betaxolol is a nonselective β antagonist. scleral outflow of aqueous humor. b. Cyclocryotherapy has few compli- b. Timolol maleate is a selective β1 b. They may decrease IOP by reducing cations and is thus considered a antagonist. the production of aqueous humor. safe procedure for all patients with c. β Blockers decrease the production c. They are contraindicated for use in glaucoma. of aqueous humor via β-adrenergic patients with uveitis or anterior lens c. Transscleral cyclophotocoagulation blockade in the cornea. luxation. may induce cataract formation. d. Blockers are contraindicated in patients β d. all of the above d. a and c with cardiac or respiratory disease.

4. Which statement regarding CAIs is true? 7. Which statement regarding hyperos- 10. Which statement regarding salvage motic agents is true? surgical procedures for glaucoma is a. Brinzolamide and dorzolamide are topi- true? cal medications that reduce systemic a. Hyperosmotic agents reduce the for- side effects while achieving adequate mation of aqueous humor by increas- a. Enucleation is relatively inexpensive ocular concentrations. ing plasma flow through the ciliary and has few complications. b. CAIs increase the production of aque- body. b. Evisceration and placement of an ous humor by reducing synthesis of b. Hyperosmotic agents are indicated for intrascleral prosthesis improves the bicarbonate in the ciliary body. long-term control of glaucoma. cosmetic appearance. c. Common side effects of oral CAIs c. Mannitol decreases IOP within 15 c. Complications of chemical ablation include gastrointestinal upset, meta- minutes of administration, but its of the ciliary body include inadequate bolic alkalosis, and hyperkalemia. effect only persists for approximately control of IOP, hyphema, uveitis, reti- d. Of the oral CAIs, acetazolamide is pre- 1 hour. nal detachment, cataract formation, ferred to methazolamide because it is d. Oral glycerin is contraindicated in dia- and phthisis bulbi. associated with fewer adverse effects. betic patients. d. all of the above

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