Eyeworld

EW FEATURE 94 be an issue in the near future, there's no reason to leave it behind. "I would say that it's rare that we leave the lens," he said. Dr. Holland also finds that the combination procedure tends to be an easier one in terms of performing the DSEK portion. "In the vast ma- jority of cases there's no advantage to leaving the lens," he said. "The procedure is actually technically harder in the phakic eye because there is less space." Dr. Francis Price said economics are an important advantage favoring the combined approach. "The biggest advantage is decreased cost and convenience to the patient with one surgery instead of two," he said. "In DSEK I don't think that we've seen any difference in outcomes." On the flip side of the coin, however, he finds that for the begin- ning surgeon, doing the procedure in stages is probably easier. "When you do the cataract surgery first and you wait for a month or more, the lens implant has time to fibrose or basically become fixated in the cap- sule," he said. "The capsule shrink wraps around the lens implant; it tightens itself with the zonules, so when you go to put your graft in, you're less likely to dislodge the im- plant." Dr. Price finds that the whole di- aphragm of the lens capsule is stiffer after being in place for a while. "It moves some but not as much as when you do a combined cataract procedure," he said. "When you put air in an eye that you've done a cataract procedure on at the same time, the implant goes back poste- rior quite a bit more than it does if it has been a month or 2 out." With the combined procedure there is more give to the zonules because the capsule hasn't shrunk down at that point. Blue ribbon technique Effectively performing the procedure involves a few different steps, Dr. Holland finds. "At the outset of the procedure surgeons have to figure out what size DSEK they want to do—typically it's in the 8- to 9-mm range," he said. "They measure the cornea and estimate the size, so that's an extra step." In addition to the standard cataract paracentesis, Dr. Holland makes another one. "I like at least two to manipulate the EK button," he said. The only other extra step is to make a 4.5-mm incision instead of a typical 2.2- to 2.4-mm incision for standard phacoemulsification. Dr. Holland marks the 4.5-mm length but initially performs the pha- coemulsification procedure through the typical 2.2-mm incision. "We take the cataract out, put the lens implant in, and before we open the wound we strip Descemet's," he said. "That's still done under a floored in- cision." Under viscoelastic he would then score Descemet's. "We like to do a descemetorhexis, where we start the tear of Descemet's mem- brane and then tear it as we do with a capsulorhexis," he said. "This prevents the peripheral tear of Descemet's beyond the size of the DSEK button." After stripping Descemet's, Dr. Holland removes all of the viscoelas- tic and then opens the incision to the desired 4.5- or 5-mm length. "We insert our DSEK button, close the wound, and establish the amount of air in the anterior cham- ber that we want," he said. "There are different techniques, but most surgeons will overfill the anterior chamber for the first few minutes and then after 5 or 10 minutes let some of the anterior chamber air out so they don't get a pupillary block- age during the post-operative pe- riod." Brief Summary of Prescribing Information PRESERVATIVE-FREE STERILE OPHTHALMIC SOLUTION in a Sterile Ophthalmic Unit Dose Dispenser TIMOPTIC ® 0.25% AND 0.5% (TIMOLOL MALEATE OPHTHALMIC SOLUTION) in OCUDOSE ® (DISPENSER) CONTRAINDICATIONS Preservative-free TIMOPTIC in OCUDOSE is contraindicated in patients with (1) bronchial asthma; (2) a history of bronchial asthma; (3) severe chronic obstructive pulmonary disease (see WARNINGS); (4) sinus bradycardia; (5 ) second or third degree atrioventricular block; (6) overt cardiac failure (see WARNINGS); (7) cardiogenic shock; or (8) hypersensitivity to any component of this product. WARNINGS As with many topically applied ophthalmic drugs, this drug is absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reacti ons, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported following systemic or ophthalmic administration of timolol maleate (see CONTRAINDICATIONS). Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. In Patients Without a History of Cardiac Failure continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, Preservative-free TIMOPTIC in OCUDOSE should be discontinued. Obstructive Pulmonary Disease Patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate severity, bronchospasti c disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma, in which TIMOPTIC in OCUDOSE is contraindicated [see CONTRAINDICATIONS]) should, in general, not receive beta-blockers, including Preservative-free TIMOPTIC in OCUDOSE. Major Surgery The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have experienced protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, some authorities recommend gradual w ithdrawal of beta-adrenergic receptor blocking agents. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists. Diabetes Mellitus Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergi c receptor blocking agents may mask the signs and symptoms of acute hypoglycemia. Thyrotoxicosis Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents that might precipitate a thyroid storm. PRECAUTIONS General Because of potential effects of beta-adrenergic blocking ag ents on blood pressure and pulse, these agents should be used with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of therapy with Preservative-free TIMOPTIC in OCUDOSE, alterna- tive therapy should be considered. Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppres- sant therapy (e.g. timolol). Angle-closure glaucoma: In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil. Timolol maleate has little or no effect on the pupil. TIMOPTIC in OCUDOSE should not be used alone in the treatment of angle-closure glaucoma. Anaphylaxis: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphy- lactic reactions. Muscle Weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been reported rarely to increase muscle weakness in some patients with myasthenia g ravis or myasthenic symptoms. Information for Patients Patients should be instructed about the use of Preservative-free TIMOPTIC in OCUDOSE. Since sterility cannot be maintained after the individual unit is opened, patients should be instructed to use the product immediately after opening, and to discard the individual unit and any remaining contents immediately after use. Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second or third degree atrioventricular block, or cardiac failure should be advised not to take this product. (See CONTRAINDICATIONS.) Drug Interactions Although TIMOPTIC (timolol maleate ophthalmic solution) used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with TIMOPTIC (timolol maleate ophthalmic solution) and epinephrine has been reported occasionally. Beta-adrenergic b locking agents: Patients who are receiving a beta-adrenergic blocking agent orally and Preservative-free TIMOPTIC in OCUDOSE should be observed for potential additive effects of betablockade, both systemic and on intraocular pressure. The concomitant use of two topical beta-adrenergic blocking agents is not recommended. Calcium antagonists: Caution should be used in the coadministration of beta-adrenergic blocking agents, such as Preservative-free TIMOPTI C in OCUDOSE, and oral or intravenous calcium antagonists, because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, coadministration should be avoided. Catecholamine-depleting drugs: Close observation of the patient is recommended when a beta blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additi ve effects and the production of hypotension and/or marked bradycardia, which may result in vertigo, syncope, or postural hypotension. Digitalis and calcium antagonists: The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time. CYP2D6 inhibitors: Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine, SSRIs) and timolol. Clonidine: Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. There have been no reports of exacerbation of rebound hypertension with ophthalmic timolol maleate. Injectable epinephrine: (See PRECAUTIONS, General, Anaphylaxis) Carcinogenesis, Mutagenesis, Impairment of Fertility In a two-year oral study o f timolol maleate administered orally to rats, there was a statistically significant increase in the incidence of adrenal pheochromocytomas in male rats administered 300 mg/kg/day (approximately 42,000 times the systemic exposure following the maximum recommended human ophthalmic dose). Similar differences were not observed in rats administered oral doses equivalent to approximately 14,000 times the maximum recommended human ophthalmic dose. In a lifetime or al study in mice, there were statistically significant increases in the incidence of benign and malignant pulmonary tumors, benign uterine polyps and mammary adenocarcinomas in female mice at 500 mg/kg/day (approximately 71,000 times the systemic exposure following the maximum recommended human ophthalmic dose), but not at 5 or 50 mg/kg/day (approximately 700 or 7,000 times, respectively, the systemic exposure following the maximum recommended human ophthalmic dose). In a subsequent study in female mice, in which postmortem examinations were limited to the uterus and the lungs, a statistically significant increase in the incidence of pulmonary tumors was again observed at 500 mg/kg/day. The increased occurrence of mammary adenocarcinomas was associated with elevations in serum prolactin which occurred in female mice administered oral timolol at 500 mg/kg/day, but not at doses of 5 or 50 mg/kg/day. An increased incidence of m ammary adenocarcinomas in rodents has been associated with administration of several other therapeutic agents that elevate serum prolactin, but no correlation between serum prolactin levels and mammary tumors has been established in humans. Furthermore, in adult human female subjects who received oral dosages of up to 60 mg of timolol maleate (the maximum recommended human oral dosage), there were no clinically meaningful changes in serum prolactin. Timolol malea te was devoid of mutagenic potential when tested in vivo (mouse) in the micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in vitro in a neoplastic cell transformation assay (up to 100 mcg/mL). In Ames tests the highest concentrations of timolol employed, 5,000 or 10,000 mcg/plate, were associated with statistically significant elevations of revertants observed with tester strain TA100 (in seven replicate assays), but not in the remaining three strain s. In the assays with tester strain TA100, no consistent dose response relationship was observed, and the ratio of test to control revertants did not reach 2. A ratio of 2 is usually considered the criterion for a positive Ames test. Reproduction and fertility studies in rats demonstrated no adverse effect on male or female fertility at doses up to 21,000 times the systemic exposure following the maximum recommended human ophthalmic dose. Pregnancy: Teratogenic Effects — Pregnancy Category C.: Teratogenicity studies with timolol in mice, rats and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose) demonstrated no evidence of fetal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (142,000 times the systemic exposure followi ng the maximum recommended human ophthalmic dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the maximum recommended human ophthalmic dose, in this case without apparent maternotoxicity. There are no adequate and well-controlled studies in pregnant women. Preservative-free TIMOPTIC in OCUDOSE should be used durin g pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers: Timolol maleate has been detected in human milk following oral and ophthalmic drug adminis- tration. Because of the potential for serious adverse reactions from timolol in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effective ness in pediatric patients have not been established. Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients. ADVERSE REACTIONS The most frequently reported adverse experiences have been burning and stinging upon instillation (approxi- mately one in eight patients). The following additional adverse experiences have been reported less frequently with ocular administration of this or other timolo l maleate formulations: BODY AS A WHOLE: Headache, asthenia/fatigue, and chest pain. CARDIOVASCULAR: Bradycardia, arrhythmia, hypotension, hypertension, syncope, heart block, cerebral vascular accident, cerebral ischemia, cardiac failure, worsening of angina pectoris, palpitation, cardiac arrest, pulmonary edema, edema, claudication, Raynaud's phenomenon, and cold hands and feet. DIGESTIVE: Nausea, diarrhea, dyspepsia, anorexia, and dry mouth. IMMUN OLOGIC: Systemic lupus erythematosus. NERVOUS SYSTEM/PSYCHIATRIC: Dizziness, increase in signs and symptoms of myasthenia gravis, paresthesia, somnolence, insomnia, nightmares, behavioral changes and psychic disturbances including depression, confusion, hallucinations, anxiety, disorientation, nervousness, and memory loss. SKIN: Alopecia and psoriasiform rash or exacerbation of psoriasis. HYPERSENSITIVITY: Signs and symptoms of systemic allergic reactions including anaphylaxis, angioedema, urticaria, and localized and generalized rash. RESPIRATORY: Bronchospasm (predominantly in patients with preexisting bronchospastic disease), respiratory failure, dyspnea, nasal congestion, cough and upper respiratory infections. ENDOCRINE: Masked symptoms of hypoglycemia in diabetic patients (see WARNINGS). SPECIAL SENSES: Signs and symptoms of ocular irritation including conjunctivitis, blepharitis, keratitis, ocular pain, discharge (e.g., crusting), foreign body sensation, itching and tearing, and dry eyes; ptosis; decreased corneal sensitivity; cystoid macular edema; visual disturbances including refractive changes and diplopia; pseudo- pemphigoid; choroidal detachment following filtration surgery (see PRECAUTIONS, General); and tinnitus. UROGENITAL: Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie's disease. The following additional adverse effects have been reported in clinical experience with ORAL timolol maleate or other ORAL beta blocking agents, and may be considered potential effects of ophthalmic timolol maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Body as a Whole: Extremity pain, decreased exercise tolerance, weight loss; Cardiovascular: Worsening of arterial insufficiency, vasodilatation ; Digestive: Gastrointestinal pain, hepatomegaly, vomiting, mesenteric arterial thrombo- sis, ischemic colitis; Hematologic: Non-thrombocytopenic purpura; thrombocytopenic purpura; agranulocytosis; Endocrine: Hyperglycemia, hypoglycemia; Skin: Pruritus, skin irritation, increased pigmentation, sweating; Musculoskeletal: Arthralgia; Nervous System/Psychiatric: Vertigo, local weakness, diminished concentration, reversible mental depressi on progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, emotional lability, slightly clouded sensorium, and decreased performance on neuropsycho- metrics; Respiratory: Rales, bronchial obstruction; Urogenital: Urination difficulties. Distributed by: Manufactured by: ATON Pharma, Laboratories Merck Sharp & Dohme-Chibret a Division of Valeant Pharmaceuticals North America LLC 63963 Clermont-Ferrand Cedex 9, France Madison, NJ 07940 Issued April 2009 © 2011, ATON Pharma All rights reserved. EyeWorld_IslandPI_PressReady.indd 1 2/23/11 8:55 PM Winning continued from page 92 February 2011 COMBINED SURGERY March 2011

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