As cataract surgical techniques and related technologies improve, the demand for higher-quality cataract surgery may actually increase along with them. Fortunately, research and product development are helping us keep pace. Here are some of the notable efforts this year; unless otherwise noted, these studies were not commercially funded.

 


Drug Issues


Following recent years' increased use of Kenalog (intravitreal triamcinolone) for retinal diseases and noting that cataract formation is one of the potential complications, researchers in Tunisia sought to gather long-term data on its incidence.


They studied 79 phakic eyes of 70 patients who underwent IVTA (4 mg) and completed at least 12 months' follow-up. Indications for triamcinolone injection included severe macular edema of various causes and choroidal neovascularization associated with age-related macular degeneration. Seventy-three eyes received one injection, and the six remaining eyes, two injections. Mean follow-up was 20 months (range, 12 to 48).


Significant progression of cataract occurred in 51 eyes (64.6 percent), significant elevation of intraocular pressure in 18 eyes (22.8 percent), pseudoendophthalmitis in three eyes (3.8 percent), and retinal detachment in one eye (1.3 percent). No case of endophthalmitis was recorded. Mean time to IOP elevation was one month and to cataract formation, 13 months. Cataract surgery was performed in 35 eyes (44.3 percent) and was uneventful in all cases. Of 18 eyes with significant IOP elevation, 17 (94.4 percent) were managed with topical glaucoma medication and only one eye (5.6 percent) required a trabeculectomy. The three pseudoendophthalmitis  cases were managed with medical treatment and the retinal detachment was successfully treated with vitrectomy.269


More recently, bevacizumab (Avastin) has become an off-label treatment of choice for a host of refractory retinal conditions. A group at the University of Texas, San Antonio, points out that the drug's potential for intraocular toxicity has focused on retinal cells, but anterior segment cell-types would also be susceptible to any adverse drug effects. They sought to determine Avastin's effect on human lens epithelial cells.


They exposed human-derived lens epithelial cells to Avastin at a concentration of 0.0156 mg/mL for 16 hours. This concentration was chosen to approximate the concentration of a commonly used 1.25-mg dose of Avastin in 0.05 mL after injection into a 4 ml vitreous cavity. A 0.05-mL dose of Avastin was diluted with 4 mL of warmed cell media and placed in a culture plate containing the cells. Control cells were exposed to an equal volume of untreated media. The cells were incubated overnight. Cell viability was assessed using the MTT cell viability assay. After 60 minutes' incubation, absorbance values at 570 nm were measured and compared.


The Avastin-treated group absorbed at 0.157 optical density, while that of the control group was 0.145 OD. This difference was statistically significant. No significant toxicity was found. Rather, cells exposed to Avastin had somewhat better viability outcomes, which the group says may reflect other cellular effects of Avastin, such as stimulation of growth rate. Additional assays at varying concentrations and exposure times are planned to identify other effects of Avastin on these cells. The present results, however, indicate that Avastin does not have negative effects on human lens epithelial cell viability, at least in the short term.
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Post-Cataract CME


What predicts clinically significant macular edema following cataract surgery? Numerous anecdotal risk factors have been proposed, but no evidence-based studies exist, say Canadian researchers. To identify predictors in patients with and without glaucoma, they conducted a retrospective review of 697 patient files in a glaucoma practice at a tertiary-care setting in London, Ontario. The rate of CME was 1.3 percent for the entire data set and 2.3 percent for the glaucoma-medication subgroup. For the entire data set, multivariate analysis found four variables to be strongly associated with clinically significant CME (p=0.05). These independent predictors, with their adjusted odds ratio:


1. Preop topical fixed combination beta-blocker and carbonic anhydrase inhibitor (i.e. Cosopt)—OR 10.7


2. Intraoperative pupil stretching—OR 20.4


3. Intraoperative PMMA intraocular lens implant—OR 65.7


4. Postop topical prostaglandin—OR 8.5


Based upon these predictors, they derived a scoring system to determine absolute risk and risk level (i.e. low, moderate, and high risk). For the glaucoma medication subgroup, two variables that were strongly associated with clinically significant CME:


1. Preoperative topical fixed combination beta-blocker & carbonic anhydrase inhibitor (i.e. Cosopt)—OR 6.9


2. Intraoperative pupil stretching—OR 14.7.5462


Another group, this one at UCLA's Jules Stein Institute, also examined the incidence of and risk factors for developing CME following cataract surgery in glaucoma patients. Their study included 862 patients (eyes) with glaucoma and 391 patients (eyes) without glaucoma or with suspicion of glaucoma who underwent cataract surgery over an eight-year period. CME was diagnosed clinically by fundus examination with decrease of visual acuity at the four to eight week postoperative visit. Risk factors for CME were determined with a logistic regression model comparing patients who did and did not develop CME after cataract surgery.


The incidence of CME in glaucoma was 5.34 percent and in non-glaucoma patients was 5.63 percent (p=0.76). Patients who developed CME (68 patients) had statistically higher rates of anterior vitrectomy and/or anterior chamber intraocular lens implantation due to rupture of posterior capsule during surgery (8.8 vs. 2.9 percent, p=0.010), using topical bimatoprost before the surgery (10.3 vs. 4.1 percent, p=0.019) and using topical betaxolol after the surgery (2.9 vs. 0.5 percent, p=0.031), compared to patients who did not develop CME (1,185 patients).


There is, they conclude, no statistically significant difference in the incidence of CME following cataract surgery between glaucoma and non-glaucoma patients. The use of certain topical anti-glaucoma drops before or after cataract surgery and anterior vitrectomy required during cataract surgery are potential risk factors for developing CME after cataract surgery.5461


An Allergan-affiliated group suggests that retinal thickening of >10 µm (sub-clinical CME) affects visual quality, even in low-risk cataract patients, and that the incidence of sub-clinical CME and CME is reduced by NSAID and steroid treatment versus steroid alone.


The investigator-masked, multicenter clinical trial randomized 546 low-risk patients undergoing cataract surgery to two groups in a 1:1 ratio: Group 1 received ketorolac 0.4% q.i.d. for three days prior to surgery and four doses during dilation immediately before the procedure. These patients used ketorolac q.i.d. until they exited the study and also instilled prednisolone q.i.d. from a 5-ml bottle until empty. Group 2 received a tear solution for three days prior to surgery and only four doses of ketorolac 0.4% during dilation immediately before the procedure. These patients continued to use the tear solution q.i.d. until the bottle was empty and instilled prednisolone q.i.d. from two 5-ml bottles until exiting the study. Follow-up study visits were on day one, week one and week four, with retinal thickening measured by OCT at preop and weeks one and four.


Use of ketorolac 0.4% significantly reduced the incidence of retinal thickening and CME. Table 1 below lists the comparison of the two groups.



Group 2 patients (2.4 percent) were also significantly more likely than Group 1 patients (0 percent) to have CME as diagnosed by a masked retinal specialist, p=.018. Patients with <10 µm of thickening had significantly better contrast sensitivity scores at 6, 12 and 18 cpd than patients with >10 µm of thickening (p<.032). There was also a trend toward worsening visual acuity with increased retinal thickening (p=.085).5464


A larger study, this one by multiple investigators in Boston, some affiliated with Alcon, set out to characterize the incidence, duration, risk factors for and outcome of post-cataract CME in non-diabetic patients. Over a five-year period, 1,659 consecutive cataract surgeries were classified into two groups according to presence of CME, whose diagnosis required both worsening of vision and fundoscopic, fluorescein angiographic or OCT evidence. Diabetics were excluded due to the potential difficulty of differentiating CME from clinically significant macular edema. The overall incidence of postoperative CME was 2.4 percent (39/1,659) and 2.1 percent (29/1,357) when diabetic patients were excluded.


Three factors were predictive of postop CME: history of retinal vein occlusion (OR 31.75, p<.001); epiretinal membrane (OR 4.93, p<.03); and preoperative prostaglandin use (OR 12.45, p<.04). Patients who have known increased risk factors for CME (diabetes and intraoperative complications) did not have an increased risk when treated with prophylactic postoperative NSAIDs for at least one to three months.


The group suggest that treating patients with a higher risk of developing CME with topical NSAIDs after cataract surgery appears to decrease risk of postoperative CME.
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Intraocular Lenses


Two University of California-Davis, researchers point out that one effect of the apodized rings in multifocal apodized ReSTOR IOL (Alcon) is to create larger laser spot sizes than expected, especially when increasing the intensity or duration of the laser. This may have clinical significance when performing macular laser or laser that requires a long beam duration as in the case of a photodynamic therapy laser.


The pair constructed an experimental optical bench using an IOL mount attached to an adjustable rail. They directed a 635-nm laser through either an SN60AT monofocal IOL or a ReSTOR IOL of similar power. The resulting laser beam spot size and intensity were derived from these digital images, and a comparison was made between images produced by the two lenses. Several variables, e.g., intensity, duration and size and/or position of the laser beam, were analyzed to assess their effect on the resulting laser beam spot size. The laser spot size generated by the ReSTOR IOL varies depending on where the laser hits the IOL, and the variation in laser spot size is greater with larger laser beam sizes.


The results may also help to improve the understanding of the clinical effect of increased halos reported by patients with multifocal IOLs. In vivo data is needed to obtain the true difference in spot size created by the ReSTOR lens.118


A group at the University of Rome, Italy, compared visual acuity and contrast sensitivity in the ReStor and the Acrysof Sa60AT monofocal IOL.


They implanted the ReStor in the capsular bag in 50 patients (100 eyes) undergoing cataract surgery. Inclusion criteria were corneal astigmatism <1.5 D, myopia <6 D, and no associated ocular disease. UCVA, BCVA and contrast sensitivity were measured at 60 days postoperatively. Results were compared with those obtained from 10 patients (20 eyes) implanted with AcrySof monofocal IOLs.


In the multifocal group 86 eyes' distance UCVA was 20/20 or better (logMAR <0.04) and near UCVA at the standard distance of 33 cm was 20/25 or better (logMAR 0.14). Distance UCVA and BCVA in the ReSTOR group were not statistically different from the monofocal group, but near UCVA was statistically better in the multifocal group, with 98 percent of the ReStor patients reporting total spectacle independence. Contrast sensitivity was reduced in the multifocal group compared with the monofocal group, and 9 percent of the ReSTOR patients reported halos and glare.5422


An independent study in Amiens, France compared visual results and quality of vision in 36 cataract patients, all with corneal astigmatism of less than 1 D, implanted with ReZoom (AMO) or the ReStor. Evaluation of visual results was performed between the first and the third postoperative month, and the quality of vision was assessed by a questionnaire dealing with patient satisfaction, presence of halos and glare.


The average age of the 18 patients in the ReZoom group was 66 years old; in the ReSTOR group, it was 69. Both groups had good uncorrected distance VA postoperatively: 65 percent (ReZoom) and 85 percent (ReSTOR) recuperated 0.1 logMAR or better. Uncorrected near visual acuity was excellent: 81 percent (ReZoom) and 84 percent (ReSTOR) were able to read 0.3 logMAR. Halos and glare were noted by 20 percent in the ReZoom group and 11 percent in the ReSTOR group. All of these patients seemed to tolerate this discomfort, and 100 percent of the patients in both groups were satisfied with the results of their surgeries.
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Surgical Issues


Patients should be informed of the risk of mild eyelid ptosis as a possible complication of cataract surgery, according to a University of Florida, Gainesville, study. Researchers there retrospectively reviewed the records of patients undergoing phacoemulsification, evaluating eyelid parameters including horizontal fissure height (HFH), vertical fissure height (VFH), marginal reflex distance one (MRD1) and two (MRD2), levator function (LF), and upper lid crease distance (ULC). These parameters were analyzed preoperatively, on postoperative days one, seven and 30. The non-operative eye served as the control. Operative variables included type of surgery, duration of surgery, type of eyelid speculum, type of drape, method of removal of drape, use of retrobulbar block, use of bridal suture, and use of postoperative patching. Prior eyelid surgery in either eye and absence of complete eyelid parameter data were the main exclusion criteria.


Data analysis demonstrated a 1.1-mm average decrease in MRD1 (p=0.001), a 1.4-mm average decrease in VFH (p=0.004), and a corresponding 0.4-mm increase in ULC (p=0.004) when comparing eyelid parameters between the preoperative and postop day one visits. MRD1 increased by an average of 0.35 mm (p=0.005) with a corresponding average increase of 0.46 (p=0.01) in VFH between postop days seven and 30. When comparing the preop and postop day 30 eyelid parameters, the only statistically significant change was an average decrease of 0.7 mm in MRD1 (p=0.01, range, zero to 2.5 mm). Trace ptosis (<1 mm) was noted in seven of the 23 cases, and two patients showed mild ptosis (1 mm to 2.5 mm) when comparing  postop day 30 to preop.575


Adults with a history of premature birth tend to have cataract surgery at a young age, with a mixed range of visual results, and high rates of retinal complications, say surgeons at Philadelphia's Wills Eye Hospital and Beaumont Eye Institute, Royal Oak, Mich. They retrospectively reviewed the charts of 66 eyes from 45 such patients who underwent cataract surgery. The cases were followed for up to 38 years (median 9.9 years). Thirty-seven eyes (56 percent) had minimal cicatricial changes from retinopathy of prematurity. The mean age of cataract surgery was 40.3 years. Twenty-five eyes (38 percent) had at least a one-line improvement in vision, 20 eyes (30 percent) had no change in vision, and 21 eyes (32 percent) had a decline in vision after cataract surgery. A postoperative complication of a retinal tear or retinal detachment developed in 15 of the 66 eyes (23 percent). The severity of the baseline fundus changes from ROP did not correlate with the likelihood of developing a post-cataract surgery complication.
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Patient Care


Cataract patients may be unnecessarily restricting their postop activities, according to a British study. Surgeons at two London hospitals became aware of this possibility, investigated its extent and tested interventions designed to improve postoperative activity.


After routine first-eye cataract surgery, three groups of 50 patients completed a questionnaire asking if they had avoided specific activities in the three weeks between surgery and review, and if so, why. One group received standard discharge instructions telling them that they could continue specified activities, such as bending, face-washing, hair-washing, cooking, cleaning, exercising and watching TV. A second group received an additional written sheet specifying safe activities. The third group received a sheet with photographs of people performing safe activities.


Sixty-four percent of standard-instruction patients reported avoiding one or more of the activities; 44 percent of the written-instruction group did so; and 30 percent of the photo groups reported doing so. In all groups, more than 50 percent of patients said they had avoided activities on their own volition, not because they had been advised not to.1054


Another group in the UK tested a different hypothesis on retention of instruction, this one focusing on audio, to determine the percentage of knowledge retained following a preoperative assessment and whether any improvement in that knowledge occurred after an audio tape recording of the consultation was provided.




In the first of a two-part study, 82 patients undergoing cataract surgery were given verbal and written explanations about cataract surgery. In the second part, 56 other patients received an audio recording of the entire preoperative assessment interview with instructions to listen to the tape at home. The information recall in both groups was checked by questionnaire.


The overall recall of correct information was 40 percent in the first part of study. In the second part, information recall improved (p<0.01) and was found to be 64.7 percent in the first-eye group and 70.8 percent in the second-eye group among the female patients. Male patients had a higher recall in the first eye group (71.9 percent) and a lower recall in the second (60.2 percent).1053


 

Endophthalmitis Updates


The 2006 ESCRS Endophthalmitis Study confirmed the role of intracameral cefuroxime in preventing intraocular infection. But the drug is not labeled for this use and not available in a commercial formulation in the United States. Researchers at the University of Pittsburgh compared the in vitro susceptibility of cefuroxime, a second-generation cephalosporin, to moxifloxacin, gatifloxacin and cefazolin, a first-generation cephalosporin.


The in vitro susceptibility profiles for the four antibiotics were statistically equivalent for Staphylococcus aureus (n=14), Coagulase-negative Staphylococcus (n=20), Streptococcus pneumoniae (n=10), St. viridans (n=10), Beta-hemolytic streptococcus (n=5), and Haemophilus (n=4). Moxifloxacin and gatifloxacin provided higher susceptibility to Bacillus (n=9), Enterococcus (n=9), and Gram-negative bacteria (n=11) than cefuroxime and cefazolin. Against all isolates, the in vitro susceptibility profiles of cefuroxime and cefazolin were equivalent.


Based on in vitro susceptibility testing using actual endophthalmitis isolates, moxifloxacin and gatifloxacin provide wider antibacterial coverage than cefuroxime or cefazolin, they conclude. While the debate over the efficacy of intracameral antibiotics for the prophylaxis of postoperative endophthalmitis continues, fourth-generation fluoroquinolones may provide more broad spectrum coverage of endophthalmitis-causing bacteria than cefuroxime.775


On the intracameral endophthalmitis prophylaxis issue, an Iowa researcher affiliated with both AMO and Alcon assessed the safety of self-preserved intracameral moxifloxacin (Vigamox, Allergan) at the conclusion of routine cataract surgery, including its effect on corneal status, visual acuity and anterior chamber reaction.


A total of 200 consecutive cataract procedures with intracameral moxifloxacin were included (53 male, 88 females, mean age 71, range, 27 to 94 years). Outcomes were compared with consecutive historical control patients (n=100) who had similar demographic characteristics but did not receive intracameral moxifloxacin. At day one postop, four (2 percent) of treated eyes had aqueous cell counts of 3+ or more, compared to 11 (11 percent) of eyes in the control group (p=0.0007).


At one week postop, 95 percent of the treated group had none or trace cells compared to 96 percent of controls (p=0.6987) Similarly, 5 percent in the treated group had 1+ cells and 4 percent the control group had 2+ cells. No postop epithelial defect or stromal edema was observed in the treated group. Visual acuity was not comparable between groups at baseline and prevented a valid comparison. Both groups, however, were approximately 20/25 one week postop.


The author concludes that employing this readily available, broad-spectrum, potent antibiotic in this highly bioavailable form may increase the safety of cataract surgery.
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Dr. Blecher, Review's chief medical editor, is co-director of the Cataract Department at the Wills Eye Hospital, in Philadelphia.