Clinical Trials on Cataract and Refractive Surgery

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1 Clinical Trials: Cataract Clinical Trials: and Cataract Refractive and Refractive Surgery Clinical Trials on Cataract and Refractive Surgery Tarun Arora MD Tarun Arora MD, Vijay Kumar Sharma MS, Rajesh Sinha MD, Jeewan S. Titiyal MD Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi Infant Aphakia Treatment Study Infant Aphakia Treatment Study (IATS) is a multicenter, randomized, controlled clinical trial sponsored by the National Eye Institute. The objective of the study is to compare the use of primary IOL implantation to surgery without IOL implantation in infants with a unilateral congenital cataract removed between 1 and 6 months of age. Study Design: Inclusion criteria were a visually significant congenital cataract ( 3 mm central opacity) in one eye and an age of 28 days to less than 210 days at the time of cataract surgery. Infants with a unilateral cataract resulting from persistent fetal vasculature were allowed in the study as long as the persistent fetal vasculature was not associated with visible stretching of the ciliary processes or involvement of the retina or optic nerve. Exclusion criteria were an acquired cataract, a corneal diameter of less than 9 mm, and prematurity (36 gestational weeks). Randomisation to have either an IOL placed at the time of the initial surgery or to be left aphakic. Follow-up examinations were performed by an IATS certified investigator at 1 day, 1 week, 1 month, and 3 months after cataract surgery. Subsequent follow-up examinations were obtained at 3-month intervals. Surgical Technique: Infants randomized to the contact lens (CL) group underwent a lensectomy and anterior vitrectomy. Infants randomized to the IOL group had the lens contents aspirated followed by the implantation of an AcrySof SN60AT IOL into the capsular bag. In the event that both haptics could not be implanted into the capsular bag, an AcrySof MA60AC IOL was implanted into the ciliary sulcus. The IOL power was calculated based on the Holladay 1 formula targeting an 8-diopter (D) undercorrection for infants 4 to 6 weeks of age and a 6 D undercorrection for infants older than 6 weeks. After IOL placement, a posterior capsulectomy and an anterior vitrectomy were performed through the pars plana and plicata. When either a pre-existing opening was present or a rent developed during surgery in the posterior capsule and in some eyes with mild persistent fetal vasculature, the posterior capsulectomy and anterior vitrectomy were performed through the anterior incision before IOL implantation. Definitions for Intraoperative Complications (ICs) Definitions for ICs included unexpected difficulty or events occurring during the course of the surgery: (1) iris prolapse, or extrusion of the iris through the operative wound during surgery; (2) hyphema, or intraoperative bleeding that necessitated intraocular cautery or washout; (3) iris damage, or permanent structural change to the iris occurring during surgery; (4) retained cortex, or cortical material remaining in the eye after cataract surgery; (5) corneal clouding, or loss of corneal clarity occurring during the surgical procedure; (6) iris sphincterotomy, or intentional permanent enlargement of the pupil; (7) lens fragment in vitreous, or known loss of lens fragment into vitreous that was not retrieved; and (8) ruptured posterior capsule, or inadvertent rupture of the posterior capsule during the procedure. Definitions for Adverse Events (AEs) Glaucoma was defined as an IOP of more than 21 mmhg with one or more of the following anatomic changes: (1) corneal enlargement; (2) asymmetrical progressive myopic www. dosonline.org l 41

2 shift coupled with enlargement of the corneal diameter, axial length, or both; (3) increased optic nerve cupping defined as an increase of 0.2 or more in the cup-to-disc ratio; or (4) the use of a surgical procedure for IOP control. A patient was designated a glaucoma suspect if there was either: (1) two consecutive IOP measurements of more than 21 mmhg on different dates after topical corticosteroids had been discontinued without any of the anatomic changes listed above, or (2) glaucoma medications were used to control IOP without any of the anatomic changes listed above. Pupillary membrane was defined as fibrous tissue extending across the pupil. Lens reproliferation into the visual axis was defined as lens material regrowth extending into the pupillary space and interfering with vision. Children who had strabismus surgery were not classified as orthotropic, even if they later were shown to be orthotropic on motility testing. Other AEs that were encountered but do not require definition included the following: corectopia, vitreous hemorrhage, retinal hemorrhage, hyphema, retained cortex, retinal detachment, endophthalmitis, phthisis bulbi, keratitis, corneal abrasion, corneal opacity, corneal edema lasting more than 30 days, capsular phimosis, and wound leak or dehiscence. Definition for Additional Intraocular Surgery (AIS) AIS was defined as any return to the operating room for an intraocular surgery during the first postoperative year because of an AE or complication. Results Visual acuity The median logmar visual acuity was not significantly different between the treated eyes in the two groups (contact lens group, 0.80; IOL group, 0.97; P =.19). Intraoperative Complications There were more patients with ICs reported in the IOL group, 16 (21%), than the CL group, 6 (11%; P = 0.031). There were a total of 22 ICs in 16 IOL patients. Of these, iris prolapse was the most common (n = 12), followed by iris damage (n = 3), and hyphema (n = 2). There was one occurrence each of retained cortex, corneal clouding, iris sphincterotomy, lens fragment in the vitreous, and inadvertent rupture of the posterior capsule. In the CL group, 6 patients experienced 8 ICs: 3 with hyphema, 2 with iris prolapse, and 1 each with iris damage, retained cortex, and corneal clouding. Adverse Events In the first postoperative year, there were more patients with AEs in the IOL group, 44 (77%), than the CL group, 14 (25%;P<0.0001). The total number of AEs was 75 in the IOL group and 22 in the CL group. Fifty-two (69%) of the 75 AEs in the IOL group were related to the visual axis 24 cases of lens reproliferation, 17 cases of pupillary membranes, and 11 cases of corectopia versus only 2 such events in the CL group. The number of non visual axis-related AEs between the 2 groups was similar: 23 in the IOL group and 20 in the CL group. Severe complications associated with permanent visual loss retinal detachment, endophthalmitis, and phthisis were confined to the CL group. Glaucoma was diagnosed more often in the IOL group than the CL group 7 cases versus 3 cases although this did not reach statistical significance. Additional Intraocular Surgeries (AISs) More patients underwent AISs in the first 12 months after cataract surgery in the IOL group (n = 36) than the CL group (n = 7; P<0.0001). The total number of surgeries in the IOL group (n = 43) also was significantly higher than the CL group (n = 11). Looked at another way, only 13% of CL patients required AIS in the first 12 months, whereas 63% of the IOL group required an additional surgery. Most additional surgeries in both groups were necessary to clear visual axis opacities: 34 of the 43 in the IOL group and 6 of 11 in the CL group. Four patients in the IOL group underwent surgery for glaucoma versus 1 patient in the CL group. IOL Power and placement The mean power (±SD) of the implanted IOL was 29.9 (5.7) D overall (31.5 [5.0] D for the younger age group and 28.7 [6.0] D for the older age group); IOL power range was 11.5 to 40.0 D. Twenty-five eyes were implanted with an IOL with a power of 30.0 D or greater and 10 of these were implanted with an IOL with a power of 35.0 D or greater. In 46 patients (94%), the IOL was placed within the capsular bag. Ciliary sulcus IOL placement was performed for 1 patient in the younger age group and 2 patients in the older age group. Follow-up Refraction and Prediction Error (PE) The overall mean (±SD) refraction at 1 month was +6.1 (2.0) D. The mean refraction was +6.6 (1.9) D in the younger age group and +5.7 (1.9) D in the older age group. Twenty-two eyes (45%) achieved a postoperative refraction within 1.0 D of the target refraction of +8.0 D or +6.0 D outlined by the IATS protocol. A relatively large PE is common when performing IOL implantation in infant eyes, especially with the shortest axial lengths (<18 mm), even when using a formula designed for short eyes. Conclusion At 1 year after surgery, there have been more ICs, AEs, and need for AISs in the IOL group compared with the CL 42 l DOS Times - Vol. 19, No. 10 April, 2014

3 group. These differences between the 2 groups have not been associated with a worse visual outcome to date. There is reason to believe that, over the long term, the number of AISs between the 2 groups will become more even. 1. Lambert SR, Lynn MJ, DuBois LG, et al. Infant Aphakia Treatment Study Groups. Axial elongation following cataract surgery during the first year of life in the infant Aphakia Treatment Study. Invest Ophthalmol Vis Sci. 2012;53: Carrigan AK, DuBois LG, Becker ER, et al. Infant Aphakia Treatment Study Group. Cost of intraocular lens versus contact lens treatment after unilateral congenital cataract surgery: retrospective analysis at age 1 year. Ophthalmol. 2013;120: Drews-Botsch CD, Celano M, Kruger S, et al. Infant Aphakia Treatment Study. Adherence to occlusion therapy in the first six months of follow-up and visual acuity among participants in the Infant Aphakia Treatment Study (IATS). Invest Ophthalmol. Vis Sci. 2012;53: VanderVeen DK, Nizam A, Lynn MJ, et al. Infant Aphakia Treatment Study Group. Predictability of intraocular lens calculation and early refractive status: the Infant Aphakia Treatment Study. Arch Ophthalmol. 2012;130: Beck AD, Freedman SF, Lynn MJ, et al. Infant Aphakia Treatment Study Group. Glaucoma-related adverse events in the Infant Aphakia Treatment Study: 1-year results. Arch Ophthalmol. 2012;130: Postoperative endophthalmitis: ESCRS study Purpose To identify risk factors and describe the effects of antibiotic prophylaxis on the incidence of postoperative endophthalmitis after cataract surgery based on analysis of the findings of the European Society of Cataract & Refractive Surgeons (ESCRS) multicenter study. Study Design All patients taking part in the study had phacoemulsification cataract surgery with placement of an intraocular lens (IOL) as a single procedure without additional surgery. All operations took place within a modern operating room with assisted ventilation and full sterile and aseptic techniques. Each patient gave informed consent and was supplied with an information sheet in his or her own language. Twentyfour hospitals took part in the study, based in 9 countries: Austria (1), Belgium (5), Germany (1), Italy (2), Poland (1), Portugal (1), Spain (4), Turkey (1), and the United Kingdom (8). The study was planned as a factorial design to test for the effects of 2 prophylactic interventions: (1) cefuroxime injected into the anterior chamber at the end of surgery as 1 mg in 0.1 ml normal saline, and (2) levofloxacin 0.5% administered 1 drop 1 hour before surgery, 1 drop 30 minutes before surgery, and 3 drops at 5-minute intervals commencing immediately after surgery. The patients were randomly assigned to 1 of 4 treatment groups of approximately equal sizes. Group A received no perioperative antibiotic prophylaxis, Group B received the intracameral cefuroxime treatment only, Group C received the topical levofloxacin treatment only, and Group D received both intracameral cefuroxime and topical levofloxacin treatments. The levofloxacin treatment was masked; with patients receiving placebo or antibiotic drops from bottles supplied as part of the study. The use of cefuroxime was not masked; surgeons were requested to give patients who had been randomly allocated to Groups B and D the intracameral injection at the end of surgery. All patients received povidone iodine 5% drops (Betadine) into the conjunctival sac and onto the cornea for a minimum of 3 minutes before surgery, and all patients were requested to use levofloxacin 0.5% eyedrops (Oftaquix) 4 times daily for 6 days starting the day after surgery. Case Definition Clinicians were alert for the signs and symptoms associated with endophthalmitis. A diagnosis of presumed endophthalmitis was made for any patient presenting with pain or loss of vision thought to be due to infection. Samples of aqueous and vitreous were collected from these patients and investigated using Gram staining, culture, and polymerase chain reaction testing using nonspecific microbial primers. Any case in which at least one of these tests yielded a positive result was classified as proven infective endophthalmitis. The total endophthalmitis cases constituted these proven cases together with those identified by the clinicians but for which no positive proof of infection was found. Each unproven case was reviewed for evidence of toxic anterior segment syndrome (TASS) or noninfective uveitis. Based on these case definitions, separate analyses of the study data were performed on (1) total endophthalmitis cases (including both the proven and unproven cases), and (2) proven infective endophthalmitis cases only. Cases of Endophthalmitis Within the Study and Incidence Rates Highest incidence rates were in Group A (placebo drops, no intracameral injection), where the observed rate for total endophthalmitis was 0.345% and for proven endophthalmitis, 0.247%.The lowest observed incidence rates were in Group D, which received both the intracameral cefuroxime and perioperative topical levofloxacin. These rates were 0.049% for total endophthalmitis and 0.025% for proven endophthalmitis. When this study began, the only proven method of prophylaxis against infective endophthalmitis after cataract surgery was the administration of povidone iodine preoperatively. The use of postoperative antibiotic drops was also considered to be of benefit. The results in this study indicate that for patients in Europe for whom these are the only methods of prophylaxis used, the incidence of total www. dosonline.org l 43

4 endophthalmitis is centered on a rate as high as 0.35%. This may be regarded as high for a background rate; however, rates reported in other studies have often been for patients receiving various additional forms ofprophylaxis, some of which have, no doubt, been of benefit. The results presented here also indicate that with the prophylactic use of intracameral cefuroxime, the incidence rate can be reduced to a level below 0.08%. In addition to the administration of intracameral cefuroxime at the time of surgery, other important factors associated with a reduction in the risk for endophthalmitis were the use of acrylic material for the IOL optic and the choice of scleral tunnel as the site of incision. The finding that silicone as the IOL optic material was associated with a significantly increased risk for endophthalmitis (between 3- and 4-fold) is of particular interest because this factor is clearly under the control of the clinician. It has been suggested that the apparent increased risk for endophthalmitis incurred by the use of silicone as the IOL optic material may be due to the hydrophobic nature of silicone. The currently popular clear corneal incision (CCI) was found to be associated with a significantly higher risk for endophthalmitis, a result supported by other recent findings. However, there was no evidence in the current study to support the hypothesis that temporal incision placement was associated with an increased risk. Although the risk associated with CCIs remains an important finding in this study, the result must be treated with caution. Only two participating centers used scleral tunnel incisions routinely, with none of the others using it more than occasionally. It is therefore conceivable that the reduced risk associated with the scleral tunnel technique is due to some other unidentified factor common to both centers but absent from most other centers in the study. Conclusion In summary, the results clearly show that endophthalmitis is a multifactorial problem with associations to risk factors that depend on the attributes of the patient, the clinician, the antibiotic treatment, the surgical procedure, and the IOL materials used. Introduction of perioperative intracameral cefuroxime in cataract surgery across Europe could reduce the number of endophthalmitis infections by approximately cases over the coming decade. If the additional factors identified are causes of increased risk, avoidance of silicone IOLs and the use of a scleral tunnel incision rather than a CCI would result in an even more marked reduction. 1. Barry, P., Seal, D. V., Gettinby, et al. ESCRS study of prophylaxis of post-operative endophthalmitis after cataract surgery: Preliminary report of principal results from a European multi-centre study. J Cataract Refract Surg. 2006; 32: Bucci, F. A.: An In Vivo Study Comparing the Ocular Absorption of Levofloxacin and Ciprofloxacin Prior to Phacoemulsification. Am J Ophthalmol. 2004;137: Colin, J., Simonpoli, S., Geldsetzer, K., et al. Corneal penetration of levofloxacin into the human aqueous humour: a comparison with ciprofloxacin. Acta Ophthalmol Scand. 2003;81: Doft, B. H., Wisniewski, S. R., Kelsey, S. F., et al. Endophthalmitis Vitrectomy Study Group: Diabetes and postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study. Arch Ophthalmol. 2001;119: ESCRS Endophthalmitis Study Group: Prophylaxis of post-operative endophthalmitis following cataract surgery: results of the ESCRS multi-centre study and identification of risk factors. J Cataract Refract Surg. 2007;33: Excimer laser refractive surgery versus Phakic IOL for the correction of moderate to high myopia: Cochrane Review Objectives The objectives of this review were to compare excimer laser refractive surgery and phakic IOLs for the correction of moderate to high myopia by evaluating postoperative uncorrected visual acuity, refractive outcome, potential loss of best spectacle corrected visual acuity (BSCVA) and the incidence of adverse outcomes. Selection criteria It included randomised controlled trials (RCTs) comparing excimer laser refractive surgery and phakic IOLs for the correction of myopia greater than 6.0 diopters (D) spherical equivalent. Main results This review included three RCTs with a total of 228 eyes. The range of myopia of included patients was -6.0 D to D of myopia with up to 4.0 D of myopic astigmatism. The percentage of eyes with uncorrected visual acuity (UCVA) of 20/20 or better at 12 months postoperative was not significantly different between the two groups. Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12 months postoperatively. However there is a low risk of developing early cataract with phakic IOLs. Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL surgery also scored more highly on patient satisfaction/preference questionnaire. Summary of main results The percentage of eyes with UCVA of 20/20 or better at 12 months postoperatively was not significantly different between the two groups. Phakic IOL surgery is safer than excimer laser surgical correction for moderate to high myopia. It results in significantly less final loss of BSCVA. 44 l DOS Times - Vol. 19, No. 10 April, 2014

5 There is a low risk of developing early cataract with phakic IOLs. Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL surgery also scores more highly on patient satisfaction/preference questionnaires. 1. El Danasoury MA, El Maghraby A, Gamali TO. Comparison of iris-fixed Artisan lens implantation with excimer laser in situ keratomileusis in correcting myopia between and diopters: a randomized study. Ophthalmology 2002;109: Malecaze FJ, Hulin H, Bierer P, et al. A randomized paired eye comparison of two techniques for treating moderately high myopia: LASIK and artisan phakic lens. Ophthalmology 2002;109: Schallhorn S, Tanzer D, Sanders DR, Sanders ML. Randomized prospective comparison of visian toric implantable collamer lens and conventional photorefractive keratectomy for moderate to high myopic astigmatism. Journal of Refractive Surgery 2007;23: Monthly Clinical Meeting, July 2014 Venue: Ground and Ist Floor VMMC Building, Vardhman Mahavir Medical College and Safdarjang Hospital Date: 27 th July, 2014 (Sunday) Clinical Session: 11:00 a.m. onwards Delhi Ophthalmological Society Breakfast & Registration: 10:00 a.m. Onwards Clinical Cases: 1. Multifocal basal cell carcinoma : Dr. Myuresh 10 mins. Discussant : Dr. Anuj Mehta 2. Isolated superior ophthalmic vein thrombosis : Dr. Neha Mehrotra 10 mins. Discussant : Dr. Sangeeta Abrol Guest Case Presentation from: Shroff Charity Eye Hospital, Darya Ganj, New Delhi Combined vascular occlusion : Rahul Mayor 10 mins. Clinical Talk: Post operative endophthalmitis: Prophylaxis and Management : Prof. B.P. Guliani 15 mins. Mini Symposium: Ophthalmic debates Chairperson: Prof. V.S. Gupta, Co-Chairperson: Prof. L. Sarkar 1. Conventional phaco vs. Femto cataract surgery : Dr. Harinder Sethi & 5 mins. : Dr. Ritika Sachdev 5 mins. 2. Shunt surgery - future for open angle glaucoma for & against : Dr. Harsh Kumar & 5 mins. Prof. V.S. Gupta 5 mins. 3. Fascia lata vs. Silicone rod in sling surgery : Prof. V.P. Gupta & 5 mins. Dr. Anuj Mehta 5 mins. 20 early bird prizes will be given www. dosonline.org l 45